Effect of anthrax immune globulin on response to BioThrax (anthrax vaccine adsorbed) in New Zealand white rabbits.

PubMed

Malkevich, Nina V; Basu, Subhendu; Rudge, Thomas L; Clement, Kristin H; Chakrabarti, Ajoy C; Aimes, Ronald T; Nabors, Gary S; Skiadopoulos, Mario H; Ionin, Boris

2013-11-01

Development of anthrax countermeasures that may be used concomitantly in a postexposure setting requires an understanding of the interaction between these products. Anthrax immune globulin intravenous (AIGIV) is a candidate immunotherapeutic that contains neutralizing antibodies against protective antigen (PA), a component of anthrax toxins. We evaluated the interaction between AIGIV and BioThrax (anthrax vaccine adsorbed) in rabbits. While pharmacokinetics of AIGIV were not altered by vaccination, the vaccine-induced immune response was abrogated in AIGIV-treated animals.

WinRho: Rh immune globulin prepared by ion exchange for intravenous use.

PubMed Central

Bowman, J M; Friesen, A D; Pollock, J M; Taylor, W E

1980-01-01

An Rh immune globulin [Rh IgG] for intravenous use, WinRho, has been prepared by the Winnipeg Rh Institute by a modification of the ion-exchange column method of Hoppe and colleagues. When administered to Rh-negative male and nonpregnant female volunteers WinRho was found to be nonpyrogenic, nontoxic, safe and protective against Rh alloimmunization. In a clinical trial with 240 microgram given at about 28 weeks' gestation and 120 microgram given after delivery to Rh-negative women at risk of Rh immunization WinRho was effective in preventing Rh immunization. Of the 870 women carrying Rh-positive fetuses who were treated with WinRho during pregnancy and were not tested several months after delivery 14 would have shown evidence of Rh immunization by the time of delivery if WinRho had been ineffective; none showed such evidence. Of the 1122 women carrying Rh-positive fetuses who were retested 4 to 6 months after delivery 83 would have shown evidence of Rh immunization at that time if WinRho had been ineffective; only 1 showed such evidence. The efficiency of yield of anti-D with the modified method of production, the fct that it can be given intravenously (a route that causes the patient less discomfort and immediately results in high anti-D levels) and the lower levels of contaminating IgA and IgM make WinRho the preparation of choice for preventing Rh immunization. PMID:6161687

Antigenic Structure of Rabbit γ Globulin

PubMed Central

Dubiski, S.; Dubiska, Anna; Skalba, Danuta; Kelus, A.

1961-01-01

By iso-immunization, antisera to five rabbit γ globulin antigens were obtained. They are called A (former Da), B, C, D and E. Individual sera of 670 rabbits belonging to six separate populations were tested by precipitation methods. The distribution of the iso-antigens and their combinations into serum groups were studied. Each particular γ globulin iso-antigen was found to be of hereditary character; they seem to form three genetic systems: A, C and BDE, statistically independent. Various antisera from England, Poland and U.S.A were compared. PMID:13724581

Immune reconstitution with two different rabbit polyclonal anti-thymocytes globulins.

PubMed

Bamoulid, Jamal; Crepin, Thomas; Gaiffe, Emilie; Laheurte, Caroline; Moulin, Bruno; Frimat, Luc; Rieu, Philippe; Mousson, Christiane; Durrbach, Antoine; Heng, Anne-Elisabeth; Rebibou, Jean-Michel; Saas, Philippe; Courivaud, Cécile; Ducloux, Didier

2017-12-01

Broad T cell depletion by polyclonal anti-thymocyte globulins (ATG) has been used for many years as a part of immunosuppressive treatment in transplantation. Currently, two different ATG are used in clinical practice, Thymoglobulin and Grafalon. Due to differences in the immunization source, these products contain different specificities and quantity of antibodies. These differences may have clinical consequences. We conducted a nested study in a large prospective multicentric cohort of kidney transplant to determine whether Grafalon-treated and Thymoglobulin-treated patients experience different lymphocyte reconstitution and clinical outcomes. 182 patients matched for age, gender, CMV status, CMV prophylaxis, number of previous transplantation, and maintenance immunosuppressive treatment were included (Thymoglobulin, [n=91]; Grafalon®, [n=91]). One-year post-transplant, recent thymic emigrants were significantly decreased (12±10% vs 21±12%; p<0.001) in Grafalon-treated patients. By contrast, T cell activation (CD38+DR+Ki67+) and senescence (CD8+CD57+CD28-) was increased in Thymoglobulin-treated patients. Compared to Grafalon, Thymoglobulin was not associated with a significantly different rate of acute rejection. CMV disease (p=0.013) was more frequent in Thymoglobulin-treated patients. Grafalon and Thymoglobulin seem to be equivalent to prevent acute rejection. CMV disease is more frequent in Thymoglobulin-treated patients. One year post-transplant immune profile profoundly differs according to the type of ATG. Copyright © 2017 Elsevier B.V. All rights reserved.

A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.

PubMed

Davis, Gary L; Nelson, David R; Terrault, Norah; Pruett, Timothy L; Schiano, Thomas D; Fletcher, Courtney V; Sapan, Christine V; Riser, Laura N; Li, Yufeng; Whitley, Richard J; Gnann, John W

2005-08-01

Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

Globulin Test

MedlinePlus

... of cancer Why do I need a globulin test? Your health care provider may order globulin tests as part your ... Globulin tests are blood tests. During a blood test, a health care professional will take a blood sample from a ...

What the world's religions teach, applied to vaccines and immune globulins.

PubMed

Grabenstein, John D

2013-04-12

For millennia, humans have sought and found purpose, solace, values, understanding, and fellowship in religious practices. Buddhist nuns performed variolation against smallpox over 1000 years ago. Since Jenner developed vaccination against smallpox in 1796, some people have objected to and declined vaccination, citing various religious reasons. This paper reviews the scriptural, canonical basis for such interpretations, as well as passages that support immunization. Populous faith traditions are considered, including Hinduism, Buddhism, Jainism, Judaism, Christianity, and Islam. Subjects of concern such as blood components, pharmaceutical excipients of porcine or bovine origin, rubella strain RA 27/3, and cell-culture media with remote fetal origins are evaluated against the religious concerns identified. The review identified more than 60 reports or evaluations of vaccine-preventable infectious-disease outbreaks that occurred within religious communities or that spread from them to broader communities. In multiple cases, ostensibly religious reasons to decline immunization actually reflected concerns about vaccine safety or personal beliefs among a social network of people organized around a faith community, rather than theologically based objections per se. Themes favoring vaccine acceptance included transformation of vaccine excipients from their starting material, extensive dilution of components of concern, the medicinal purpose of immunization (in contrast to diet), and lack of alternatives. Other important features included imperatives to preserve health and duty to community (e.g., parent to child, among neighbors). Concern that 'the body is a temple not to be defiled' is contrasted with other teaching and quality-control requirements in manufacturing vaccines and immune globulins. Health professionals who counsel hesitant patients or parents can ask about the basis for concern and how the individual applies religious understanding to decision-making about

Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy.

PubMed

Wittek, Riccardo

2006-05-01

In 1980 the World Health Organization declared that smallpox was eradicated from the world, and routine smallpox vaccination was discontinued. Nevertheless, samples of the smallpox virus (variola virus) were retained for research purposes, not least because of fears that terrorist groups or rogue states might also have kept samples in order to develop a bioweapon. Variola virus represents an effective bioweapon because it is associated with high morbidity and mortality and is highly contagious. Since September 11, 2001, countries around the world have begun to develop policies and preparedness programs to deal with a bioterror attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be associated with a number of serious adverse events, which can often be managed with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in patients for whom pre-exposure smallpox vaccine is contraindicated (such as those with eczema or pregnant women), although it is currently not licensed in these cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have been licensed by the FDA for the management of patients with progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body surface involvement or periocular implantation following inadvertent inoculation.

Analysis of Anthrax Immune Globulin Intravenous with Antimicrobial Treatment in Injection Drug Users, Scotland, 2009-2010.

PubMed

Cui, Xizhong; Nolen, Leisha D; Sun, Junfeng; Booth, Malcolm; Donaldson, Lindsay; Quinn, Conrad P; Boyer, Anne E; Hendricks, Katherine; Shadomy, Sean; Bothma, Pieter; Judd, Owen; McConnell, Paul; Bower, William A; Eichacker, Peter Q

2017-01-01

We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009-2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and we compared findings from 15 AIG-IV recipients with findings from 28 nonrecipients. Death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0-5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6-11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did nonrecipients. AIG-IV recipients were sicker than nonrecipients. This difference and the small number of higher risk patients confound assessment of AIG-IV effectiveness in this outbreak.

SHBG (Sex Hormone Binding Globulin)

MedlinePlus

... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

Updated Dosing Instructions for Immune Globulin (Human) GamaSTAN S/D for Hepatitis A Virus Prophylaxis.

PubMed

Nelson, Noele P

2017-09-15

GamaSTAN S/D (Grifols Therapeutics, Inc., Research Triangle Park, North Carolina) is a sterile, preservative-free solution of immune globulin (IG) for intramuscular administration and is used for prophylaxis against disease caused by infection with hepatitis A, measles, varicella, and rubella viruses (1). GamaSTAN S/D is the only IG product approved by the Food and Drug Administration for hepatitis A virus (HAV) prophylaxis. In July 2017, GamaSTAN S/D prescribing information was updated with changes to the dosing instructions for hepatitis A preexposure and postexposure prophylaxis indications. These changes were made because of concerns about decreased HAV immunoglobulin G antibody (anti-HAV IgG) potency, likely resulting from decreasing prevalence of previous HAV infection among plasma donors, leading to declining anti-HAV antibody levels in donor plasma (2). No changes in dosing instructions were made for measles, varicella, or rubella preexposure or postexposure prophylaxis.

Intravenous Immune Globulin in Children with Streptococcal Toxic Shock Syndrome

PubMed Central

Shah, Samir S.; Hall, Matthew; Srivastava, Raj; Subramony, Anupama; Levin, James E.

2009-01-01

Background Streptococcal toxic shock syndrome (TSS) is a rare and severe manifestation of group A streptococcal infection. The role of intravenous immune globulin (IVIG) for streptococcal TSS in children is controversial. Objective To describe the epidemiology of streptococcal TSS in children and to determine whether adjunctive therapy with IVIG is associated with improved outcomes. Methods A multicenter retrospective cohort study of children with streptococcal TSS from 2003-2007 was conducted. Propensity scores were used to determine each child's likelihood of receiving IVIG. Differences in the primary outcomes of death, hospital length of stay, and total hospital costs were compared after matching IVIG-recipients and non-recipients on propensity score. Results The median age was 8.2 years. IVIG was administered to 84 (44%) of 192. Overall mortality was 4.2% (95% confidence interval: 1.8% to 8.0%). Differences in mortality between IVIG recipients (n=3, 4.5%) and non-recipients (n=3, 4.5%) were not statistically significant (P=1.00). While patients receiving IVIG had higher total hospital and drug costs than non-recipients, differences in hospital costs were not significant once drug costs were removed (median difference between matched patients, $6,139; interquartile range: -$8,316 to $25,993; P=0.06). There were no differences in length of stay between matched IVIG recipients and non-recipients. Conclusion This multicenter study is the largest to describe the epidemiology and outcomes of children with streptococcal TSS and the first to explore the association between IVIG use and clinical outcomes. IVIG use was associated with increased costs of caring for children with streptococcal TSS but was not associated with improved outcomes. PMID:19788359

Should cell-free DNA testing be used to target antenatal rhesus immune globulin administration?

PubMed

Ma, Kimberly K; Rodriguez, Maria I; Cheng, Yvonne W; Norton, Mary E; Caughey, Aaron B

2016-01-01

To compare the rates of alloimmunization with the use of cell-free DNA (cfDNA) screening to target antenatal rhesus immune globulin (RhIG) prenatally, versus routine administration of RhIG in rhesus D (RhD)-negative pregnant women in a theoretic cohort using a decision-analytic model. A decision-analytic model compared cfDNA testing to routine antenatal RhIG administration. The primary outcome was maternal sensitization to RhD antigen. Sensitivity and specificity of cfDNA testing were assumed to be 99.8% and 95.3%, respectively. Univariate and bivariate sensitivity analyses, Monte Carlo simulation, and threshold analyses were performed. In a cohort of 10,000 RhD-negative women, 22.6 sensitizations would occur with utilization of cfDNA, while 20 sensitizations would occur with routine RhIG. Only when the sensitivity of the cfDNA test reached 100%, the rate of sensitization was equal for both cfDNA and RhIG. Otherwise, routine RhIG minimized the rate of sensitization, especially given RhIG is readily available in the United States. Adoption of cfDNA testing would result in a 13.0% increase in sensitization among RhD-negative women in a theoretical cohort taking into account the ethnic diversity of the United States' population.

Vitamin B6 status, immune response and inflammation markers in kidney transplant recipients treated with polyclonal anti-thymocyte globulin.

PubMed

Jankowska, M; Trzonkowski, P; Dębska-Ślizień, A; Marszałł, M; Rutkowski, B

2014-10-01

Vitamin B6 status has an impact on the body's inflammatory and immune responses. Immunosuppressive therapy may influence vitamin B6 metabolism in kidney transplant recipients. Treatment with polyclonal anti-thymocyte globulin (ATG) is associated with long-term changes in inflammatory and immune parameters. It is not known if ATG therapy also may have an impact on vitamin B6 status in kidney transplant recipients. We aimed to analyze the impact of therapy with ATG on vitamin B6 status, immune response, and the profile of inflammatory cytokines. This was a retrospective, observational study that included 44 kidney allograft recipients. Twenty patients received induction therapy with ATG (6 to 24 months before enrollment). Twenty-four patients constituted the control group, matched with respect to time since transplantation. The B6 vitamers, total lymphocyte count, CD3 percentage, interleukin (IL)-6, -7, and -10, transforming growth factor β, interferon γ, and chemokine ligand 21 were analyzed in a study group. All indicators of vitamin B6 status were lower in the ATG group than in the control group. There were also significant differences with respect to immune response (significantly lower total lymphocyte count and CD3 in the ATG group) and inflammatory status (significantly higher IL-6 and IL-10 in the ATG group). Vitamin B6 vitamers and derivatives were not related to lymphocyte count and cytokine levels or to estimated glomerular filtration rate and age of the study population. Vitamin B6 stores and active forms are lower in kidney transplant recipients treated with ATG. ATG therapy promotes CD3 and total lymphocyte depletion and increases indicators of inflammation. We found no associations between vitamers of B6, immune response cells, and inflammatory cytokines in study population.

Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin.

PubMed

Vora, Neil M; Orciari, Lillian A; Bertumen, J Bradford; Damon, Inger; Ellison, James A; Fowler, Vance G; Franka, Richard; Petersen, Brett W; Satheshkumar, P S; Schexnayder, Stephen M; Smith, Todd G; Wallace, Ryan M; Weinstein, Susan; Williams, Carl; Yager, Pamela; Niezgoda, Michael

2018-02-09

Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody…test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.

Postexposure prevention of progressive vaccinia in SCID mice treated with vaccinia immune globulin.

PubMed

Fisher, R W; Reed, J L; Snoy, P J; Mikolajczyk, M G; Bray, M; Scott, D E; Kennedy, M C

2011-01-01

A recently reported case of progressive vaccinia (PV) in an immunocompromised patient has refocused attention on this condition. Uniformly fatal prior to the licensure of vaccinia immune globulin (VIG) in 1978, PV was still fatal in about half of VIG-treated patients overall, with a greater mortality rate in infants and children. Additional therapies would be needed in the setting of a smallpox bioterror event, since mass vaccination following any variola virus release would inevitably result in exposure of immunocompromised people through vaccination or contact with vaccinees. Well-characterized animal models of disease can support the licensure of new products when human studies are not ethical or feasible, as in the case of PV. We chose vaccinia virus-scarified SCID mice to model PV. As in immunocompromised humans, vaccinia virus-scarified SCID animals develop enlarging primary lesions with minimal or no inflammation, eventual distal virus spread, and lethal outcomes if left untreated. Postexposure treatment with VIG slowed disease progression, caused local lesion regression, and resulted in the healthy survival of most of the mice for more than 120 days. Combination treatment with VIG and topical cidofovir also resulted in long-term disease-free survival of most of the animals, even when initiated 7 days postinfection. These results support the possibility that combination treatments may be effective in humans and support using this SCID model of PV to test new antibody therapies and combination therapies and to provide further insights into the pathogenesis and treatment of PV.

PROPERTIES OF VARIOUS ANTI-γ-GLOBULIN FACTORS IN HUMAN SERA

PubMed Central

Harboe, Morten; Rau, Barbara; Aho, Kimmo

1965-01-01

The serological and physicochemical properties of the following three forms of human anti-γ-globulin factors were compared: (a) rheumatoid factors; (b) Milgrom type anti-γ-globulin factors; and (c) factors directed against an antigen in human γG-globulin that is hidden in the intact molecule and revealed by enzymatic digestion at low pH. The property common to these factors is ability to interact with human γG-globulin; they are distinguishable because they react with different antigenic groups on this molecule. In all of five sera, the Milgrom type anti-γ-globulin factors were γM-globulins. They reacted with various human γG-globulin antibodies but failed to interact with γM-globulin type antibodies in agglutination and absorption experiments. When isolated from other anti-γ-globulin factors, they agglutinated red cells coated with intact anti-Rh antibodies, but failed to react with cells cells coated with pepsin-digested anti-Rh antibody. These observations indicate that the agglutinator reacts with the crystallizable, inert fragment of γG-globulin. Anti-γ-globulin activity directed against an antigen in human γG-globulin revealed by pepsin digestion was demonstrated in γG-, γA-, and γM-globulins. This anti-γ-globulin factor could be absorbed by antigen-antibody precipitates containing human antibody, which shows that the hidden antigen in human γG-globulin is revealed not only by enzymatic digestion at low pH, but also when γG-globulin is present as antibody in an antigen-antibody precipitate. Rheumatoid factors and Milgrom type anti-γ-globulin factors were also absorbed by antigen-antibody precipitates containing human antibody. The results indicate that the three distinct forms of antiγ-globulin factors may all be produced as a result of antigenic stimulation by autologous antigen-antibody complexes. PMID:14276773

Genetics Home Reference: inherited thyroxine-binding globulin deficiency

MedlinePlus

... Health Conditions Inherited thyroxine-binding globulin deficiency Inherited thyroxine-binding globulin deficiency Printable PDF Open All Close ... to view the expand/collapse boxes. Description Inherited thyroxine-binding globulin deficiency is a genetic condition that ...

Lack of association between Rh status, Rh immune globulin in pregnancy and autism.

PubMed

Miles, Judith H; Takahashi, T Nicole

2007-07-01

Though causes of autism are considered largely genetic, considerable concern remains that exposure to Rh immune globulin (RhIg), which until 2001 in the United States contained the preservative thimerosal, can cause autism. To determine whether mothers of children with autism are more likely to be Rh negative (Rh(-)) or to have received RhIg preserved with thimerosal, which is 49.6% ethyl mercury, we surveyed families of children with an autism spectrum disorder (ASD) ascertained through a University-based autism clinic considered free of ascertainment biases related to type of autism or severity. Between 2004 and 2006, 305 mothers of 321 children with an ASD agreed to participate in a telephone interview. Analysis of complete records including the blood group status and RhIg exposure of 214 families showed that Rh(-) status is no higher in mothers of children with autism than in the general population, exposure to antepartum RhIg, preserved with thimerosal is no higher for children with autism and pregnancies are no more likely to be Rh incompatible. This was also true for autism subgroups defined by behavioral phenotype, gender, IQ, regressive onset, head circumference, dysmorphology, birth status, essential, or complex phenotype. These findings support the consensus that exposure to ethylmercury in thimerosal is not the cause of the increased prevalence of autism. These data are important not only for parents in this country but also for the international health community where thimerosal continues to be used to preserve multi-dose vials which in turn makes vaccines affordable. (c) 2007 Wiley-Liss, Inc.

Comparative study of two human diploid rabies vaccines administered with antirabies globulin.

PubMed

Vodopija, I; Sureau, P; Smerdel, S; Lafon, M; Baklaic, Z; Ljubicic, M; Svjetlicic, M

1988-12-01

The association of human rabies immune globulin (HRIG) to the vaccine is recommended for postexposure rabies treatment in cases of severe exposure. In a previous study using an abbreviated postexposure vaccination schedule it was observed that passive immunization could partially inhibit the active immune response, with three cell-culture purified vaccines but not with the concentrated human diploid cell vaccine (HDCV). In order to see if this difference was related to the purification process, the present study was designed comparing two HDCV, one concentrated and the other concentrated and purified, both of them administered in association with HRIG. The neutralizing antibody response in the vaccines was found to be identical with both vaccines, ruling out the role of the purification and confirming the excellent immunogenicity of both human diploid cell vaccines and the absence of inhibition of the active immune response by the association of HRIG to HDCV.

Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study

PubMed Central

Sparks, Susan; Rakocevic, Goran; Joe, Galen; Manoli, Irini; Shrader, Joseph; Harris-Love, Michael; Sonies, Barbara; Ciccone, Carla; Dorward, Heidi; Krasnewich, Donna; Huizing, Marjan; Dalakas, Marinos C; Gahl, William A

2007-01-01

Background Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as α-dystroglycan and neural cell adhesion molecule (NCAM), has been reported in HIBM. Methods We treated 4 HIBM patients with intravenous immune globulin (IVIG), in order to provide sialic acid, because IgG contains 8 μmol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals. Results For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22%) directly after IVIG loading to 25.6 kg (+35%) at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44%) directly after IVIG loading to 6.0 kg (+46%) at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for α-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting. Conclusion The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM. PMID:17261181

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Globulin. (a) Proper name and definition. The proper name of this product shall be Anti-Human Globulin... in tissue cultures or in secondary hosts. [50 FR 5579, Feb. 11, 1985, as amended at 65 FR 77499, Dec...

Langerhans Cell Histiocytosis in an Adult with Involvement of the Calvarium, Cerebral Cortex and Brainstem: Discussion of Pathophysiology and Rationale for the Use of Intravenous Immune Globulin

PubMed Central

Dardis, Christopher; Aung, Thandar; Shapiro, William; Fortune, John; Coons, Stephen

2015-01-01

We report a case of Langerhans cell histiocytosis in a 64-year-old male who presented with symptoms and signs of brain involvement, including seizures and hypopituitarism. The diagnosis was confirmed with a biopsy of a lytic skull lesion. The disease affecting the bone showed no sign of progression following a short course of cladribine. Signs of temporal lobe involvement led to an additional biopsy, which showed signs of nonspecific neurodegeneration and which triggered status epilepticus. Lesions noted in the brainstem were typical for the paraneoplastic inflammation reported in this condition. These lesions improved after treatment with cladribine. They remained stable while on treatment with intravenous immune globulin. PMID:25873887

ACTIVITY OF DISSOCIATED AND REASSOCIATED 19S ANTI-γ-GLOBULINS

PubMed Central

Schrohenloher, Ralph E.; Kunkel, Henry G.; Tomasi, Thomas B.

1964-01-01

19S anti-γ-globulins were isolated in a high state of purity from the sera of two patients with rheumatoid arthritis. Following reduction with ethyl mercaptan and alkylation by iodoacetamide, fragments were produced which retained the capacity to combine with 7S γ-globulin. The fragments from one of the 19S anti-γ-globulins agglutinated red cells coated with incomplete anti-Rh antibodies. This activity was shown by density gradient ultracentrifugation to be associated with low molecular weight fractions. The agglutination of the coated red cells by the fragments was strongly inhibited by normal and myeloma 7S γ-globulins and showed a greater specificity than the parent 19S material. Analytical ultracentrifuge experiments demonstrated that the fragments from either of the 19S anti-γ-globulins formed complexes with 7S γ-globulin. Reassociation of the dissociated fragments through reformation of disulfide bonds resulted in the formation of fast sedimenting molecules having properties similar to those of the untreated 19S material in respect to precipitation with aggregated γ-globulin and agglutination of coated red cells. PMID:14238936

Role of intravenous immune globulin in streptococcal toxic shock syndrome and Clostridium difficile infection.

PubMed

Shah, Punit J; Vakil, Niyati; Kabakov, Anna

2015-06-15

The use of intravenous immune globulin (IVIG) in the management of streptococcal toxic shock syndrome (STSS) and Clostridium difficile infection (CDI) is reviewed. IVIG has a wide range of uses in clinical practice, including STSS and CDI. It is an attractive option for these two infections because both infections are toxin mediated, and IVIG may contain antibodies that neutralize these toxins. For STSS and CDI, IVIG is often considered for use in critically ill patients who are not responding to traditional therapies. Several encouraging case reports and retrospective chart reviews have been published, highlighting the potential benefit of IVIG in such patients. However, its definitive role remains unclear, mainly due to the lack of high-level evidence. Data supporting its use have been extrapolated from retrospective chart reviews and case reports in which profound heterogeneity in patient populations and treatment modalities exist. The use of IVIG must be weighed carefully because it is not a benign product. As with the use of IVIG for STSS, the role of IVIG for CDI is unclear. Nonetheless, IVIG may serve as a useful adjunct therapy for patients suffering from severe complicated CDI (shock, ileus, or megacolon) who do not respond to conventional treatment. Adverse reactions to IVIG are mild and transitory and occur during or immediately after drug infusion. Although randomized, controlled trials supporting the use of IVIG for STSS and CDI are lacking, IVIG may be considered a last-line adjunct therapy in those patients for whom the clinical benefit outweighs the potential adverse effects of therapy. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Apparent effect of immune serum globulin prophylaxis in the military on viral hepatitis incidence in the civilian population in Israel.

PubMed

Green, M S; Block, C

1989-06-01

Since 1969, extensive use of immune serum globulin in the Israel Defence Force for prophylaxis against hepatitis A virus (HAV) infection has produced a sharp decline in the incidence of the disease. However, it is not clear whether this policy has affected the susceptibility of Israeli adults to HAV infection. In this study, we examined the effect of the immunisation policy on the incidence of hepatitis A virus infection in the civilian population in the 15-44 year age group, which includes all those who have completed compulsory military service since vaccination was introduced. The incidence of viral hepatitis in the Jewish civilian population aged 15-44 increased by approximately 50% 3-4 years after the implementation of the immunisation policy. This rise was not seen in the non-Jewish population of the same age nor among Jews aged 45-64. These findings strongly suggest that the immunisation policy in the military prevents both clinical and sub-clinical disease, but has had the effect of producing more susceptible people at an older age in the civilian population.

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5400 Alpha-globulin immuno-logical test system. (a) Identification. An alpha-globulin immunological... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-globulin immuno-logical test system. 866...

Classification of Blood-Group Antibodies as β2M or γ Globulin

PubMed Central

Adinolfi, M.; Polley, Margaret J.; Hunter, Denise A.; Mollison, P. L.

1962-01-01

Thirty selected blood-group antibodies (excluding anti-A and anti-B) have been classified as β2M (19S γ) globulin, γ (7S γ) globulin or mixtures, using the following three methods: fractionation on a DEAE-cellulose column; indirect anti-globulin tests, using specific anti-β2M-globulin and anti-γ-globulin sera; and treatment with 2-mercapto-ethanol. With only minor exceptions, results obtained with the three methods were in agreement. Most blood-group antibodies within the Le, MNSs and P systems appear to be `naturally occurring' and these were found to be β2M globulin. Blood-group antibodies within the Rh, K and Jk systems, which had arisen after an antigenic stimulus, were usually γ globulin but were occasionally β2M globulin. Antibodies composed of β2M globulin usually behave as agglutinins but may behave as incomplete antibodies (e.g. some examples of anti-Jka); conversely, antibodies composed of γ globulin usually behave as incomplete antibodies but may behave as agglutinins (e.g. an example of anti-M). The ability to bind complement seems to be related more to the blood-group specificity of the particular antibody than to its molecular size. For example, anti-Jka, when composed either of γ or β2M globulin, seems invariably to bind complement, whereas potent anti-M or anti-Rh, whether composed of γ or β2M globulin, do not bind complement. PMID:14011076

21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5160 Beta-globulin immunolog-ical test system. (a) Identification. A beta-globulin immunological test system is a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-globulin immunolog-ical test system. 866.5160...

Serious infection risk and immune recovery after double-unit cord blood transplantation without antithymocyte globulin.

PubMed

Sauter, Craig; Abboud, Michelle; Jia, Xiaoyu; Heller, Glenn; Gonzales, Anne-Marie; Lubin, Marissa; Hawke, Rebecca; Perales, Miguel-Angel; van den Brink, Marcel R; Giralt, Sergio; Papanicolaou, Genovefa; Scaradavou, Andromachi; Small, Trudy N; Barker, Juliet N

2011-10-01

Factors contributing to infection risk after cord blood transplantation (CBT) include the use of anti-thymocyte globulin (ATG), prolonged neutropenia, and failure to transfer immunity. In the present study, we investigated the potential of double-unit CBT without ATG to reduce the risk of infection and evaluated the nature of serious infections in the first year after CBT using this approach. Seventy-two predominantly adult patients underwent CBT for hematologic malignancies; of these, 52 patients received myeloablative conditioning, and 20 received nonmyeloablative conditioning. The peak incidences of bacterial infections (32%), fungal infections (14%), and bacterial/fungal pneumonias (10%) occurred in the first 30 days posttransplantation. Three such infections contributed to early mortality. The peak incidence of viral infections was 31-60 days posttransplantation, affecting 30% of patients. Cytomegalovirus (CMV) was the most common viral infection. CMV infections occurring before day 120 (n = 23) had no relationship with graft-versus-host disease (GVHD), whereas CMV infections occurring after day 120 (n = 5), along with all cases of Epstein-Barr virus viremia (n = 5) and adenoviral enteritis (n = 2), occurred exclusively in the context of GVHD therapy or corticosteroid use for another indication. Viral infections had the highest lethality: 2 were a direct cause of death, and 3 contributed to death. Patients exhibited steady immune recovery, achieving a median CD3(+)4(+) T cell count >200 cells/μL by day 120 post-CBT, and no infection-related deaths occurred after day 120. Our results suggest that double-unit CBT without ATG is associated with prompt T cell recovery, and, unlike in CBT incorporating ATG, infection is rarely a primary cause of death. However, CBT without ATG is associated with a significant risk of GVHD, and serious infections remain a challenge, especially in the setting of GVHD. New strategies are needed to further reduce infectious

Acquired Immunological Tolerance to a Fraction of Bovine Gamma Globulin

PubMed Central

Dresser, D. W.

1961-01-01

A state of acquired immunological tolerance to bovine gamma globulin (BGG) has been observed in CBA mice injected with 10 mg. BGG within 12 hours of birth. Tolerance was demonstrated by a lack of immune elimination of 131I labelled BGG (BGG-131I) after prior challenge with Freund's adjuvant containing BGG. The degree of tolerance was found to diminish when the time between the tolerance injection and the challenge injection with adjuvant was increased. Mice were found to be tolerant 4 months after injection of 10 mg. BGG at birth but other similarly treated mice were found to be partially immune when challenged 6 months after the tolerance injection. This diminution of tolerance could be prevented by injections of antigen into adult mice whilst they were still tolerant. Precipitin and haemagglutination tests showed that antibody to BGG was present in mice shown to be tolerant to BGG by the antigen-elimination technique. The Ouchterlony double-diffusion technique showed that the mice were tolerant to one fraction of BGG but immune to at least one other fraction. The tolerated fraction of BGG was identified by means of starch-gel electrophoresis. ImagesFIG. 2 PMID:13724353

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

STUDIES ON STRUCTURAL UNITS OF THE γ-GLOBULINS

PubMed Central

Edelman, G. M.; Poulik, M. D.

1961-01-01

When human and rabbit 7S γ-globulins were reduced in strong urea solutions by a number of procedures, their molecular weights fell to approximately ⅓ of the original values. Partial separation of the reduction products was achieved using chromatography and starch gel electrophoresis in urea solutions. One of the components of reduced human 7S γ-globulin was isolated by chromatography, identified by starch gel electrophoresis, and subjected to amino acid analyses. The amino acid composition of this component differed from that of the starting material and also from that of the remaining components. A reduced pathological macroglobulin dissociated to components with an average molecular weight of 41,000. Several reduced human myeloma proteins, when subjected to starch gel electrophoresis, yielded individual patterns that nevertheless had features in common with those of reduced normal γ-globulins. Reduction of normal and abnormal γ-globulins was accompanied by the appearance of titratable sulfhydryl groups. Chemical treatments other than reduction were used to determine the type of bond holding the subunits together. It was tentatively concluded that they were linked by disulfide bonds. An hypothesis is presented to relate the structural features of the various γ-globulins in terms of the multiplicity of polypeptide chains in these molecules. PMID:13725659

Human antibodies to bovine alpha-globulin.

PubMed

Foucard, T; Bennich, H; Johansson, S G; Lundkvist, U

1975-01-01

Antibodies to bovine gamma-globulin (anti-BGG antibodies) were detectable by a radio-immunoassay in 70% of healthy blood donors but, generally, the titres were low. Significantly increased concentrations of anti-BGG antibodies were found in patients lacking IgA but not in patients with allergic disorders. The anti-BGG antibodies were shown to give rise to falsely high IgE values in the radio-immunosorbent test for IgE determination (RIST) when a sheep anti-IgE antiserum was used. Furthermore, falsely positive results can sometimes be caused by such antibodies in the determination of cow-dander- or cow's-milk-specific IgE by the radio-allergosorbent test (RAST). When a rabbit anti-IgE antiserum was used instead of the sheep anti-IgE, normal IgE levels and negative RAST results were obtained. The difference is explained by the higher degree of cross-reactivity between the anti-BGG antibodies and sheep alpha-globulin than between anti-BGG antibodies and rabbit alpha-globulin.

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

Genomic organization of the rat alpha 2u-globulin gene cluster.

PubMed

McFadyen, D A; Addison, W; Locke, J

1999-05-01

The alpha 2u-globulin are a group of similar proteins, belonging to the lipocalin superfamily of proteins, that are synthesized in a subset of secretory tissues in rats. The many alpha 2u-globulin isoforms are encoded by a multigene family that exhibits extensive homology. Despite a high degree of sequence identity, individual family members show diverse expression patterns involving complex hormonal, tissue-specific, and developmental regulation. Analysis suggests that there are approximately 20 alpha 2u-globulin genes in the rat genome. We have used fluorescence in situ hybridization (FISH) to show that the alpha 2u-globulin genes are clustered at a single site on rat Chromosome (Chr) 5 (5q22-24). Southern blots of rat genomic DNA separated by pulsed field gel electrophoresis indicated that the alpha 2u-globulin genes are contained on two NruI fragments with a total size of 880 kbp. Analysis of three P1 clones containing alpha 2u-globulin genes indicated that the alpha 2u-globulin genes are tandemly arranged in a head-to-tail fashion. The organization of the alpha 2u-globulin genes in the rat as a tandem array of single genes differs from the homologous major urinary protein genes in the mouse, which are organized as tandem arrays of divergently oriented gene pairs. The structure of these gene clusters may have consequences for the proposed function, as a pheromone transporter, for the protein products encoded by these genes.

Estimated protective effectiveness of intramuscular immune serum globulin post-exposure prophylaxis during a measles outbreak in British Columbia, Canada, 2014.

PubMed

Bigham, Mark; Murti, Michelle; Fung, Christina; Hemming, Felicity; Loadman, Susan; Stam, Robert; Van Buynder, Paul; Lem, Marcus

2017-05-09

Intramuscular Immune Serum Globulin (IM ISG) is recommended as post-measles exposure prophylaxis (PEP) when administered within 6days of initial exposure, with variable effectiveness in preventing measles disease. Effectiveness of IM ISG PEP in preventing clinical measles was assessed during a 2014 measles outbreak among a religious-affiliated community in British Columbia, Canada. Fifty-five self-reporting measles susceptible contacts were offered exclusively IM ISG PEP within an eligibility period best surmised to be within 6days of initial measles case exposure. Clinical outcome of IM ISG PEP recipients was determined by selective active surveillance and case self-reporting. IM ISG PEP failure was defined as onset of a measles-like rash 8-21days post-IM ISG PEP. Post-IM ISG PEP measles IgG antibody level was tested in 8 recipients. Factors associated with measles disease were analyzed. Seventeen of 55 IM ISG PEP recipients developed clinically consistent measles in the following 8-21days, corresponding to an estimated crude protective effectiveness of 69%. In school aged children 5-18years, among whom potential exposure intensity and immune status confounders were considered less likely, estimated IM ISG PEP protective effectiveness was 50%. Age <25years was significantly associated with breakthrough clinical measles in bivariate analysis (p=0.0217). Among 8 tested contacts of 17 considered IM ISG PEP failures, post-IM ISG PEP measles IgG antibody levels (mean 16.3days (range 16-17days) post-PEP) were all <150mIU/ml. The estimated crude IM ISG PEP protective effectiveness against measles disease within 8-21days post-ISG administration was 69%. Accuracy of this estimated protective effectiveness is vulnerable to assumptions and uncertainties in ascertaining exposure details and pre-exposure immune status. Increasing the Canadian recommended measles IM ISG PEP dose from 0.25 to 0.5ml/kg (up to 15ml maximum volume) may increase protective effectiveness. Copyright �

Physicochemical, functional and angiotensin converting enzyme inhibitory properties of amaranth (Amaranthus hypochondriacus) 7S globulin.

PubMed

Quiroga, Alejandra V; Aphalo, Paula; Ventureira, Jorge L; Martínez, E Nora; Añón, María C

2012-01-30

Amaranth 7S globulin is a minor globulin component and its impact on the properties of an amaranth protein ingredient depends on its proportion in the variety of amaranth being considered. Some physicochemical, functional and angiotesin I-converting enzyme (ACE) inhibitory properties of amaranth vicilin were studied in this work and compared with the 11S globulin. Fluorescence spectroscopy results indicated that 7S globulin tryptophans were more exposed to the solvent and, by calorimetry, the 7S globulin denaturation temperature (T(d) ) was found lower than the 11S globulin T(d) , suggesting a more flexible structure. The 7S globulin surface hydrophobicity was higher than that of the 11S globulin, which is in agreement with the better emulsifying properties of the 7S globulin. The solubility in neutral buffer of the 7S globulin (851 ± 25 g kg(-1) ) was also higher than that of the 11S globulin (195 ± 6 g kg(-1) ). Bioinformatic analyses showed the presence of ACE inhibitory peptides encrypted in 7S tryptic sequences and peptides released after in vitro gastrointestinal digestion showed a high ACE-inhibitory capacity (IC(50) = 0.17 g L(-1) ), similar to that of 11S globulin peptides. Compared with the 11S globulin, the 7S globulin presents similar ACE inhibitory activity and some functional advantages, better solubility and emulsifying activity, which suits some food requirements. The functional behavior has been related with the structural properties. Copyright © 2011 Society of Chemical Industry.

Assessment of acquired immune response to Rhipicephalus appendiculatus tick infestation in different goat breeds.

PubMed

Gopalraj, Jeyanthi B P; Clarke, Francoise C; Donkin, Edward F

2013-01-01

Changes in serum gamma globulin levels, numbers of replete female ticks and engorged tick mass were used as parameters to monitor the acquired immune response (antibody mediated immune response) elicited by Rhipicephalus appendiculatus adult tick infestations. Three consecutive Rhipicephalus appendiculatus adult tick infestations were applied to South African Indigenous goats (Nguni), Saanen goats and cross-bred goats (Saanen goats crossed with South African Indigenous goats [Nguni]) under laboratory conditions. During the three consecutive Rhipicephalus appendiculatus adult tick infestations the serum gamma globulin levels increased in all three breeds, whilst the mean replete female tick numbers and engorged tick mass decreased. Even though all three goat breeds exhibited an acquired immune response, the South African Indigenous goats (Nguni) response was significantly higher than that of the Saanen and cross-bred goats. However, the acquired immune response elicited by Saanen goats was significantly lower when compared with cross-bred goats.

Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

PubMed

Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

2017-09-01

Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

The effects of ALG on the murine immune response to sheep erythrocytes

PubMed Central

Anderson, Hilary R.; Dresser, D. W.; Iverson, G. M.; Lance, E. M.; Wortis, H. H.; Zebra, J.

1972-01-01

Antilymphocyte globulin (ALG), and to a lesser extent normal rabbit globulin (NRG), when given to mice prior to immunization with sheep-RBC suppress both the γM and γG2a responses. Globulin injected after the antigen suppresses the γG2a response, augments the γG1 response and has little effect on the γM response. These effects are also observed in mice partially paralysed to rabbit γ globulin. In another system—the response to hapten—protein conjugates precursors of antibody producing cells were found to be more resistant to ALS treatment in vivo than were helper cells. It is concluded that the suppressive effects of ALG treatment are largely due to the direct action of ALG on helper cells (T-cells). The mechanism of the adjuvant-like effect is unclear. PMID:4550853

[The macrophage disappearance reaction in guinea pigs sensitized with bovine gamma globulin or human scrum albumin (author's transl)].

PubMed

Schimke, R; Bernstein, B; Ambrosius, H

1977-01-01

The macrophage disappearance reaction (MDR) is a suitable test for detection of cell mediated immunity against bovine gamma globulin (BGG) and human serum albumin (HSA) in guinea pigs. The MDR is a technical simple, good manipulable, and quantifiable test. The optimal test conditions for the antigens BGC and HSA are the following: Peritoneal exudat cells (PEC) were stimulated with paraffin oil. On the 5th day after receiving oil the animals were injected with 80 microgram BGG or 30 microgram HSA i.p. 5 hours later the PEC were harvested and counted. With the MDR it is possible to detect differences with respect to degree of cell-mediated immunity. Supernatants of sensitized lymphocytes produces the MDR too.

Structural, Functional and Evolutionary Aspects of Seed Globulins.

PubMed

Kesari, Pooja; Neetu; Sharma, Anchal; Katiki, Madhusudhanarao; Kumar, Pramod; Gurjar, Bhola R; Tomar, Shailly; Sharma, Ashwani K; Kumar, Pravindra

2017-01-01

Globulins are a major class of seed storage proteins which were thought to be enzymatically inactive. These proteins belong to the most ancient cupin superfamily. They can be graded into 11S legumin type and 7S vicilin type based on their sedimentation coefficients. Members from both classes share structural homology are thought to have evolved from either one-domain germin predecessor by duplication or by horizontal gene transfer of two-domain gene from bacteria to eukaryotes. Globulins are known to define the nutritional quality of the seeds, however, they are also involved in sucrose binding, desiccation, defense against microbes, hormone binding and oxidative stress etc. Major drawback with globulins is their tendency to bind to IgE. Studying structural-functional behavior of such protein can help in modifying proteins for enhanced functionality in food processing industries. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Investigation of whether the acute hemolysis associated with Rho(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model

PubMed Central

Gaines, Ann Reed; Lee-Stroka, Hallie; Byrne, Karen; Scott, Dorothy E.; Uhl, Lynne; Lazarus, Ellen; Stroncek, David F.

2012-01-01

BACKGROUND Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rho(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis—the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV–associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV–associated acute hemolysis results from RBC antigen-antibody–mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. STUDY DESIGN AND METHODS Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. RESULTS Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. CONCLUSION Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV–associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. PMID:19220820

Meta-analysis of treatment with rabbit and horse antithymocyte globulin for aplastic anemia.

PubMed

Hayakawa, Jin; Kanda, Junya; Akahoshi, Yu; Harada, Naonori; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Yamazaki, Rie; Kako, Shinichi; Kanda, Yoshinobu

2017-05-01

Aplastic anemia patients who received rabbit antithymocyte globulin exhibited response and survival rates inferior to those who received horse antithymocyte globulin in several studies. Therefore, we conducted a meta-analysis to compare rabbit and horse antithymocyte globulin as immunosuppressive therapy for aplastic anemia. We searched online databases for studies that compared antithymocyte globulin regimens as first-line treatment for aplastic anemia, including both randomized and non-randomized controlled trials. The early mortality rate at 3 months and overall response rate at 6 months were evaluated. Thirteen studies were included in the analysis. The risk ratio (RR) of early mortality for rabbit vs. horse antithymocyte globulin was 1.33 [95% confidence interval (CI) 0.69-2.57; P = 0.39], with significant heterogeneity. A sensitivity analysis suggested higher early mortality rate in patients who received rabbit antithymocyte globulin. The overall response rate was significantly higher in patients who received horse antithymocyte globulin (RR 1.27; 95% CI 1.05-1.54; P = 0.015). In conclusion, in aplastic anemia patients treated with ATG, early mortality rate was not significantly different in patients receiving horse or rabbit ATG, although a sensitivity analysis showed higher early mortality in the rabbit ATG group. Horse ATG was associated with significantly higher response rate than rabbit ATG.

Polyclonal antithymocyte globulin and cardiovascular disease in kidney transplant recipients.

PubMed

Ducloux, Didier; Courivaud, Cécile; Bamoulid, Jamal; Crepin, Thomas; Chalopin, Jean-Marc; Tiberghien, Pierre; Saas, Philippe

2014-06-01

T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)-induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8(+) T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs. Copyright © 2014 by the American Society of Nephrology.

Polyclonal Antithymocyte Globulin and Cardiovascular Disease in Kidney Transplant Recipients

PubMed Central

Courivaud, Cécile; Bamoulid, Jamal; Crepin, Thomas; Chalopin, Jean-Marc; Tiberghien, Pierre; Saas, Philippe

2014-01-01

T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)–induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8+ T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs. PMID:24511120

Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia.

PubMed

Kekre, Natasha; Zhang, Ying; Zhang, Mei-Jie; Carreras, Jeanette; Ahmed, Parvez; Anderlini, Paolo; Atta, Elias Hallack; Ayas, Mouhab; Boelens, Jaap Jan; Bonfim, Carmem; Deeg, H Joachim; Kapoor, Neena; Lee, Jong-Wook; Nakamura, Ryotaro; Pulsipher, Michael A; Eapen, Mary; Antin, Joseph H

2017-07-01

For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using human leukocyte antigen (HLA)-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. There were no differences in hematopoietic recovery by type of antithymocyte globulin. Among recipients of HLA-matched sibling transplants, day 100 incidence of acute (17% versus 6%, P <0.001) and chronic (20% versus 9%, P <0.001) graft- versus -host disease were higher with horse compared to rabbit antithymocyte globulin. There were no differences in 3-year overall survival, 87% and 92%, P =0.76, respectively. Among recipients of unrelated donor transplants, acute graft- versus -host disease was also higher with horse compared to rabbit antithymocyte globulin (42% versus 23%, P <0.001) but not chronic graft- versus -host disease (38% versus 32%, P =0.35). Survival was lower with horse antithymocyte globulin after unrelated donor transplantation, 75% versus 83%, P =0.02. These data support the use of rabbit antithymocyte globulin for bone marrow transplant conditioning for severe aplastic anemia. Copyright© 2017 Ferrata Storti Foundation.

Posttransplant Immune Activation

PubMed Central

Bamoulid, Jamal; Crepin, Thomas; Rebibou, Jean-Michel; Courivaud, Cecile; Saas, Philippe

2017-01-01

Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8+ T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8+ T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence. PMID:29113470

A simple and rapid Hepatitis A Virus (HAV) titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations

PubMed Central

Konduru, Krishnamurthy; Virata-Theimer, Maria Luisa; Yu, Mei-ying W; Kaplan, Gerardo G

2008-01-01

Background Hepatitis A virus (HAV), the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers. Results We developed an antibiotic resistance titration assay (ARTA) based on the infection of human hepatoma cells with a wild type HAV construct containing a blasticidin (Bsd) resistance gene. Human hepatoma cells infected with the HAV-Bsd construct survived selection with 2 μg/ml of blasticidin whereas uninfected cells died within a few days. At 8 days postinfection, the color of the pH indicator phenol red in cell culture media correlated with the presence of HAV-Bsd-infected blasticidin-resistant cells: an orange-to-yellow color indicated the presence of growing cells whereas a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were determined by an endpoint dilution assay based on the color of the cell culture medium scoring orange-to-yellow wells as positive and pink-to-purple wells as negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV neutralization potency of two commercially available human immune globulin (IG) preparations and a WHO International Standard for anti-HAV. The three IG preparations contained comparable levels of anti-HAV antibodies that neutralized approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in the absence of blasticidin by an endpoint dilution ELISA at 2 weeks postinfection. Conclusion The ARTA is a simple and rapid method to determine HAV titers without using HAV-specific probes. We determined the HAV neutralization potency of human IG preparations in 8 days by ARTA compared to the 14 days required by the endpoint dilution ELISA

Anti-thymocyte globulins in kidney transplantation: focus on current indications and long-term immunological side effects.

PubMed

Bamoulid, Jamal; Staeck, Oliver; Crépin, Thomas; Halleck, Fabian; Saas, Philippe; Brakemeier, Susanne; Ducloux, Didier; Budde, Klemens

2017-10-01

Antithymocyte globulins (ATGs) are part of the immunosuppression arsenal currently used by clinicians to prevent or treat acute rejection in solid organ transplantation. ATG is a mixture of non-specific anti-lymphocyte immunoglobulins targeting not only T cell subsets but also several other immune and non-immune cells, rendering its precise immunoglobulin composition difficult to appreciate or to compare from one preparation to another. Furthermore, several mechanisms of action have been described. Taken together, this probably explains the efficacy and the side effects associated with this drug. Recent data suggest a long-term negative impact on allograft and patient outcomes, pointing out the need to better characterize the potential toxicity and the benefit-risk balance associated to this immunosuppressive therapy within large clinical trials. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Enhanced Efficacy of Cidofovir Combined with Vaccinia Immune Globulin in Treating Progressive Cutaneous Vaccinia Virus Infections in Immunosuppressed Hairless Mice

PubMed Central

Dagley, Ashley; Downs, Brittney; Hagloch, Joseph; Tarbet, E. Bart

2014-01-01

The treatment of progressive vaccinia in individuals has involved antiviral drugs, such as cidofovir (CDV), brincidofovir, and/or tecovirimat, combined with vaccinia immune globulin (VIG). VIG is costly, and its supply is limited, so sparing the use of VIG during treatment is an important objective. VIG sparing was modeled in immunosuppressed mice by maximizing the treatment benefits of CDV combined with VIG to determine the effective treatments that delayed the time to death, reduced cutaneous lesion severity, and/or decreased tissue viral titers. SKH-1 hairless mice immunosuppressed with cyclophosphamide and hairless SCID mice (SHO strain) were infected cutaneously with vaccinia virus. Monotherapy, dual combinations (CDV plus VIG), or triple therapy (topical CDV, parenteral CDV, and VIG) were initiated 2 days postinfection and were given every 3 to 4 days through day 11. The efficacy assessment included survival rate, cutaneous lesion severity, and viral titers. Delays in the time to death and the reduction in lesion severity occurred in the following order of efficacy: triple therapy had greater efficacy than double combinations (CDV plus VIG or topical plus parenteral CDV), which had greater efficacy than VIG alone. Parenteral administration of CDV or VIG was necessary to suppress virus titers in internal organs (liver, lung, and spleen). The skin viral titers were significantly reduced by triple therapy only. The greatest efficacy was achieved by triple therapy. In humans, this regimen should translate to a faster cure rate, thus sparing the amount of VIG used for treatment. PMID:25385098

21 CFR 862.1330 - Globulin test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862... other disorders of blood globulins. (b) Classification. Class I (general controls). The device is exempt...

Multihormonal induction of hepatic α2u-globulin mRNA as measured by hybridization to complementary DNA

PubMed Central

Kurtz, David T.; Feigelson, Philip

1977-01-01

A procedure is presented for the preparation of a 3H-labeled complementary DNA (cDNA) specific for the mRNA coding for α2u-globulin, a male rat liver protein under multihormonal control that represents approximately 1% of hepatic protein synthesis. Rat liver polysomes are incubated with monospecific rabbit antiserum to α2u-globulin, which binds to the nascent α2u-globulin chains on the polysomes. These antibody-polysome complexes are then adsorbed to goat antiserum to rabbit IgG that is covalently linked to p-aminobenzylcellulose. mRNA preparations are thus obtained that contain 30-40% α2u-globulin mRNA. A labeled cDNA is made to this α2u-globulin-enriched mRNA preparation by using RNA-dependent DNA polymerase (reverse transcriptase). To remove the non-α2u-globulin sequences, this cDNA preparation is hybridized to an RNA concentration × incubation time (R0t) of 1000 mol of ribonucleotide per liter × sec with female rat liver mRNA, which, though it shares the vast majority of mRNA sequences with male liver, contains no α2u-globulin mRNA sequences. The cDNA remaining single-stranded is isolated by hydroxylapatite chromatography and is shown to be specific for α2u-globulin mRNA by several criteria. Good correlation was found in all endocrine states studied between the hepatic level of α2u-globulin, the level of functional α2u-globulin mRNA as assayed in a wheat germ cell-free translational system, and the level of α2u-globulin mRNA sequences as measured by hybridization to the α2u-globulin cDNA. Thus, the hormonal control of hepatic α2u-globulin synthesis by sex steroids and thyroid hormone occurs through modulation of the cellular level of α2u-globulin mRNA sequences, presumably by hormonal control of transcriptive synthesis. PMID:73184

Serum IgG, IgM and slow alpha-globulin levels in carrageenan-treated rats.

PubMed Central

Fowler, E. F.; Thomson, A. W.

1979-01-01

Serum levels of IgM, IgG, slow alpha 1- and slow alpha 2-globulins were measured either by quantitative radial immunodiffusion (IgG) or immunoelectrophoresis (IgM and slow alpha-globulins) during the 3-week period after i.p. injection of 50 mg potassium carrageenan. There was a significant elevation in levels of IgM and slow alpha 1-globulin, maximal on Day 4 and returning to normal by Day 14. Slow alpha 2-globulin was detectable within 24 h, reached a peak at Day 2, and was no longer measurable in most rats by Day 14. Levels of IgG however, were unaffected by carrageenan injection. PMID:92333

A simplified immune suppression scheme leads to persistent micro-dystrophin expression in Duchenne muscular dystrophy dogs.

PubMed

Shin, Jin-Hong; Yue, Yongping; Srivastava, Arun; Smith, Bruce; Lai, Yi; Duan, Dongsheng

2012-02-01

Highly abbreviated micro-dystrophin genes have been intensively studied for Duchenne muscular dystrophy (DMD) gene therapy. Following adeno-associated virus (AAV) gene transfer, robust microgene expression is achieved in murine DMD models in the absence of immune suppression. Interestingly, a recent study suggests that AAV gene transfer in dystrophic dogs may require up to 18 weeks' immune suppression using a combination of three different immune-suppressive drugs (cyclosporine, mycophenolate mofetil, and anti-dog thymocyte globulin). Continued immune suppression is not only costly but also may cause untoward reactions. Further, some of the drugs (such as anti-dog thymocyte globulin) are not readily available. To overcome these limitations, we developed a novel 5-week immune suppression scheme using only cyclosporine and mycophenolate mofetil. AAV vectors (either AV.RSV.AP that expresses the heat-resistant human alkaline phosphatase gene, or AV.CMV.μDys that expresses the canine R16-17/H3/ΔC microgene) at 2.85×10(12) vg particles were injected into adult dystrophic dog limb muscles under the new immune suppression protocol. Sustained transduction was observed for nearly half year (the end of the study). The simplified immune suppression strategy described here may facilitate preclinical studies in the dog model.

Total Protein and Albumin/Globulin Ratio Test

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

Humoral and Cellular Immune Response in Canine Hypothyroidism.

PubMed

Miller, J; Popiel, J; Chełmońska-Soyta, A

2015-07-01

Hypothyroidism is one of the most common endocrine diseases in dogs and is generally considered to be autoimmune in nature. In human hypothyroidism, the thyroid gland is destroyed by both cellular (i.e. autoreactive helper and cytotoxic T lymphocytes) and humoral (i.e. autoantibodies specific for thyroglobulin, thyroxine and triiodothyronine) effector mechanisms. Other suggested factors include impaired peripheral immune suppression (i.e. the malfunction of regulatory T cells) or an additional pro-inflammatory effect of T helper 17 lymphocytes. The aim of this study was to evaluate immunological changes in canine hypothyroidism. Twenty-eight clinically healthy dogs, 25 hypothyroid dogs without thyroglobulin antibodies and eight hypothyroid dogs with these autoantibodies were enrolled into the study. There were alterations in serum proteins in hypothyroid dogs compared with healthy controls (i.e. raised concentrations of α-globulins, β2- and γ-globulins) as well as higher concentration of acute phase proteins and circulating immune complexes. Hypothyroid animals had a lower CD4:CD8 ratio in peripheral blood compared with control dogs and diseased dogs also had higher expression of interferon γ (gene and protein expression) and CD28 (gene expression). Similar findings were found in both groups of hypothyroid dogs. Canine hypothyroidism is therefore characterized by systemic inflammation with dominance of a cellular immune response. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of anticonvulsants on plasma testosterone and sex hormone binding globulin levels.

PubMed Central

Barragry, J M; Makin, H L; Trafford, D J; Scott, D F

1978-01-01

Plasma sex hormone binding globulin (SHBG) and testosterone levels were measured in 29 patients with epilepsy (16 men and 13 women), most of them on chronic therapy with anticonvulsant drugs. Sex hormone binding globulin concentrations were increased in both sexes and testosterone levels in male patients. It is postulated that anticonvulsants may induce hepatic synthesis of SHBG. PMID:569688

Local application of antirabies gamma-globulin in dried form for the prevention of rabies

PubMed Central

Soloviev, V. D.; Kobrinski, G. D.

1962-01-01

The authors report on guinea-pig experiments conducted to determine the effect of dried antirabies gamma-globulin in the local treatment of wounds infected with street rabies. The results showed that local application of dried gamma-globulin within 30 minutes of the time of infection of the wound protected the majority of animals and resulted in a considerably longer incubation period in the remainder than in the controls. When the preparation was applied later than 30 minutes after infection, the therapeutic effect was slight or absent. Optimum protection in these experiments was obtained through rapid application of gamma-globulin, followed by vaccination every other day for six days. Dried antirabies gamma-globulin exerts a specific, local action on the rabies virus and is entirely painless and non-destructive to body tissues. PMID:13915039

Follicle stimulating hormone, its novel association with sex hormone binding globulin in men and postmenopausal women.

PubMed

Wang, Ningjian; Zhang, Kun; Han, Bing; Li, Qin; Chen, Yi; Zhu, Chunfang; Chen, Yingchao; Xia, Fangzhen; Zhai, Hualing; Jiang, Boren; Shen, Zhoujun; Lu, Yingli

2017-06-01

Follicle stimulating hormone plays direct roles in a variety of nongonadal tissues and sex hormone binding globulin is becoming the convergence of the crosstalk among metabolic diseases. However, no studies have explored the association between follicle stimulating hormone and sex hormone binding globulin. We aimed to study this association among men and women. SPECT-China is a population-based study conducted since 2014. This study included 4206 men and 2842 postmenopausal women. Collected serum was assayed for gonadotropins, sex hormone binding globulin, sex hormones etc. Regression analyses were performed to assess the relationship between sex hormone binding globulin and follicle stimulating hormone and other variables including metabolic factors, thyroid function and sex hormones. Treatment with follicle stimulating hormone at different concentrations of 0, 5, 50 and 100 IU/L for 24 h was performed in HepG2 cells. In Spearman correlation, sex hormone binding globulin was significantly correlated with FSH, triglycerides, thyroxins, body mass index and blood pressure in men and postmenopausal women (all P < 0.05). In regression analyses, follicle stimulating hormone was a significant predictor of sex hormone binding globulin in men and postmenopausal women (P < 0.05), independent of above variables. Follicle stimulating hormone induced sex hormone binding globulin expression in a dose-dependent fashion in HepG2 cells. Serum follicle stimulating hormone levels were positively associated with circulating sex hormone binding globulin levels in men and postmenopausal women. This association is independent of age, insulin resistance, hepatic function, lipid profile, thyroid function, adiposity, blood pressure, and endogenous sex hormones.

Effects of medicinal herbs "Plantago asiatica", "Houttuynia cordata" and "Mentha haplocalyx" on non-specific immune responses of cobia (Rachycentron canadum).

PubMed

Wu, Yu-Sheng; Chen, Yin-Yu; Ueng, Pien-Sheng; Nan, Fan-Hua

2016-11-01

This study investigated the effects of orally administered Plantago asiatica, Houttuynia cordata, and Mentha haplocalyx on the growth and nonspecific immune responses of cobia (Rachycentron canadum). The nonspecific immune parameters assessed were weight gain, feed conversion ratio, superoxide anion (O 2 - ) production, superoxide dismutase (SOD) activity, phagocytic rate, phagocytic index, lysozyme activity, serum albumin and globulin, and albumin:globulin (A/G) ratio. The growth experiment indicated that 6-week dietary treatments did not significantly affect on the growth of cobia. Nonspecific immune responses showed that O 2 - production, SOD and lysozyme activity, and phagocytosis were significantly increased after the oral administration of P. asiatica and H. cordata, and the serum albumin:globulin ratio (A/G) gradually decreased. In this study, treatment of the Mentha haplocalyx on the cobia didn't present with the inducing of the phagocytosis ability compared with the treatment of P. asiatica and H. cordata. We suggest that oral administration of the 10 g/kg or 20 g/kg of the P. asiatica and H. cordata is exactly inducing the phagocytosis, ROS production, lysozyme activity and SOD production in the cobia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical and economic analysis of delayed administration of antithymocyte globulin for induction therapy in kidney transplantation.

PubMed

McGillicuddy, John W; Taber, David J; Pilch, Nicole A; Kohout, Ryan K; Bratton, Charles F; Chavin, Kenneth D; Baliga, Prabhakar K

2013-03-01

The increasing number of marginal deceased kidney donors and an aging recipient population, prolonged hospitalization, and increased costs have destabilized the economic viability of kidney transplants. To determine if a delay in the administration of the day-of-discharge dose of rabbit antithymocyte globulin would result in equivalent clinical outcomes with cost savings. Single-center, prospective, observational before-and-after study of adult kidney transplant recipients who received induction with rabbit antithymocyte globulin.Intervention-Patients who received a transplant between June 2006 and February 2009 and received rabbit antithymocyte globulin served as the control group. Patients who received a transplant between March 2009 and August 2010 and received rabbit antithymocyte globulin had the day-of-discharge dose delayed to the following day and administered in the clinic. A total of 231 patients (146 in the control group, 85 in the study group) were included. Baseline demographic and clinical characteristics were similar in the 2 groups. Patients who had delayed administration of rabbit antithymocyte globulin had shorter stays (3.9 vs 3.1 days, P< .001) and reduced inpatient costs for rabbit antithymocyte globulin (mean $860/patient); these changes were achieved without affecting acute rejection rates (5% vs 5%, P> .99) or readmission rates. In conclusion, delayed inpatient administration of rabbit antithymocyte globulin provided identical clinical outcomes while helping to reduce inpatient costs and increase timely discharges.

Proteomic analysis of albumin and globulin fractions of pea (Pisum sativum L.) seeds.

PubMed

Dziuba, Jerzy; Szerszunowicz, Iwona; Nałęcz, Dorota; Dziuba, Marta

2014-01-01

Proteomic analysis is emerging as a highly useful tool in food research, including studies of food allergies. Two-dimensional gel electrophoresis involving isoelectric focusing and sodium dodecyl sulfate polyacrylamide gel electrophoresis is the most effective method of separating hundreds or even thousands of proteins. In this study, albumin and globulin tractions of pea seeds cv. Ramrod were subjected to proteomic analysis. Selected potentially alergenic proteins were identified based on their molecular weights and isoelectric points. Pea seeds (Pisum sativum L.) cv. Ramrod harvested over a period of two years (Plant Breeding Station in Piaski-Szelejewo) were used in the experiment. The isolated albumins, globulins and legumin and vicilin fractions of globulins were separated by two-dimensional gel electrophoresis. Proteomic images were analysed in the ImageMaster 2D Platinum program with the use of algorithms from the Melanie application. The relative content, isoelectric points and molecular weights were computed for all identified proteins. Electrophoregrams were analysed by matching spot positions from three independent replications. The proteomes of albumins, globulins and legumin and vicilin fractions of globulins produced up to several hundred spots (proteins). Spots most characteristic of a given fraction were identified by computer analysis and spot matching. The albumin proteome accumulated spots of relatively high intensity over a broad range of pi values of ~4.2-8.1 in 3 molecular weight (MW) ranges: I - high molecular-weight albumins with MW of ~50-110 kDa, II - average molecular-weight albumins with MW of ~20-35 kDa, and III - low molecular-weight albumins with MW of ~13-17 kDa. 2D gel electrophoregrams revealed the presence of 81 characteristic spots, including 24 characteristic of legumin and 14 - of vicilin. Two-dimensional gel electrophoresis proved to be a useful tool for identifying pea proteins. Patterns of spots with similar isoelectric

Association of Central Obesity with Sex Hormonebinding Globulin: A Cross-sectional Study of 1166 Chinese Men.

PubMed

Liu, Fangwei; Shen, Xubo; Wang, Ruifeng; Yu, Na; Shi, Yongjun; Xiong, Shimin; Xiong, Chengliang; Zhou, Yuanzhong

2018-01-01

Background Both sex hormone-binding globulin and central obesity have been found to be associated with metabolic and cardiovascular diseases. However, the direct relation between sex hormone-binding globulin and central obesity has not been demonstrated. Methodology We performed a cross-sectional study of 1166 male participants from Zunyi, Guizhou, western China, in 2013. Each participant completed a questionnaire and had a brief clinical exam with a fasting blood sample taken. All blood samples underwent standard laboratory testing for sex hormone-binding globulin. Level of serum sex hormone-binding globulin was compared by demographic characteristics, and multiple linear regression was used to evaluate the independent association of variables and sex hormone-binding globulin level. Results The mean serum level of sex hormone-binding globulin was increased in old-aged men (older than 40 years; mean 44.68±20.58 nmol/L), low diastolic blood pressure (<90mmHg; 43.76±20.50 nmol/L), waist-to-height ratio <0.5 (48.73±20.59 nmol/L), no education (52.36±22.91 nmol/L), farm occupation (43.58±20.60nmol/L), non-alcohol or former user (44.78±20.94 nmol/L) and long-term medication history (44.79±21.50 nmol/L). Factors independently associated with sex hormone binding globulin level on multiple regression were waist-to-height ratio (β=- 11.84 [95% confidence interval -13.96,-9.72]), age(β=12.40 [9.63,15.17]) and diastolic blood pressure (β=-5.07 [-7.44,-2.71]). Conclusions Central obesity has an independent inverse relation with serum level of sex hormone binding globulin among western Chinese men.

Biosynthesis and Intracellular Transport of 11S Globulin in Developing Pumpkin Cotyledons 1

PubMed Central

Hara-Nishimura, Ikuko; Nishimura, Mikio; Akazawa, Takashi

1985-01-01

In vitro studies to explore the biosynthesis of 11S globulin developing cotyledons of pumpkin (Cucurbita sp.) demonstrated that 11S globulin is synthesized on membrane-bound polysomes. Mr of the translation products (preproglobulin) synthesized by the poly(A)+-RNA isolated from developing cotyledons were determined to be 64,000 and 59,000, which are larger than those of the mature globulin subunit (62,000 and 57,000). Preproglobulin is then cotranslationally processed by cleavage of the signal peptide to produce proglobulin. In vivo pulse-chase experiments showed the sequential transformation of the single-chain proglobulin to mature globulin subunit (disulfide-linked doublet polypeptides) indicating posttranslational modification of the proglobulin. Subcellular fractionation of the pulse-chased intact cotyledons showed that the [35S]methionine label is detectable in proglobulin in rough endoplasmic reticulum shortly after the pulse label. With time, the labeled proteins move into other cellular fractions: proglobulin in the density = 1.24 grams per cubic centimeter fractions after 30 minutes and mature globulin subunit associated with protein bodies after 1 to 2 hours. The distribution of proglobulin in sucrose density gradients did not correspond with those of catalase (microbody marker) or fumarase (mitochondria marker). An accumulation of proglobulin occurred in the density = 1.24 grams per cubic centimeter fractions, whereas the mature globulin was scarcely detectable in this fraction. In contrast, proglobulin was not detected by immunochemical blotting analysis in the protein bodies prepared under the mild conditions from cotyledon protoplasts. The results suggest that the d = 1.24 grams per cubic centimeter fractions are engaged in the translocation of proglobulin into the protein bodies. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:16664128

21 CFR 862.1330 - Globulin test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Globulin test system. 862.1330 Section 862.1330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

21 CFR 862.1330 - Globulin test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Globulin test system. 862.1330 Section 862.1330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

Sex hormone-binding globulin and corticosteroid-binding globulin mRNA levels in infertile women with luteal phase deficiency.

PubMed

Misao, R; Nakanishi, Y; Fujimoto, J; Tamaya, T

1995-09-01

This study was designed to investigate the biological significance in intracellular expression of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) mRNA in uterine endometrium with luteal phase deficiency (designated as out-of-phase endometrium or low serum progesterone level). The levels of such mRNAs were measured by the quantitative reverse transcription-polymerase chain reaction. Under the normal serum 17 beta-estradiol and progesterone levels in the mid-luteal phase, the levels of SHBG and CBG mRNAs in the out-of-phase endometria were not significantly different from those in the normal endometria. On the other hand, SHBG and CBG mRNA levels in the endometria of low serum midluteal progesterone level were significantly (p < 0.05) reduced and raised, respectively, compared with normal levels. These findings suggest that the synthesis of endometrial steroid-binding proteins in the out-of-phase endometrium is conserved, as that in the in-phase endometrium, whereas the decreased progesterone level might up-regulate CBG expression with down-regulation of SHBG expression.

Antibodies to the A27 protein of vaccinia virus neutralize and protect against infection but represent a minor component of Dryvax vaccine--induced immunity.

PubMed

He, Yong; Manischewitz, Jody; Meseda, Clement A; Merchlinsky, Michael; Vassell, Russell A; Sirota, Lev; Berkower, Ira; Golding, Hana; Weiss, Carol D

2007-10-01

The smallpox vaccine Dryvax, which consists of replication-competent vaccinia virus, elicits antibodies that play a major role in protection. Several vaccinia proteins generate neutralizing antibodies, but their importance for protection is unknown. We investigated the potency of antibodies to the A27 protein of the mature virion in neutralization and protection experiments and the contributions of A27 antibodies to Dryvax-induced immunity. Using a recombinant A27 protein (rA27), we confirmed that A27 contains neutralizing determinants and that vaccinia immune globulin (VIG) derived from Dryvax recipients contains reactivity to A27. However, VIG neutralization was not significantly reduced when A27 antibodies were removed, and antibodies elicited by an rA27 enhanced the protection conferred by VIG in passive transfer experiments. These findings demonstrate that A27 antibodies do not represent the major fraction of neutralizing activity in VIG and suggest that immunity may be augmented by vaccines and immune globulins that include strong antibody responses to A27.

Biochemistry of Fern Spore Germination: Globulin Storage Proteins in Matteuccia struthiopteris L. 1

PubMed Central

Templeman, Thomas S.; DeMaggio, Augustus E.; Stetler, David A.

1987-01-01

Two globulin storage proteins have been identified in spores of the ostrich fern, Matteuccia struthiopteris (L.) Todaro. The two proteins comprise a significant amount of the total spore protein, are predominantly salt-soluble, and can be extracted by other solvents to a limited extent. The large 11.3 Svedberg unit (S) globulin is composed of five polypeptides with molecular weights of 21,000, 22,000, 24,000, 28,000 and 30,000. Each polypeptide has several isoelectric point (pI) variants between pH 5 and 7. The small 2.2S storage protein has a pI > 10.5 and is composed of at least two major polypeptides of 6,000 and 14,000 Mr. The amino acid composition of both storage proteins reveals that the 11.3S protein is particularly rich in aspartic and glutamic acid, while the 2.2S protein has few acidic amino acids. During imbibition and germination the globulin fraction declines rapidly, with a corresponding degradation of individual polypeptides of each protein. Polyclonal antibodies against each of the two proteins were produced and used for immunolocalization to determine the site of storage protein deposition within the quiescent spore. The proteins were sequestered in protein bodies of 2 to 10 micrometers, that are morphologically similar to those found in the seeds of flowering plants. The results suggest that spore globulins are biochemically similar to seed globulins, especially those found in some cruciferous seeds. Images Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:16665699

Studies on Red Cell Aplasia. V. PRESENCE OF ERYTHROBLAST CYTOTOXICITY IN γG-GLOBULIN FRACTION OF PLASMA

PubMed Central

Krantz, Sanford B.; Moore, W. H.; Zaentz, S. Donald

1973-01-01

The marrow cells of a patient with pure red cell aplasia markedly increased their rate of heme synthesis when they were freed from the host environment and were incubated in vitro. When the red cell aplasia was treated with cyclophosphamide and prednisone, marrow cell incorporation of 59Fe into heme in vitro increased several weeks before a reticulocytosis was apparent, and was the earliest effect noted. The plasma γG-globulins of this patient inhibited heme synthesis by normal marrow cells or the patient's own marrow cells obtained after remission of the disease. Since the inhibition of heme synthesis could be the result of damage to erythroblasts, the patient's posttreatment marrow cells or normal marrow cells were labeled with 59Fe and were then incubated with the patient's pretreatment, treatment, and posttreatment γG-globulins as well as normal γG-globulins. At the end of this incubation the supernatant and cells were separated and counted. Heme was extracted and also was counted. Treatment of the cells with the patient's pretreatment γG-globulins resulted in a release of 40% of the radioactive heme from the cells. This represented the loss of radioactive hemoglobin and was an index of erythroblast cytotoxicity. A progressive disappearance of the cytotoxic factor in the γG-globulins occurred in the 3 wk period preceding the onset of reticulocytes in the patient's blood. Posttreatment and normal γG-globulins did not produce this effect and increased injury of red cells and lymphocytes was not produced by the patient's pretreatment γG-globulins. These studies demonstrate a method for measuring erythroblast cytoxicity and show that red cell aplasia is associated with γG-globulins that specifically damage erythroblasts. Whether interference with new erythroblast development also occurs and contributes to the inhibition of heme synthesis has not yet been ascertained. Images PMID:4119161

Ultrastructural studies of human and rabbit alpha-M-globulins.

PubMed

Bloth, B; Chesebro, B; Svehag, S E

1968-04-01

Electron micrographs of isolated human alpha(2)M-molecules, obtained by the negative contrast technique, revealed morphologically homogenous structures resembling a graceful monogram of the two letters H and I. The modal values for the length and width of the alpha(2)M particles were 170 A and 100 A, respectively. Purified rabbit alphamacroglobulins contained about 80% alpha(1)M- and 20% alpha(2)M-globulins. The isolated rabbit alpha(1)M- and alpha(2)M-molecules were morphologically indistinguishable from one another and from human alpha(2)M-molecules. Preliminary immunoprecipitation studies demonstrated that the two rabbit alphaM-globulins were antigenically different. Sedimentation constant determinations gave s(20, w) values of 18.8 and 18.2 for rabbit alpha(1)M and alpha(2)M, respectively.

Identification of three wheat globulin genes by screening a Triticum aestivum BAC genomic library with cDNA from a diabetes-associated globulin

PubMed Central

Loit, Evelin; Melnyk, Charles W; MacFarlane, Amanda J; Scott, Fraser W; Altosaar, Illimar

2009-01-01

Background Exposure to dietary wheat proteins in genetically susceptible individuals has been associated with increased risk for the development of Type 1 diabetes (T1D). Recently, a wheat protein encoded by cDNA WP5212 has been shown to be antigenic in mice, rats and humans with autoimmune T1D. To investigate the genomic origin of the identified wheat protein cDNA, a hexaploid wheat genomic library from Glenlea cultivar was screened. Results Three unique wheat globulin genes, Glo-3A, Glo3-B and Glo-3C, were identified. We describe the genomic structure of these genes and their expression pattern in wheat seeds. The Glo-3A gene shared 99% identity with the cDNA of WP5212 at the nucleotide and deduced amino acid level, indicating that we have identified the gene(s) encoding wheat protein WP5212. Southern analysis revealed the presence of multiple copies of Glo-3-like sequences in all wheat samples, including hexaploid, tetraploid and diploid species wheat seed. Aleurone and embryo tissue specificity of WP5212 gene expression, suggested by promoter region analysis, which demonstrated an absence of endosperm specific cis elements, was confirmed by immunofluorescence microscopy using anti-WP5212 antibodies. Conclusion Taken together, the results indicate that a diverse group of globulins exists in wheat, some of which could be associated with the pathogenesis of T1D in some susceptible individuals. These data expand our knowledge of specific wheat globulins and will enable further elucidation of their role in wheat biology and human health. PMID:19615078

Unexpected suppression of anti-Fya and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin.

PubMed

Branch, Donald R; Scofield, Terry L; Moulds, John J; Swanson, Jane L

2011-04-01

Rh immune globulin (RhIG) has been used successfully for many years for the antenatal suppression of anti-D in D- mothers carrying D+ babies to prevent hemolytic disease of the fetus and newborn. Although the mechanism of RhIG-induced immunosuppression remains unknown, a recent report (TRANSFUSION 2006;46:1316-22) has shown that women receiving RhIG produce elevated levels of transforming growth factor (TGF)β-1, a powerful immunosuppressant cytokine. It was suggested that induction of TGFβ-1 and immunosuppression may be independent of cognate antigen recognition by RhIG. Herein, we present a description of a mother and baby that supports this hypothesis. Red blood cells and serum were analyzed using saline-tube indirect antiglobulin test methods. RhIG (RhoGAM) was administered after each amniocentesis performed at 28, 31, and 36 weeks' gestation. A group A, D-(cde), K+, Fy(a-b+), MNs, Jk(a+b+) mother with no detectable anti-D had an anti-Fy(a) titer of 4096 before RhIG but only 256 after RhIG. Mother gave birth to a group O, D-(cde), Fy(a+b+) healthy baby boy having a weak-positive direct antiglobulin test with anti-Fy(a) eluted from his cells and the titer in the cord serum was 4. This case demonstrates the potential immunosuppressive properties of RhIG for down regulation of a possible clinically significant alloantibody, not anti-D, where no D+ antigen is in the circulation of the mother. The case illustrates the potential utility for using RhIG to modulate antibody levels in situations other than for classical suppression of anti-D production. Although the mechanism in this case is unknown, TGFβ-1-mediated or antibody-mediated immunosuppression to soluble nonparticulate antigens are possible mechanisms. © 2010 American Association of Blood Banks.

Serum protein changes in immune and nonimmune pigeons infected with various strains of Trichomonas gallinae

USGS Publications Warehouse

Kocan, R.M.; Herman, C.M.

1970-01-01

Serum protein changes were studied in immune and nonimmune pigeons infected with three different strains of Trichomonas gallinae. Strain I (nonvirulent) produced no change in the relative concentration of serum components. Strains II (oral canker) and III (Jones' Barn) produced decreases in albumin and alpha globulins, and increases in beta and gamma globulins between the 7th and 20th days post infection. Birds infected with strain II began to return to normal by the 20th day, while all those infected with strain III were dead between 10 and 14 days post infection. Two serum protein patterns resulted from infection of immune birds with the Jones' Barn strain. One showed no change in relative protein concentrations and no tissue invasion by the parasite while the other was similar to that seen in nonimmune birds infected with a strain producing oral canker. These also showed evidence of tissue invasion by the parasite. It was concluded that tissue invasion was necessary to evoke a quantitative change in serum protein concentrations.

Early CMV Viremia Is Associated with Impaired Viral Control following Nonmyeloablative Hematopoietic Cell Transplantation with a Total Lymphoid Irradiation and Antithymocyte Globulin Preparative Regimen

PubMed Central

Schaenman, Joanna M.; Shashidhar, Sumana; Rhee, Chanu; Wong, Jonathan; Navato, Shelly; Wong, Ruby M.; Ho, Dora Y.; Arai, Sally; Johnston, Laura; Brown, Janice M.

2017-01-01

The reconstitution of immune function after hematopoietic cell transplant (HCT) plays an important role in the control of viral infections. Both donor and recipient cytomegalovirus (CMV) serostatus has been shown to contribute to effective immune function; however, the influence of a nonmyeloablative preparative (NMA) regimen using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) on antiviral immune reconstitution has not yet been described. In 117 recipients of NMA HCT patients following ATG and TLI, not unexpectedly, CMV viremia was seen in approximately 60% of the seropositive patients regardless of donor serostatus, and recipient seropositivity significantly increased the odds of CMV viremia after transplant in a multivariate analysis. The administration of ATG and TLI resulted in a strikingly earlier viremia in the posttransplant period when compared to the previously reported timing of viremia following myeloablative preparative regimens, especially for transplant recipients who were seropositive for CMV with seronegative donors. Furthermore, early viremia in the setting of a CMV naïve donor was associated with a delay in functional antiviral control. These observations demonstrate the dynamic nature of immunity in relation to CMV antigen exposure in the complex environment resulting from NMA conditions where both donor and residual recipient immune response affect viral control. PMID:20736077

Sex-hormone-binding globulin.

PubMed

Anderson, D C

1974-01-01

A review was made to understand how plasma binding protein might influence sex-hormone action in target tissues. Steroids are predominately bound to plasma proteins and only unbound steroids enter the cells. Sex-hormone-binding globulin (SHBG) binds to both the main circulating steroid T and E2 but changes in SHBG concentrations exert significant results. Increased SHBG levels increase estrogen production and decreases T activity; whereas, increased androgens increase T action and inhibit SHBG production. These disturbances in hormone maintenance may lead to abnormal adult sex differentiation such as hirsutism and forms of hynaecomastia. By developing SHBG concentration measurement methods-responses of hirsutism to glucocorticoid or estrogem may be assessed. In addition, the effect of thyroid hormones on SHBG may also have therapeutic implications in endocrine disease.

Clinical Reactions and Serologic Changes After the Administration of Heterologous Antilymphocyte Globulin to Human Recipients of Renal Homografts

PubMed Central

Kashiwagi, Noboru; Brantigan, Charles O.; Brettschneider, Lawrence; Groth, Carl G.; Starzl, Thomas E.

2010-01-01

Summary Clinical reactions and serologic changes after intramuscular administration of horse anti-human lymphocyte globulin (ALG) were studied in 53 human recipients of renal homografts. The ALG was used as an adjuvant immunosuppressive drug. In the usual case 47 injections were given over a 4-month period. All patients had pain, tenderness, erythema, and swelling at the injection sites. Benign systemic side effects included fever in all cases, hives in eight cases, rash in five, pruritus in five, arthralgia in three, and periorbital edema in one. Anaphylactic reactions occurred in 11 cases. These were easily treated, and there was complete recovery in every instance within 90 min. In eight of these cases the ALG administration was discontinued. Subsequent injections were given in the other three. Four of 11 patients tested had positive skin tests to ALG before therapy. Antibodies against sheep red blood cells developed during therapy in 39 of 40 patients; 10 reached titers as high as 1:128 to 1:512. Precipitin antibodies as measured with an electroimmunodiffusion technique developed in 36 of 40 patients. All three immunologic tests were of value in predicting the probability of an anaphylactic reaction, but the discrimination was imperfect Immunoelectrophoretic studies of sera from 13 patients showed antibodies to horse beta globulins in all cases, to alpha globulins in 9 cases, and to gamma globulins in only 1. This finding indicates that a safer ALG could be made by removing the trace quantities of alpha and beta globulins from the immunologically more active gamma globulins. PMID:4181614

Correlation between serum total globulins and gamma globulins and their use to diagnose failure of passive transfer in foals.

PubMed

Fouché, Nathalie; Graubner, Claudia; Howard, Judith

2014-11-01

Various assays have been used as an aid to diagnose failure of passive transfer (FPT) of immunoglobulins in neonatal foals, but often lack sensitivity as screening tests, or are time consuming to perform and impractical as confirmatory tests. The aim of the present study was to evaluate whether measurement of serum total globulins (TG; i.e. total protein minus albumin) can be used to estimate the electrophoretic gamma globulin (EGG) fraction in hospitalised neonatal foals with suspected FPT. Sample data from 56 foals were evaluated retrospectively. The coefficient of rank correlation was 0.84. The area under the curve of ROC analysis was 0.887, 0.922 and 0.930 for EGG concentrations <2 g/L, < 4 g/L and <8 g/L, respectively. Cut-offs for TG achieved ≥90% sensitivity for detecting EGG <2 g/L, < 4 g/L and <8 g/L, with negative predictive values of >97% and >94%, using prevalence of 15% and 30%, respectively. These results suggest that measurement of TG can be used as a guide to predicting EGG, provided that appropriate cut-off values are selected, and this technique could be a useful initial screening test for FPT in foals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immunity to Escherichia coli in pigs: Serum Gamma Globulin Levels, Indirect Hemagglutinating Antibody Titres and Bactericidal Activity Against E. coli in pigs up to five Weeks of Age

PubMed Central

Wilson, M. R.; Svendsen, J.

1972-01-01

Serum gamma globulin levels, indirect hemagglutinating antibody titres and bactericidal activity against the 0149:K91;K88ac:H10 Serotype of Escherichia coli were determined in pigs up to five weeks of age from vaccinated and non-vaccinated sows. Gamma globulin levels at two days of age were approximately twice adult levels, by three weeks of age they were one quarter of adult levels and remained so until five weeks of age. Indirect hemagglutinating antibody activity was highest at two days of age, fell until three weeks of age and then rose. Little or no indirect hemagglutinating antibody activity was detected in sera taken at two days of age from pigs from non-vaccinated sows. Only three of 26 two day old pigs had demonstrable bactericidal activity; by three weeks of age 16 of 26 had bactericidal activity. Serum from piglets of vaccinated sows had no more bactericidal activity than did sera from non-vaccinated sows. PMID:4110608

Comparison of cost of immune globulin intravenous therapy to conventional immunosuppressive therapy in treating patients with autoimmune mucocutaneous blistering diseases.

PubMed

Daoud, Yassine J; Amin, Ketan G

2006-04-01

Autoimmune mucocutaneous blistering diseases (AMBD) are a group of potentially fatal diseases that affect the skin and mucous membranes. AMBD have different target antigens as well as variable clinical presentation, course, and prognosis. The mainstay of conventional immunosuppressive therapy (CIST) for AMBD is long-term high-dose systemic corticosteroids and immunosuppressive agents. Such therapy has proven effective in many patients; however, in some patients, the disease continues to progress with significant sequelae such as blindness, loss of voice, anal, and vaginal stenosis which causes poor quality of life. Furthermore, the CIST may have some serious side effects including opportunistic infections which may cause death. Immune globulin intravenous (IGIV) therapy has been reportedly used in the management of patients with AMBD refractory to CIST. IGIV has shown to be more clinically beneficial than CIST by bringing about long-term clinical remission and less recurrence. The high cost of the IGIV is of concern to patients, physicians, and insurance companies. In this report, we compare the cost of IGIV to that of CIST in treating a cohort of 15 mucous membrane pemphigoid (MMP), 10 ocular cicatricial pemphigoid (OCP), 15 bullous pemphigoid (BP), and 32 pemphigus vulgaris (PV) patients. In each cohort of patients, CIST had significant side effects, many of which were hazardous and required prolonged and frequent hospitalizations. Some of these side effects were severe enough to require discontinuation of the treatment. We consider the total cost of CIST to be the actual cost of the drug, plus the cost of management of the side effects produced by CIST. In the same patient cohort, no significant side effects to IGIV were observed. None of the IGIV treated patients required physician visits, laboratory tests, or hospitalizations specifically related to IGIV therapy. Hence, the total cost of the IGIV therapy is the actual cost of the IGIV only. The mean total cost

The Effects of Environment and Physiological Cyclicity on the Immune System of Viperinae

PubMed Central

Kobolkuti, Lorand; Cadar, Daniel; Czirjak, Gabor; Niculae, Mihaela; Kiss, Timea; Sandru, Carmen; Spinu, Marina

2012-01-01

One of the important aspects of species' survival is connected with global climate changes, which also conditions the epidemiology of infectious diseases. Poikilotherms are exposed, as other species, to climatic influence, especially due to their physiological peculiarities such as important stages of their life cycle: hibernation, shedding, and active phase. The immune system serves as an accurate indicator of the health status and stress levels in these species. This study aimed to monitor the changes of innate (leukocyte subpopulations and total immune globulins) and adaptive immunity (in vitro leukocyte blast transformation) of two viper species, V. berus berus and V. ammodytes ammodytes, endemic in Europe and spread in different regions of Romania during their three major life cycles, hibernation, shedding, and active phase. The results indicated that seasonal variance and cycle rather than species and regional distribution influence the functionality of the immune system. PMID:22547989

Questioning the role of actinfree Gc-Globulin as actin scavenger in neurodegenerative central nervous system disease: relationship to S-100B levels and blood-brain barrier function.

PubMed

Gressner, Olav A; Schifflers, Marie-Claire; Kim, Philipp; Heuts, Leo; Lahme, Birgit; Gressner, Axel M

2009-02-01

Preliminary studies report on significantly higher levels of the major cytoskeleton protein actin in CSF of patients with neurodegenerative conditions and that the dynamics of these levels obviously correlates with disease progression and clinical disability. One of the primary functions of actinfree Gc-Globulin is to bind and neutralize extracellular monomeric actin, released into the circulation by necrotic or ruptured cells, and thus ameliorating the clinical outcome in situations of severe organ damage. This is the first study to investigate actinfree Gc-Globulin and S100-B levels (as reliable marker of neurodegeneration) in paired CSF and serum samples of patients with multietiological CNS diseases. 42% of all patients with CNS disease displayed serum concentrations of actinfree Gc-Globulin above the established reference range. CSF concentrations of actinfree Gc-Globulin and S100-B were positively correlated with the severity of blood-brain barrier (BBB) dysfunction. Furthermore, patients with severe BBB dysfunction presented a higher percentage of intrathecal synthesis of actinfree Gc-Globulin compared to patients with mild to moderate dysfunction and to patients with normal BBB function. Representative longitudinal data from selected patients demonstrated an inverse behaviour of actinfree Gc-Globulin and S100-B CSF concentrations, suggesting a consumption of the actin scavenger capacity of Gc-Globulin in times of increased neuronal damage. This presumption was supported by the fact that those conditions associated with a severe neuronal damage, in particular CNS trauma, and highest S100-B concentrations simultaneously displayed lowest actinfree Gc-Globulin levels, and thus residual actin binding capacity of Gc-Globulin. In summary, our data propose a function of actinfree Gc-Globulin also in the clearance of actin filaments from CSF of patients with neuronal damage. However, active recruitment of hepatic derived actinfree Gc-Globulin to the site of CNS

Ammonia concentration and relative humidity in poultry houses affect the immune response of broilers.

PubMed

Wei, F X; Hu, X F; Xu, B; Zhang, M H; Li, S Y; Sun, Q Y; Lin, P

2015-04-10

To investigate the effect of ammonia (NH3) and humidity on the immune response of broilers, broilers were exposed to 30 or 70 mg/kg atmospheric NH3 for 21 days. Additionally, birds were exposed to 35, 60, and 85% relative humidity (RH). The relative weights of lymphoid organs, serum total protein, serum globulin, serum albumin, serum lysozyme, proliferation index of peripheral blood lymphocytes, and splenic cytokine gene expression were determined. Exposure to 70 mg/kg NH3 decreased the relative weight of the spleen during the experimental period, serum lysozyme concentration in the first and second weeks, and serum globulin concentration in the third week. The proliferation of peripheral blood lymphocytes was reduced. High levels of NH3 caused increase in IL-1β gene expression in the experimental period and IL-4 gene expression in the first week. Birds exposed to 85% RH had lower thymus and bursa of Fabricius weights in the third week and serum lysozyme concentration in the first week; IL-1β and IL-4 expressions were higher in the second and third weeks and first and second weeks, respectively, than in birds exposed to 60% RH. IL-4 expression was lower during the first week, and IL-1β expression was higher during the second week with 35% RH than with 60% RH. In conclusion, high NH3 level in the poultry house suppressed the immune response of broiler chickens. Neither high nor low RH benefited the immune response of broilers. Furthermore, there was an interactive effect between NH3 and RH on the immune response of broilers.

Tissue-specific and hormonally regulated expression of a rat alpha 2u globulin gene in transgenic mice.

PubMed Central

Soares, V da C; Gubits, R M; Feigelson, P; Costantini, F

1987-01-01

To investigate the tissue-specific and hormonal regulation of the rat alpha 2u globulin gene family, we introduced one cloned member of the gene family into the mouse germ line and studied its expression in the resulting transgenic mice. Alpha 2u globulingene 207 was microinjected on a 7-kilobase DNA fragment, and four transgenic lines were analyzed. The transgene was expressed at very high levels, specifically in the liver and the preputial gland of adult male mice. The expression in male liver was first detected at puberty, and no expression was detected in female transgenic mice. This pattern of expression is similar to the expression of endogenous alpha 2u globulin genes in the rat but differs from the expression of the homologous mouse major urinary protein (MUP) gene family in that MUPs are synthesized in female liver and not in the male preputial gland. We conclude that these differences between rat alpha 2u globulin and mouse MUP gene expression are due to evolutionary differences in cis-acting regulatory elements. The expression of the alpha 2u globulin transgene in the liver was abolished by castration and fully restored after testosterone replacement. The expression could also be induced in the livers of female mice by treatment with either testosterone or dexamethasone, following ovariectomy and adrenalectomy. Therefore, the cis-acting elements responsible for regulation by these two hormones, as well as those responsible for tissue-specific expression, are closely linked to the alpha 2u globulin gene. Images PMID:2446121

Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity.

PubMed

Charbonneau, M; Strasser, J; Lock, E A; Turner, M J; Swenberg, J A

1989-06-01

Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet formation and cell proliferation in male but not in female rat kidneys. These protein droplets contained, alpha 2u-globulin, a male rat-specific low-molecular-weight protein and 2,4,4-trimethyl-2-pentanol, a metabolite of TMP that was reversibly bound to this protein. Studies were undertaken to determine if 1,4-DCB produced similar effects; 1,2-DCB was used for comparison since it did not produce renal carcinogenesis in male rats. Gel filtration chromatography of a 116,000g supernatant prepared from kidneys of 1,4-[14C]DCB-treated rats showed that radiolabel coeluted with alpha 2u-globulin as one sharp peak as opposed to a multipeak pattern observed for 1,2-[14C]DCB; the maximal quantity of radiolabel for 1,4-DCB was twice that for 1,2-DCB. Equilibrium dialysis of kidney cytosol in the presence or absence of sodium dodecyl sulfate demonstrated that the radiolabel was reversibly bound to alpha 2u-globulin; the amount for 1,4-[14C]DCB-treated rats was almost twice as much as that for 1,2-[14C]DCB-treated rats. 1,2-DCB was also shown to be covalently bound to renal alpha 2u-globulin, and covalently bound to liver and plasma high-molecular-weight proteins. 1,4-DCB and, to a minor extent, 2,5-dichlorophenol, the major metabolite of 1,4-DCB, were reversibly bound to renal alpha 2u-globulin from 1,4-DCB-treated rats. 1,4-DCB increased protein droplet formation in male but not in female rat kidneys, whereas equimolar doses of 1,2-DCB showed no effect in either sex. Renal cell proliferation, measured by [3H]thymidine incorporation into renal DNA, was increased after 1,4-DCB but not after 1,2-DCB treatment. Nephrotoxicity and biochemical alterations induced by

Overestimation of Albumin Measured by Bromocresol Green vs Bromocresol Purple Method: Influence of Acute-Phase Globulins.

PubMed

Garcia Moreira, Vanessa; Beridze Vaktangova, Nana; Martinez Gago, Maria Dolores; Laborda Gonzalez, Belen; Garcia Alonso, Sara; Fernandez Rodriguez, Eloy

2018-05-22

Usually serum albumin is measured with dye-binding assay as bromocresol green (BCG) and bromocresol purple (BCP) methods. The aim of this paper was to examine the differences in albumin measurements between the Advia2400 BCG method (AlbBCG), Dimension RxL BCP (AlbBCP) and capillary zone electrophoresis (CZE). Albumin concentrations from 165 serum samples were analysed using AlbBCG, AlbBCP and CZE. CZE was employed to estimate different serum protein fractions. Influence of globulins on albumin concentration discrepancies between methods was estimated as well as the impact of the albumin method on aCa concentrations. Medcalc was employed for statistical analysis, setting a value of P < 0.05 as significant. Correlation of AlbBCG and AlbBCP was r = 0.948 (p < 0.0001), but mean difference was large. Bland-Altman plots showed greater bias at lower albumin concentrations. AlbBCG were positively biased versus CZE (3.54 g/L). There was good agreement between CZE and ALbBCP (< 1 g/L). The AlbBCG assay bias shows a good correlation with alpha-1-globulin concentrations (r = 0.758); moderate and weak correlations were observed with CRP (r = 0.729) and alpha-2-globulin (r = 0.585); we found no correlation with beta-globulin (r = 0.120) or gamma-globulin (r = -0.303). Mean aCa based on AlbBCG and AlbBCP methods were 2.34 ± 0.15 mmol/L and 2.46 ± 0.16 mmol/L (p < 0.01), with a mean BCG-BCP difference of -0.12. Albumin results from the BCP and BCG methods may result in unacceptable differences and clinical confusion, especially at lower albumin concentrations. Serum acute phase proteins contribute to overestimating the albumin concentration using AlbBCG.

Sensitization with 7S globulins from peanut, hazelnut, soy or pea induces IgE with different biological activities which are modified by soy tolerance.

PubMed

Kroghsbo, Stine; Bøgh, Katrine L; Rigby, Neil M; Mills, E N Clare; Rogers, Adrian; Madsen, Charlotte B

2011-01-01

It is not known why some foods sensitizing via the gastrointestinal tract are prevalent allergenic foods and others are not. Eating habits, processing, and the food matrix have been suggested to influence the allergenicity of a given food. Factors related to protein structure, such as stability to digestion, have also been suggested. 7S globulins from peanut, hazelnut, soy, and pea were studied to determine whether related proteins would induce a similar sensitization when removed from their 'normal' matrix. Brown Norway rats (soy tolerant or nontolerant) were immunized i.p. 3 times with 100 μg purified peanut, hazelnut, soy, or pea 7S without adjuvant. Sera were analyzed for specific antibodies by different ELISAs (IgG1, IgG2a, and IgE), inhibition ELISA, and rat basophilic leukemia cell assay. The 4 related 7S globulins induced a response with an almost identical level of specific antibodies, but peanut 7S induced IgE of higher avidity than hazelnut and pea 7S which, again, had a higher avidity than IgE induced by soy 7S. Soy tolerance reduced the functionality of IgE without influencing antibody titers. Although the 4 7S globulins are structurally related allergens, they induce antibodies with different antigen-binding characteristics. Peanut 7S induces IgE of a higher avidity than hazelnut and pea 7S which, again, has a higher avidity than IgE induced by soy 7S. We also show that soy tolerance influences the function of antibodies to peanut 7S. These findings may help explain how antibodies of different clinical significances can develop in different individuals sensitized to the same allergen. Copyright © 2011 S. Karger AG, Basel.

Posttransplant Immune Activation: Innocent Bystander or Insidious Culprit of Posttransplant Accelerated Atherosclerosis.

PubMed

Ducloux, Didier; Bamoulid, Jamal; Crepin, Thomas; Rebibou, Jean-Michel; Courivaud, Cecile; Saas, Philippe

2017-09-01

Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8 + T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8 + T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence.

Nutritional and physiological responses of young growing rats to diets containing raw cowpea seed meal, protein isolate (globulins), or starch.

PubMed

Olivera, Leticia; Canul, Rossana Rodriguez; Pereira-Pacheco, Fabiola; Cockburn, Joanna; Soldani, Florinda; McKenzie, Norma H; Duncan, Michelle; Olvera-Novoa, Miguel A; Grant, George

2003-01-01

The nutritional and physiological effects of raw cowpea (Vigna unguiculata (L) Walp.) seed meal, protein isolate (globulins), or starch on the metabolism of young growing rats have been evaluated in 14-day trials. Wet and dry weight gain, feed conversion efficiency, and lipid and protein accretion were significantly reduced as a result of inclusion of seed meal, globulins, or starch in the diet, with growth retardation being most marked with the seed meal. The proportional weights of the small intestine and pancreas were increased by meal diets, and serum cholesterol levels were slightly reduced. The globulins and raw starch also increased relative small intestine weights but had no effect on the pancreas or serum constituents. The effects of cowpeas on rats appeared to be due primarily to the combined actions of globulins, resistant starches, protease inhibitors, and possibly fiber and non-starch polysaccharides on intestinal and systemic metabolism.

Rapid changes in the serum total protein and globulin levels in complications caused by facultatively pathogenic Gram-negative bacteria.

PubMed

Petrás, G; Kiss, S; Juraszek, J; Merétey, K

1978-01-01

The changes in the levels of total protein and four globulin fractions were followed up throughout the entire course of complications caused by Gram-negative facultative pathogens in 37 acute cases of respiratory insufficiency accompanying different underlying illnesses and in 9 chronic, bedridden patients given artificial ventilation. At the onset of the infectious complications, in the first place in septic shock, the levels of various globulin fractions showed a decrease corresponding to a half-life of 2 to 4 days. Neither the increased catabolism, nor the protein losses by the urine and tracheal secretions offer a sufficient explanation for the escape of globulins of this extent from the plasma. It seems that this is a consequence of the increase in capillary permeability due to the effect of antigen-antibody reactions and that of endotoxin. As a result, in the critical phase of the infectious complications, at the point of culmination, e.g. in septic shock, diminished amount of different globulins is transported to the site of utilization, that is, to the inflammatory area.

Modification of solubility and heat-induced gelation of amaranth 11S globulin by protein engineering.

PubMed

Carrazco-Peña, Laura; Osuna-Castro, Juan A; De León-Rodríguez, Antonio; Maruyama, Nobuyuki; Toro-Vazquez, Jorge F; Morales-Rueda, Juan A; Barba de la Rosa, Ana P

2013-04-10

The primary structure of amaranth 11S globulin (Ah11S) was engineered with the aim to improve its functional properties. Four continuous methionines were inserted in variable region V, obtaining the Ah11Sr+4M construction. Changes on protein structure and surface characteristics were analyzed in silico. Solubility and heat-induced gelation of recombinant amaranth 11S proglobulin (Ah11Sr and Ah11Sr+4M) were compared with the native protein (Ah11Sn) purified from amaranth seed flour. The Ah11Sr+4 M showed the highest surface hydrophobicity, but as consequence the solubility was reduced. At low ionic strength (μ = 0.2) and acidic pH (<4.1), the recombinant proteins Ah11Sr and Ah11Sr+4 M had the highest and lowest solubility values, respectively. All globulins samples formed gels at 90 °C and low ionic strength, but Ah11Sn produced the weakest and Ah11Sr the strongest gels. Differential scanning calorimetry analysis under gel forming conditions revealed only exothermic transitions for all amaranth 11S globulins analyzed. In conclusion, the 3D structure analysis has revealed interesting molecular features that could explain the thermal resistance and gel forming ability of amaranth 11S globulins. The incorporation of four continuous methionines in amaranth increased the hydrophobicity, and self-supporting gels formed had intermediate hardness between Ah11Sn and Ah11Sr. These functional properties could be used in the food industry for the development of new products based on amaranth proteins.

Clinical mimics of infant botulism.

PubMed

Francisco, Ann Marie O; Arnon, Stephen S

2007-04-01

Since 1992, Human Botulism Immune Globulin has been provided by the California Department of Health Services to infants with probable infant botulism, the intestinal toxemia form of human botulism. Human Botulism Immune Globulin became available in California in 1992-1997 within a randomized, controlled, double-blinded, pivotal clinical trial and subsequently became available nationwide in 1998-2003 in an open-label study until its licensure in October 2003 as BabyBIG. Thereafter, Human Botulism Immune Globulin remained available nationwide as an approved orphan-drug product. To achieve prompt neutralization of circulating botulinum toxin, the decision to treat with Human Botulism Immune Globulin has been based on clinical criteria that include a consistent history and physical findings of bulbar palsies, hypotonia, and weakness. After licensure, the charts of patients who did not have laboratory-confirmed infant botulism were reviewed to identify their actual diagnoses. The approximately 5% of 681 patients treated with Human Botulism Immune Globulin who did not have infant botulism fell into 5 categories: spinal muscular atrophy, metabolic disorders, other infectious diseases, miscellaneous, and probable infant botulism lacking laboratory confirmation.

The Plasma Disappearance Time and Catabolic Half-Life of I 131-Labelled Normal Human Gamma Globulin in Amyloidosis and in Rheumatoid Arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mills, John A.; Calkins, Evan; Cohen, Alan S.

1961-10-01

The serum survival time and catabclic half-life of intravenously injected I 131-labeled pooled human gamma globulin - were studied in three patients with amyloidosis, four patients with rheumatoid arthritis, and three normal controls. The half-time of gamma globulin survival in the controsubjects ranged from 16.5 to 30 days. Two patients with amyloidosis, one primary and one secondary, both with the nephrotic syndrome, exhibited shortened serum half-times of 4.5 and 11 days, respectively. The serum half-time of the latter patient, before the appearance of clinical amyloidosis, was 14 days. One patient with primary amyloidosis but without nephrosis exhibited a half-time ofmore » serum gamma globulin disappearance of 21 days. The half-time of gamma globulin disappearance in four patients with chronic active rheumatoid arthritis varied between 19.5 and 8.5 days. The lower figure was found in a patient having a high titer of rheumatoid factor. If this subject is excepted, the average half- time in three rheumatoid subjects is 17 days. The catabolic half-life of the iodinated gamma globulin agreed in most instances with the serum half-time. The calculated distribution space of the injected gamma globulin showed no consistent alteration in either amyloidosis or rheumatoid arthritis as compared with the control subjects. Since the nephrotic syndrome from other causes may produce an accelerated catabolic half-life, a similar finding on these subjects cannot be ascribed to amyloidosis.« less

EVOLUTION OF THE IMMUNE RESPONSE

PubMed Central

Papermaster, Ben W.; Condie, Richard M.; Finstad, Joanne; Good, Robert A.

1964-01-01

the hagfish has no bands with mobilities of mammalian gamma globulins; that the lamprey has a single, relatively faint band of this type; and that multiple gamma bands are characteristic of the holostean, elasmobranchs, and teleosts studied. By this method of study, the bowfin appeared to have substantial amounts of gamma2 globulin. 7. We conclude that adaptive immunity and its cellular and humoral correlates developed in the lowest vertebrates, and that a rising level of immunologic reactivity and an increasingly differentiated and complex immunologic mechanism are observed going up the phylogenetic scale from the hagfish, to the lamprey, to the elasmobranchs, to the holosteans, and finally the teleosts. PMID:14113107

Clinical experience with thymoglobulin and antithymocyte globulin-Fresenius as induction therapy in renal transplant patients: a retrospective study.

PubMed

Cicora, Federico; Mos, Fernando; Paz, Marta; Roberti, Javier

2013-10-01

We describe our experiences with, and compare the outcomes of, 2 groups of renal transplant patients treated with thymoglobulin or antithymocyte globulin-Fresenius as induction therapy at transplant to reduce the incidence of acute rejection and prevent delayed allograft function. Twenty-four recipients of deceased-donor or living-donor kidney transplants received thymoglobulin, and 23 patients received antithymocyte globulin-Fresenius. Patient and graft survival and efficacy and safety were assessed at 3 months. The demographic characteristics of both groups were comparable, but the predominant donor type was significantly different. Incidence of complications, delayed graft function, and creatinine concentrations were comparable in both groups. At 3 months after the transplant, patient survival rate was 92% in the thymoglobulin group and 96% in the antithymocyte globulin-Fresenius group (P > .05), and death-censored graft survival rate for both groups was not significantly different. Average hematocrit and lymphocyte, neutrophil, and platelet counts were comparable in both groups at 3 months' follow-up. Average white blood count at 1 month was significantly different between the groups: at 5.62 ± 2.45 × 103 cells/mm³ in the thymoglobulin group and 7.85 ± 4.10 × 103 cells/mm³ in the ATG-F group (P < .05). Considering the study design limitations, we observed that our group of treated patients, safety, and efficacy of thymoglobulin and antithymocyte globulin-Fresenius were generally comparable.

Synthesis of Globulins in Maize Embryos 1

PubMed Central

Kriz, Alan L.; Schwartz, Drew

1986-01-01

The two major components of the globulin fraction in Zea mays embryos are specified by the Prot gene. Pulse-chase analysis of protein synthesis in cultured, immature embryos indicates that the smaller Prot-specific polypeptide, PROT, is derived from the larger polypeptide, PROT'. These experiments also demonstrate that PROT' is derived from a short-lived precursor polypeptide, prePROT'. The primary Prot-specific translation product, as detected by in vitro translation of immature embryo RNA, is of a lower apparent molecular weight than pre-PROT', suggesting the involvement of co- and/or post-translational modification in the production of prePROT'. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:16665136

Use of Recombinant Factor VIIa in a Pediatric Patient With Initial Presentation of Refractory Acute Immune Thrombocytopenic Purpura and Severe Bleeding

PubMed Central

Gurion, Reut; Siu, Anita; Weiss, Aaron R.; Masterson, Margaret

2012-01-01

Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications. PMID:23258971

Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

PubMed Central

Baron, Frédéric; Mohty, Mohamad; Blaise, Didier; Socié, Gérard; Labopin, Myriam; Esteve, Jordi; Ciceri, Fabio; Giebel, Sebastian; Gorin, Norbert Claude; Savani, Bipin N; Schmid, Christoph; Nagler, Arnon

2017-01-01

Allogeneic hematopoietic stem cell transplantation is increasingly used as treatment for patients with life-threatening blood diseases. Its curative potential is largely based on immune-mediated graft-versus-leukemia effects caused by donor T cells contained in the graft. Unfortunately, donor T cells are also the cause of graft-versus-host disease. The vast majority of human leukocyte antigen-matched allogeneic hematopoietic stem cell transplants are nowadays carried out with peripheral blood stem cells as the stem cell source. In comparison with bone marrows, peripheral blood stem cells contain more hematopoietic stem/progenitor cells but also one log more T cells. Consequently, the use of peripheral blood stem cells instead of bone marrow has been associated with faster hematologic recovery and a lower risk of relapse in patients with advanced disease, but also with a higher incidence of chronic graft-versus-host disease. These observations have been the basis for several studies aimed at assessing the impact of immunoregulation with anti-thymocyte globulin on transplantation outcomes in patients given human leukocyte antigen-matched peripheral blood stem cells from related or unrelated donors. After a brief introduction on anti-thymocyte globulin, this article reviews recent studies assessing the impact of anti-thymocyte globulin on transplantation outcomes in patients given peripheral blood stem cells from human leukocyte antigen-matched related or unrelated donors as well as in recipients of grafts from human leukocyte antigen haploidentical donors. PMID:27927772

Treatment of aplastic anaemia with lower-dose anti-thymocyte globulin produces similar response rates and survival as per standard dose anti-thymocyte globulin schedules.

PubMed

Scott, A; Morris, K; Butler, J; Mills, A K; Kennedy, G A

2016-10-01

Aplastic anaemia (AA) is a rare acquired bone marrow failure syndrome resulting from the immune-mediated destruction of haemopoietic stem cells. For adults in whom first-line haemopoietic progenitor cell transplantation is not feasible, combination anti-thymocyte globulin (ATGAM) plus cyclosporine A is standard therapy; however, there are minimal data available regarding the optimal ATGAM dosage in terms of efficacy and survival. Our institutions have historically used different dosing protocols of ATGAM in the treatment of AA. We aimed to review the outcome of AA patients treated with these protocols and compare them to the published literature. We conducted a retrospective study of 31 adults who received first-line ATGAM for AA and compared response rates and survival between cohorts who received standard (40 mg/kg/day D1-4) versus lower-dose (15 mg/kg/day D1-5) ATGAM schedules. There were similar rates of response (64 vs 71%, P = 1.0), relapse (33 vs 33%, P = 1.0), transformation (14 vs 24%, P = 0.66) or infection (43 vs 47%, P = 1.0), respectively, between standard and lower-dose cohorts. At a median follow up of 24 months, there was no statistical difference between standard and lower-dose cohorts in either event-free (42.2 vs 64.7%, P = 0.91) or overall survival (73.1 vs 88.2%, P = 0.75). Our experience suggests that lower-dose ATGAM at 15 mg/kg/day D1-5 as treatment of AA produces similar responses and outcomes as per standard-dose ATGAM schedules. Prospective trials comparing ATGAM dose schedules in AA are warranted. © 2016 Royal Australasian College of Physicians.

d-Limonene-induced male rat-specific nephrotoxicity: Evaluation of the association between d-limonene and alpha 2u-globulin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lehman-McKeeman, L.D.; Rodriguez, P.A.; Takigiku, R.

1989-06-15

d-Limonene is a naturally occurring monoterpene, which when dosed orally, causes a male rat-specific nephrotoxicity manifested acutely as the exacerbation of protein droplets in proximal tubule cells. Experiments were conducted to examine the retention of (/sup 14/C)d-limonene in male and female rat kidney, to determine whether d-limonene or one or more of its metabolites associates with the male rat-specific protein, alpha 2u-globulin, and if so, to identify the bound material. The results indicated that, 24 hr after oral administration of 3 mmol d-limonene/kg, the renal concentration of d-limonene equivalents was approximately 2.5 times higher in male rats than in femalemore » rats. Equilibrium dialysis in the presence or absence of sodium dodecyl sulfate indicated that approximately 40% of the d-limonene equivalents in male rat kidney associated with proteins in a reversible manner, whereas no significant association was observed between d-limonene equivalents and female rat kidney proteins. Association between d-limonene and male rat kidney proteins was characterized by high-performance gel filtration and reverse-phase chromatography. Gel filtration HPLC indicated that d-limonene in male rat kidney is associated with a protein fraction having a molecular weight of approximately 20,000. Separation of alpha 2u-globulin from other kidney proteins by reverse-phase HPLC indicated that d-limonene associated with a protein present only in male rat kidney which was definitively identified as alpha 2u-globulin by amino acid sequencing. The major metabolite associated with alpha 2u-globulin was d-limonene-1,2-oxide. Parent d-limonene was also identified as a minor component in the alpha 2u-globulin fraction.« less

Control of adhesion of human induced pluripotent stem cells to plasma-patterned polydimethylsiloxane coated with vitronectin and γ-globulin.

PubMed

Yamada, Ryotaro; Hattori, Koji; Tachikawa, Saoko; Tagaya, Motohiro; Sasaki, Toru; Sugiura, Shinji; Kanamori, Toshiyuki; Ohnuma, Kiyoshi

2014-09-01

Human induced pluripotent stem cells (hiPSCs) are a promising source of cells for medical applications. Recently, the development of polydimethylsiloxane (PDMS) microdevices to control the microenvironment of hiPSCs has been extensively studied. PDMS surfaces are often treated with low-pressure air plasma to facilitate protein adsorption and cell adhesion. However, undefined molecules present in the serum and extracellular matrix used to culture cells complicate the study of cell adhesion. Here, we studied the effects of vitronectin and γ-globulin on hiPSC adhesion to plasma-treated and untreated PDMS surfaces under defined culture conditions. We chose these proteins because they have opposite properties: vitronectin mediates hiPSC attachment to hydrophilic siliceous surfaces, whereas γ-globulin is adsorbed by hydrophobic surfaces and does not mediate cell adhesion. Immunostaining showed that, when applied separately, vitronectin and γ-globulin were adsorbed by both plasma-treated and untreated PDMS surfaces. In contrast, when PDMS surfaces were exposed to a mixture of the two proteins, vitronectin was preferentially adsorbed onto plasma-treated surfaces, whereas γ-globulin was adsorbed onto untreated surfaces. Human iPSCs adhered to the vitronectin-rich plasma-treated surfaces but not to the γ-globulin-rich untreated surfaces. On the basis of these results, we used perforated masks to prepare plasma-patterned PDMS substrates, which were then used to pattern hiPSCs. The patterned hiPSCs expressed undifferentiated-cell markers and did not escape from the patterned area for at least 7 days. The patterned PDMS could be stored for up to 6 days before hiPSCs were plated. We believe that our results will be useful for the development of hiPSC microdevices. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

11S Storage globulin from pumpkin seeds: regularities of proteolysis by papain.

PubMed

Rudakova, A S; Rudakov, S V; Kakhovskaya, I A; Shutov, A D

2014-08-01

Limited proteolysis of the α- and β-chains and deep cleavage of the αβ-subunits by the cooperative (one-by-one) mechanism was observed in the course of papain hydrolysis of cucurbitin, an 11S storage globulin from seeds of the pumpkin Cucurbita maxima. An independent analysis of the kinetics of the limited and cooperative proteolyses revealed that the reaction occurs in two successive steps. In the first step, limited proteolysis consisting of detachments of short terminal peptides from the α- and β-chains was observed. The cooperative proteolysis, which occurs as a pseudo-first order reaction, started at the second step. Therefore, the limited proteolysis at the first step plays a regulatory role, impacting the rate of deep degradation of cucurbitin molecules by the cooperative mechanism. Structural alterations of cucurbitin induced by limited proteolysis are suggested to generate its susceptibility to cooperative proteolysis. These alterations are tentatively discussed on the basis of the tertiary structure of the cucurbitin subunit pdb|2EVX in comparison with previously obtained data on features of degradation of soybean 11S globulin hydrolyzed by papain.

Using Changes in Binding Globulins to Assess Oral Contraceptive Compliance

PubMed Central

Westhoff, Carolyn; Petrie, K.A.; Cremers, S.

2012-01-01

Background Validity of oral contraceptive pill (OCP) clinical trial results depends on participant compliance. Ethinyl estradiol (EE2) induces increases in hepatic binding globulin (BG) levels. Measuring these BG increases may provide an effective and convenient approach to distinguishing non-compliant from compliant OCP users in research settings. This analysis evaluated the usefulness of measuring increases in corticosteroid, sex hormone and thyroxine binding globulins (CBG, SHBG, TBG) as measures of OCP compliance. Methods We used frozen serum from a trial that compared ovarian suppression between normal weight and obese women randomized to one of two OCPs containing EE2 and levonorgestrel (LNG). Based on serial LNG measurements during the trial, 17% of participants were non-compliant. We matched non-compliant participants with compliant participants by age, BMI, ethnicity and OCP formulation. We measured CBG, SHBG and TBG levels, and compared change from baseline to 3-month follow-up between the non-compliant and compliant participants. Construction of receiver operator characteristic (ROC) curves allowed comparison of various BG measures. Results Changes in CBG and TBG distinguished OCP non-compliant users from compliant users (area under the ROC curve (AUROC), 0.86 and 0.89, p < 0.01). Changes in SHBG were less discriminating (AUROC 0.69) Conclusions EE2 induced increases in CBG and TBG provide a sensitive integrated marker of compliance with an LNG-containing OCP. PMID:22795088

Hericium caput-medusae (Bull.:Fr.) Pers. polysaccharide enhance innate immune response, immune-related genes expression and disease resistance against Aeromonas hydrophila in grass carp (Ctenopharyngodon idella).

PubMed

Gou, Changlong; Wang, Jiazhen; Wang, Yuqiong; Dong, Wenlong; Shan, Xiaofeng; Lou, Yujie; Gao, Yunhang

2018-01-01

The objective was to add 0, 400, 800 or 1200 mg/kg of Hericium caput-medusae polysaccharide (HCMP) to the basal diet of grass carp (Ctenopharyngodon idella) and determine effects on humoral innate immunity, expression of immune-related genes and disease resistance. Adding HCMP enhanced (P < 0.05) bactericidal activity at 1, 2 and 3 weeks and also lysozyme activity, complement C3, and SOD activity at 2 and 3 weeks. Supplementing 800 or 1200 mg/kg of HCMP for 2 or 3 weeks increased (P < 0.05) serum concentrations of total protein, albumin and globulin. Two immune-related genes (IL-1β and TNF-α) were up-regulated (P < 0.05) in HCMP supplemented groups given 800 or 1200 mg/kg HCMP after 2 and 3 weeks of feeding. Expression of anti-inflammatory cytokine IL-10 was down-regulated (P < 0.05) after receiving 800 or 1200 mg/kg HCMP for 2 or 3 weeks. Fish fed 800 mg/kg HCMP had maximal disease resistance against Aeromonas hydrophila (65.4%). In conclusion, HCMP enhanced immune response and expression of immune-related genes and increased disease resistance against Aeromonas hydrophila in grass carp, with greatest effects in fish given 800 mg/kg HCMP for 3 weeks. Copyright © 2017 Elsevier Ltd. All rights reserved.

The diagnostic value of a globulin/platelet model for evaluating liver fibrosis in chronic hepatitis B patients.

PubMed

Coskun, Banu Demet; Altinkaya, Engin; Sevinc, Eylem; Ozen, Mustafa; Karaman, Hatice; Karaman, Ahmet; Poyrazoglu, Orhan

2015-12-01

Liver biopsy, which is considered the best method for evaluating hepatic fibrosis, has important adverse events. Therefore, non-invasive tests have been developed to determine the degree of hepatic fibrosis in patients with chronic hepatitis B. To verify the usefulness of a new fibrosis index the globulin/platelet model in patients with chronic hepatitis B and to compare it with other noninvasive tests for predicting significant fibrosis. This study was the second to evaluate the globulin/platelet model in HBV patients. We retrospectively investigated 228 patients with chronic hepatitis B who performed liver biopsy from 2013 to 2014. The globulin/platelet model, APGA [AST/Platelet/Gamma-glutamyl transpeptidase/Alfa-fetoprotein], FIB4, fibrosis index, cirrhosis discriminate score, and Fibro-quotient were calculated, and the diagnostic accuracies of all of the fibrosis indices were compared between the F0-2 (no-mild fibrosis) and F3-6 (significant fibrosis) groups. All of the noninvasive markers were significantly correlated with the stage of liver fibrosis (p < 0,001). To predict significant fibrosis (F ≥ 3), the area under the curve (95% CI) was found to be greatest for APGA (0.83 [0.74-0.86]), followed by FIB-4 (0.75[0.69-0.80]), the globulin/platelet model (0.74 [0.68-0.79]), fibrosis index (0.72 [0.6-0.78], cirrhosis discriminate score (0.71 [0.64-0.76]) and Fibro-quotient (0.62 [0.55-0.7]). The area under the receiver operating characteristic curves of APGA was significantly higher than that of the other noninvasive fibrosis markers (p < 0.05). While the APGA index was found to be the most valuable test for the prediction significant fibrosis in patients with chronic hepatitis B, GP model was the thirth valuable test. Therefore, we recommended that APGA could be used instead of the GP model for prediction liver fibrosis.

Small GTPase Sar1 is crucial for proglutelin and α-globulin export from the endoplasmic reticulum in rice endosperm.

PubMed

Tian, Lihong; Dai, Ling Ling; Yin, Zhi Jie; Fukuda, Masako; Kumamaru, Toshihiro; Dong, Xiang Bai; Xu, Xiu Ping; Qu, Le Qing

2013-07-01

Rice seed storage proteins glutelin and α-globulin are synthesized in the endoplasmic reticulum (ER) and deposited in protein storage vacuoles (PSVs). Sar1, a small GTPase, acts as a molecular switch to regulate the assembly of coat protein complex II, which exports secretory protein from the ER to the Golgi apparatus. To reveal the route by which glutelin and α-globulin exit the ER, four putative Sar1 genes (OsSar1a/b/c/d) were cloned from rice, and transgenic rice were generated with Sar1 overexpressed or suppressed by RNA interference (RNAi) specifically in the endosperm under the control of the rice glutelin promoter. Overexpression or suppression of any OsSar1 did not alter the phenotype. However, simultaneous knockdown of OsSar1a/b/c resulted in floury and shrunken seeds, with an increased level of glutelin precursor and decreased level of the mature α- and β-subunit. OsSar1abc RNAi endosperm generated numerous, spherical, novel protein bodies with highly electron-dense matrixes containing both glutelin and α-globulin. Notably, the novel protein bodies were surrounded by ribosomes, showing that they were derived from the ER. Some of the ER-derived dense protein bodies were attached to a blebbing structure containing prolamin. These results indicated that OsSar1a/b/c play a crucial role in storage proteins exiting from the ER, with functional redundancy in rice endosperm, and glutelin and α-globulin transported together from the ER to the Golgi apparatus by a pathway mediated by coat protein complex II.

From glanders to globulins: A study in comparative medicine.

PubMed

Watkins, P E

2017-05-01

The anti-globulin test was described in 1945, and ever since has been synonymous with the lead author, Robin Coombs, a young veterinary surgeon, at that time embarking on a career in immunological research. This was marked by a number of important contributions in the field, including the description and categorisation of hypersensitivity reactions, co-authored with Philip Gell. Together they wrote the classical text, Clinical Aspects of Immunology, which has been updated and republished over the ensuing 50 years. Although Robin Coombs is best remembered for his contributions to medical immunology, he made a number of significant early advances in the field of veterinary immunology.

Antitumor effect of degalactosylated gc-globulin on orthotopic grafted lung cancer in mice.

PubMed

Hirota, Keiji; Nakagawa, Yoshinori; Takeuchi, Ryota; Uto, Yoshihiro; Hori, Hitoshi; Onizuka, Shinya; Terada, Hiroshi

2013-07-01

Group-specific component (Gc)-globulin-derived macrophage-activating factor (GcMAF) generated by a cascade of catalytic reactions with deglycosidase enzymes exerts antitumor activity. We hypothesized that degalactosyl Gc-globulin (DG3), a precursor of GcMAF, also plays a role in recovery from cancer as well as GcMAF due to progression of deglycosylation by generally resident sialidases and mannosidases. We prepared the subtypes of DG3, such as 1f1f and 1s1s and its 22 homodimers, by using vitamin D3-binding Sepharose CL-6B and examined their antitumor activity in mice bearing Lewis lung carcinoma cells, by counting the number of nodules formed in their lungs. Antitumor activity of DG3 was observed regardless of its subtype, being equivalent to that of GcMAF. The injection route of DG3 affected its antitumor activity, with subcutaneous and intramuscular administration being more favorable than the intraperitoneal or intravenous route. In order to obtain significant antitumor activity, more than 160 ng/kg of DG3 were required. DG3 proved to be promising as an antitumor agent, similarly to GcMAF.

THE EMERGENCE OF ANTIBODIES WITH EITHER IDENTICAL OR UNRELATED INDIVIDUAL ANTIGENIC SPECIFICITY DURING REPEATED IMMUNIZATIONS WITH STREPTOCOCCAL VACCINES

PubMed Central

Eichmann, Klaus; Braun, Dietmar G.; Feizi, Ten; Krause, Richard M.

1970-01-01

Electrophoretically monodisperse antibody components in rabbit antisera to the carbohydrates of the Groups A and C streptococci have been examined for their individual antigenic specificity. In these antibody components which were isolated by preparative electrophoresis, individual antigenic specificity was confined to the specific antibody and was absent in the nonantibody γ-globulin. Radioprecipitation experiments and the use of immune absorbent columns constructed from goat anti-antisera, which had been absorbed with fraction II, revealed that all the specific antibody in an electrophoretically monodisperse component was reactive with the homologous anti-antibody. Antibodies with either identical or distinct individual antigenic specificities may occur in the same rabbit with repeated immunizations. Antibodies with identical antigenic specificity had identical electrophoretic mobility, whereas antibodies with unrelated antigenic specificities had distinct electrophoretic mobilities. In the interval between immunizations, if antibody to the carbohydrate antigen was absent, there was no detectable antibody with individual antigenic specificity. PMID:4192569

The effect of antilymphocytic antibody on the humoral immune response in different strains of mice

PubMed Central

Ghaffar, A.; James, K.

1973-01-01

The effect of a single batch of horse anti-mouse thymocyte globulin on the immune response to type III polysaccharide antigen has been investigated in 2–3-month-old male A/HeJ, C57B1, BALB/c, DBA/1, CBA and C3H mice. In almost all cases the intraperitoneal administration of 5 mg of this material on days –4 and –2 significantly suppressed the immune response to 0.1, 1.0 and 5.0 μg of antigen injected i.v. on day 0. Further studies undertaken in BALB/c mice indicated that effective suppression of the immune response to type III polysaccharide antigen could also be achieved by injecting 5 mg of this product (i.p.) some 15–30 minutes prior to antigenic challenge. Preliminary cell reconstitution studies in antilymphocytic antibody-treated CBA mice indicate that the ability to respond to type III polysaccharide can be partially restored by the injection of syngeneic thymocytes, bone marrow cells or spleen cells. PMID:4146227

Immune and hormonal activity in adults suffering from depression.

PubMed

Nunes, S O V; Reiche, E M V; Morimoto, H K; Matsuo, T; Itano, E N; Xavier, E C D; Yamashita, C M; Vieira, V R; Menoli, A V; Silva, S S; Costa, F B; Reiche, F V; Silva, F L V; Kaminami, M S

2002-05-01

An association between depression and altered immune and hormonal systems has been suggested by the results of many studies. In the present study we carried out immune and hormonal measurements in 40 non-medicated, ambulatory adult patients with depression determined by CID-10 criteria and compared with 34 healthy nondepressed subjects. The severity of the condition was determined with the Hamilton Depression Rating Scale. Of 40 depressed patients, 31 had very severe and 9 severe or moderate depression, 29 (72.5%) were females and 11 (27.5%) were males (2.6:1 ratio). The results revealed a significant reduction of albumin and elevation of alpha-1, alpha-2 and beta-globulins, and soluble IL-2 receptor in patients with depression compared to the values obtained for nondepressed subjects (P<0.05). The decrease lymphocyte proliferation in response to a mitogen was significantly lower in severely or moderately depressed patients when compared to control (P<0.05). These data confirm the immunological disturbance of acute phase proteins and cellular immune response in patients with depression. Other results may be explained by a variety of interacting factors such as number of patients, age, sex, and the nature, severity and/or duration of depression. Thus, the data obtained should be interpreted with caution and the precise clinical relevance of these findings requires further investigation.

Structure of γ-conglutin: insight into the quaternary structure of 7S basic globulins from legumes.

PubMed

Czubinski, Jaroslaw; Barciszewski, Jakub; Gilski, Miroslaw; Szpotkowski, Kamil; Debski, Janusz; Lampart-Szczapa, Eleonora; Jaskolski, Mariusz

2015-02-01

γ-Conglutin from lupin seeds is an unusual 7S basic globulin protein. It is capable of reducing glycaemia in mammals, but the structural basis of this activity is not known. γ-Conglutin shares a high level of structural homology with glycoside hydrolase inhibitor proteins, although it lacks any kind of inhibitory activity against plant cell-wall degradation enzymes. In addition, γ-conglutin displays a less pronounced structural similarity to pepsin-like aspartic proteases, but it is proteolytically dysfunctional. Only one structural study of a legume 7S basic globulin, that isolated from soybean, has been reported to date. The quaternary assembly of soybean 7S basic globulin (Bg7S) is arranged as a cruciform-shaped tetramer comprised of two superposed dimers. Here, the crystal structure of γ-conglutin isolated from Lupinus angustifolius seeds (LangC) is presented. The polypeptide chain of LangC is post-translationally cleaved into α and β subunits but retains its covalent integrity owing to a disulfide bridge. The protomers of LangC undergo an intricate quaternary assembly, resulting in a ring-like hexamer with noncrystallographic D3 symmetry. The twofold-related dimers are similar to those in Bg7S but their assembly is different as a consequence of mutations in a β-strand that is involved in intermolecular β-sheet formation in γ-conglutin. Structural elucidation of γ-conglutin will help to explain its physiological role, especially in the evolutionary context, and will guide further research into the hypoglycaemic activity of this protein in humans, with potential consequences for novel antidiabetic therapies.

Resolution of Mild Ganciclovir-Resistant Cytomegalovirus Disease with Reduced-Dose Cidofovir and CMV-Hyperimmune Globulin.

PubMed

Patel, Samir J; Kuten, Samantha A; Knight, Richard J; Hong, Dana M; Gaber, A Osama

2014-01-01

Ganciclovir-resistant cytomegalovirus (CMV) is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by "indirect" viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative) kidney transplant patients diagnosed with ganciclovir-resistant CMV disease. All patients initially developed "breakthrough" viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2 mg/kg) cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV.

RhD isoimmunization and current management modalities.

PubMed

Neal, J L

2001-01-01

To review the literature on current perspectives and treatment of RhD isoimmunization. A search was conducted on MEDLINE and CINAHL, and supplemental articles/ bulletins were obtained from cited references and the Web site of the American College of Obstetricians and Gynecologists. Recent texts also were reviewed. Key search words: isoimmunization, Rho (d) immune globulin, fetal erythroblastosis, intrauterine blood transfusions, alloimmunization. Articles and comprehensive works from indexed journals in the English language relevant to key words and published after 1995 were evaluated. Historically relevant periodicals and texts were also reviewed and selected. Data were extracted and organized under the following headings: testing of the antepartum patient, antepartum treatment of isoimmunization, testing of the postpartum patient, anti-D immune globulin, antepartum anti-D immune globulin prophylaxis, other antepartum and obstetric indications for anti-D immune globulin administration, postpartum anti-D immune globulin prophylaxis, nursing implications, and future possibilities. RhD isoimmunized pregnancies continue to contribute to worldwide perinatal and neonatal morbidity and mortality. This review describes the basic knowledge necessary to care for these pregnancies and the current management modalities. The management options for RhD compromised gestations continue to evolve almost as quickly as technological advances are made. Multiple areas of research in this field have surfaced, and nurses can become valuable members of these research teams. The literature also indicates that with the available knowledge and resources, the current rate of RhD isoimmunization can be further decreased with closer adherence to proposed management guidelines by all health care professionals.

International reference reagents: antihuman globulin. An ISBT/ICSH joint working party report. International Society of Blood Transfusion. International Committee for Standardization in Haematology.

PubMed

Case, J; Ford, D S; Chung, A; Collins, R; Kochman, S; Mazda, T; Overbeeke, M; Perera, R; Sakuldamrongpanich, T; Scott, M; Voak, D; Zupańska, B

1999-01-01

An international working party has conducted a study designed to select a suitable reference reagent for antihuman globulin, to replace those first made available in 1987. The chosen preparation contains levels of anti-IgG and anti-C3 (anti-C3c and anti-C3d) potency that are considered suitable to serve for reference when evaluating either polyspecific antihuman globulin reagents or those containing their separate monospecific components. The reference material is available in 2-ml freeze-dried aliquots from seven assigned distribution centres.

The effect of induction therapy on established CMV specific T cell immunity in living donor kidney transplantation.

PubMed

Stranavova, L; Hruba, P; Girmanova, E; Tycova, I; Slavcev, A; Fronek, J; Slatinska, J; Reinke, P; Volk, H-D; Viklicky, O

2018-05-04

Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation. Recipients' peripheral blood mononuclear cells were stimulated with immediate-early (IE1) and phosphoprotein 65 (pp65) CMV-derived peptide pools and the number of cells producing interferon gamma (IFN-gamma) was assessed. Patients received quadruple immunosuppression based either on depletive rabbit antithymocyte globulin (rATG) or non-depletive basiliximab induction and tacrolimus/mycophenolate mofetil/steroids. Patients with rATG induction received valgancyclovir prophylaxis. No effects of different induction agents on CMV specific T cell immunity were found at sixth month after kidney transplantation. There were no associations among dialysis vintage, pretransplant CMV specific T cell immunity, and later CMV DNAemia. Similarly, no effect of CMV prophylaxis on CMV specific T cell immunity was revealed. This study shows no effect of posttransplant immunosuppression on CMV specific T cell immunity in living donor kidney transplant recipients with CMV immunity already established, regardless of lymphocyte depletion and CMV prophylaxis.

[Influence of water fluoride exposure on sex hormone binding globulin and testosterone in adult male].

PubMed

Zhou, Tong; Yang, Rupu; Li, Shihong; Zheng, Guoqing; Xi, Yu; Cheng, Xuemin; Hou, Jiaxiang; Cui, Liuxin; Ba, Yue

2013-03-01

To explore the influence of water fluoride exposure on sex hormone binding globulin (SHBG) and testosterone in adult male. Cross-sectional study was conducted in three villages of Tongxu county including high fluoride group (HFG), defluoridation project group (DFPG) and control group (CG) based on the fluoride concentration in drinking water. Adult male who were born and raised in the village and aged 18 - 50 years old were recruited using cluster sampling. Fasting blood and morning urine samples were collected. The fluoride levels in drinking water and urine were detected by fluoride-ion selective electrode method. Serum SHBG level was determined using enzyme-linked immunosorbent assay (ELISA). The chemical luminescence immune analysis method was used to detect serum testosterone content. Serum SHBG level was 47.85 nmol/L in CG, 31.37 nmol/L in DFPG and 24.52 nmol/L in HFG respectively. There were significant difference among of three groups (P < 0.05). Serum testosterone level was 3.69 ng/ml in CG, 4.61 ng/ml in DFPG and 4.83 ng/ml in HFG respectively. Serum testosterone level in HFG was significantly higher than that in CG (P < 0.05). Serum SHBG level in HFG has positive correlation with serum testosterone (r = 0.230, P = 0.049), which has not been observed in DFPG and CG. Long-time fluorine exposure may affect serum SHBG and testosterone level in adult male.

[Effect of specific antibodies on active immunity development in those inoculated with an antirabies vaccine].

PubMed

Kravchenko, A T; Latypova, R G; Morpgova, V M; Movsesiants, A A

1980-11-01

The study of the effect of gamma globulin introduced in different doses (0.5 and 0.25 ml/mg) in combination with Fermi rabies vaccine (observations on humans were made) and with cerebral rabies vaccine inactivated by UV irradiation (in animal experiments) demonstrated that the injection of the higher doses of gamma globulin resulted in lower geometrical mean of antibody titers. Therefore, in combined administration of rabies vaccine and gamma globulin for postexposure rabies prevention it is advisable to reduce the dose of gamma globulin by one-half.

Immune-directed therapy for type 1 diabetes at the clinical level: the Immune Tolerance Network (ITN) experience.

PubMed

Ehlers, Mario R; Nepom, Gerald T

2012-01-01

Reestablishing immune tolerance in type 1 diabetes (T1D), a chronic autoimmune disease, is a major goal. The Immune Tolerance Network (ITN) has initiated eight clinical trials of immunomodulatory therapies in recent-onset T1D over the past decade. Results have been mixed in terms of clinical efficacy, but the studies have provided valuable mechanistic insight that are enhancing our understanding of the disease and guiding the design of future trials. Trials of non-Fc-binding anti-CD3 mAbs have revealed that modulation of this target leads to partial responses, and ITN's AbATE trial led to identification of a robust responder group that could be distinguished from non-responders by baseline metabolic and immunologic features. A pilot study of the combination of IL-2 and rapamycin gave the first demonstration that frequency and function of regulatory T cells (Tregs) can be enhanced in T1D subjects, although the therapy triggered the activation of effectors with transient β-cell dysfunction. Similarly, therapy with anti-thymocyte globulin led to substantial lymphocyte depletion, but also to the activation of the acute-phase response with no clinical benefit during preliminary analyses. These and other results provide mechanistic tools that can be used as biomarkers for safety and efficacy in future trials. Furthermore, our results, together with those of other organizations, notably TrialNet, delineate the roles of the major components of the immune response in T1D. This information is setting the stage for future combination therapy trials. The development of disease-relevant biomarkers will also enable the implementation of innovative trial designs, notably adaptive trials, which will increase efficiencies in terms of study duration and sample size, and which will expedite the conduct of trials in which there are uncertainties about dose response and effect size.

Determining the time androgens and sex hormone-binding globulin take to return to baseline after discontinuation of oral contraceptives in women with polycystic ovary syndrome: a prospective study.

PubMed

Sánchez, Luis A; Pérez, Marilda; Centeno, Indira; David, Marisa; Kahi, Doris; Gutierrez, Elizabeth

2007-03-01

In this study, discontinuation of oral contraceptive pills in women with polycystic ovary syndrome was followed by the return of all measured androgens and sex hormone-binding globulin levels to basal values after 8 weeks. These observations are pertinent to the measurement of androgens and sex hormone-binding globulin levels in subjects who currently are taking oral contraceptive pills and have symptoms that are related to polycystic ovary syndrome.

Anthrax Vaccination and Self-reported Symptoms, Functional Status, and Medical Conditions in the National Health Survey of Gulf War Era Veterans and Their Families

DTIC Science & Technology

2003-04-01

botulism, immune globulin , plague, and meningncocu.s). Among the 11,441 Culf War veterans, a total of 4601 Gulf veterans (40.2%)) self-reported (S-R...administered (typhoid, borulinum toxoid, immune globulin , plague, and meningococus). This variable was coded as the sum of the number of vaccines...parametric Wilcoxon signecl- ranks test was used to assess whether the prc\\lalencc in S-R yes group was the same as the prevalcncc in the S-R n o

[FAB immunoglobulin fragments. I. The comparative characteristics of the serological and virus-neutralizing properties of a gamma globulin against tick-borne encephalitis and of the FAB fragments isolated from it].

PubMed

Barban, P S; Minaeva, V M; Pantiukhina, A N; Startseva, M G

1976-06-01

A comparative study was made of the serological properties and virus-neutralizing activity of antiencephalitis gamma-globulin and Fab-fragments isolated from it by gel-filtration. Horse immunoglobulins against the autumno-summer tick-borne encephalitis virus could be disintegrated with the aid of papaine to monovalent Fab-fragments which (according to the complement fixation reaction, the test of suppression of the complement fixation, and the HAIT) retained the serological activity whose level was compared with that of the serological activity of gamma-globulin. Fab-fragments possessed a marked virus-neutralizing activity. The mean value of a logarithm of the neutralization index was 2.65 +/- 0.2 for Fab-fragments and 3.74 +/- 0.38 for gamma-globulin (P less than 0.01).

Response to phytohaemagglutinin of lymphocytes from mice treated with anti-lymphocyte globulin

PubMed Central

Tursi, A.; Greaves, M. F.; Torrigiani, G.; Playfair, J. H. L.; Roitt, I. M.

1969-01-01

Thymus, spleen, lymph node and peripheral blood lymphocytes taken from mice treated with anti-lymphocyte globulin (ALG) showed a greatly diminished response to PHA in vitro. Recovery of circulating lymphocyte levels preceded recovery of responsiveness to PHA. The latter could be prevented by reinjection of ALG or by thymectomy. Grafts were rejected within a period equal to the normal rejection time after PHA responsiveness had recovered to a value of approximately 20 per cent of the normal. Thus the effect of ALG on thymus dependent lymphocytes in mice can be monitored by assessing the PHA sensitivity of peripheral white blood cells. ImagesFIG. 1 PMID:4900922

Combination of lamivudine and adefovir without hepatitis B immune globulin is safe and effective prophylaxis against hepatitis B virus recurrence in hepatitis B surface antigen-positive liver transplant candidates.

PubMed

Gane, Edward J; Patterson, Scott; Strasser, Simone I; McCaughan, Geoffrey W; Angus, Peter W

2013-03-01

Without effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related liver disease is frequently complicated by severe and rapidly progressive HBV recurrence. Combination prophylaxis with hepatitis B immune globulin (HBIG) and lamivudine (LAM) reduces long-term recurrence rates below 10%; however, HBIG is costly and inconvenient to administer. We, therefore, conducted a multicenter, prospective study of outcomes with an HBIG-sparing regimen of LAM plus adefovir dipivoxil (ADV) initiated at the time of listing for liver transplantation and continued after transplantation. Twenty-six patients were recruited into this study at the time of listing for transplantation, and 20 subsequently underwent transplantation. Twelve of the 26 patients had LAM exposure before the study baseline, but none had LAM resistance. The median HBV viral load before the institution of antiviral therapy was approximately 4.0 log(10) IU/mL (range=2.3-7.5 log(10) IU/mL). To the 20 patients who underwent transplantation, 800 IU of intramuscular HBIG was given immediately after transplantation and daily for 7 days only (total HBIG dose=6400 IU). All transplant patients remained alive without HBV recurrence (they were negative for hepatitis B surface antigen, and HBV DNA was undetectable) after a median follow-up of 57 months after transplantation (range=27-83 months). The median serum creatinine level in these patients rose from 81 to 119 μmol/L over the course of the study. No patient required dose reduction or cessation. After the completion of this prospective study, the regimen was modified so that no perioperative HBIG was administered if the pretransplant serum HBV DNA level was suppressed below 3 log(10) IU/mL. Another 28 patients with HBV-related liver disease underwent transplantation (18 without HBIG). All remained alive and well without HBV recurrence after a median follow-up of 22 months after transplantation (range=10-58 months). In conclusion, a combination of

Dissociation, aggregation of sesame alpha-globulin in nonionic detergent solution.

PubMed

Lakshmi, T S; Nandi, P K

1978-10-01

Nonionic detergents Triton X-100 and Brij 36T induce dissociation and aggregation of the protein sesame alpha-globulin above the critical micelle concentrations (cmc) of the detergents. Spectrophotometric titration in Triton shows no change in the pKInt value of the tyrosyl groups at 1x10-3 M detergent where both dissociation and aggregation of the protein are observed. Fluorescence measurement does not indicate any change in the environment of the tryptophan groups of the protein in Brij. Viscosity measurements show no major conformational change of the protein in the detergent solution. Binding measurements suggest that perhaps micelles of the detergent predominantly bind to the protein. The detergent micelles preferentially bind to the exposed hydrophobic surfaces of the protein subunits. The association of the protein detergent complex through electrostatic interaction is probably responsible for the formation of the aggregates.

Changes in the waking-sleeping behavior after albumin or $gamma$ globulin injection to lethally irradiated rats (in French)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maigrot, J.C.; Cier, A.; Riotte, M.

1973-01-01

Studies were performed on chronically implanted rats. These rats were subjected to whole-body irradiations of 950 rads (LD 100% 6 days). The following reproducible changes were observed: serious nonreversible disturbances in the waking-sleeping behavior, manifested principally by an almost complete disappearance of paradoxical sleep 4 days after the exposure. The intraperitioneal administration, 4 to 5 days after irradiation of one or several 250mg doses of gamma -globulin enabled the rats to recover both quantitatively and qualitatively a paradoxical sleep identical to that observed with nonirradiated animals during 2 to 3 days. On the other hand when gamma globulins are injectedmore » into nonirradiated animals, the PS level does not alter in any significant way. In addition, injections of human albumin serum carried out under the same experimental conditions, appear to modify EEG parameters, which have been disturbed by irradiation as well as producing a significant improvement in the general state of the irradiated animal, this being confirmed by the prolonged survival time observed. (FR)« less

RhIG for the treatment of immune thrombocytopenia: consensus and controversy

PubMed Central

Despotovic, Jenny M.; Lambert, Michele P.; Herman, Jay H.; Gernsheimer, Terry B.; McCrae, Keith R.; Tarantino, Michael D.; Bussel, James B.

2012-01-01

Anti-D immune globulin (RhIG) is a front-line option in North America for the treatment of immune thrombocytopenia (ITP) in children and adults. Recently, addition of a Food and Drug Administration-mandated black box warning highlighted the risks of intravascular hemolysis, renal failure, and disseminated intravascular coagulation after anti-D infusion, prompting concern within the medical community regarding its use. A working group convened in response to this warning to prepare a consensus document regarding the safety of RhIG because there has been no increased incidence of adverse events since the initial discovery of these reactions many years ago. The efficacy of anti-D is well documented and only briefly reviewed. The estimated incidence and proposed mechanisms for the rare, major treatment-related complications are discussed, and signal detection data associated with heightened risk of acute hemolytic reactions are presented. The importance of considering host factors, given the rarity of severe reactions, is emphasized. Safety profiles of parallel treatment options are reviewed. The working group consensus is that RhIG has comparable safety and efficacy to other front-line agents for the treatment of children and adults with ITP. Safety may be further improved by careful patient selection. PMID:21981825

COMPLEMENT FIXATION IN DISEASED TISSUES

PubMed Central

Burkholder, Peter M.

1961-01-01

An immunohistologic complement fixation test has been used in an effort to detect immune complexes in sections of kidney from rats injected with rabbit anti-rat kidney serum and in sections of biopsied kidneys from four humans with membranous glomerulonephritis. Sections of the rat and human kidneys were treated with fluorescein-conjugated anti-rabbit globulin or antihuman globulin respectively. Adjacent sections in each case were incubated first with fresh guinea pig serum and then in a second step were treated with fluorescein-conjugated antibodies against fixed guinea pig complement to detect sites of fixation of the complement. It was demonstrated that the sites of rabbit globulin in glomerular capillary walls of the rat kidneys and the sites of localized human globulin in thickened glomerular capillary walls and swollen glomerular endothelial cells of the human kidneys were the same sites in which guinea pig complement was fixed in vitro. It was concluded from these studies that rabbit nephrotoxic antibodies localize in rat glomeruli in complement-fixing antigen-antibody complexes. Furthermore, it was concluded that the deposits of human globulin in the glomeruli of the human kidneys behaved like antibody globulin in complement-fixing antigen-antibody complexes. The significance of demonstrating complement-fixing immune complexes in certain diseased tissues is discussed in regard to determination of the causative role of allergic reactions in disease. PMID:19867205

Differential representation of albumins and globulins during grain development in durum wheat and its possible functional consequences.

PubMed

Arena, Simona; D'Ambrosio, Chiara; Vitale, Monica; Mazzeo, Fiorella; Mamone, Gianfranco; Di Stasio, Luigia; Maccaferri, Marco; Curci, Pasquale Luca; Sonnante, Gabriella; Zambrano, Nicola; Scaloni, Andrea

2017-06-06

Durum wheat (Triticum turgidum ssp. durum (Desf.) Husn.) is an economically important crop used for the production of semolina, which is the basis of pasta and other food products. Its grains provide proteins and starch for human consumption. Grain development is a key process in wheat physiology; it is highly affected by a number of enzymes that control the metabolic processes governing accumulation of starch and storage proteins and ultimately grain weight. Most of these enzymes are present in the albumin/globulin grain fraction, which represents about a quarter of total seed proteins. With the aim to describe the dynamic profile of the albumin/globulin fraction during durum wheat grain development, we performed a proteomic analysis of this subproteome using a two-dimensional differential gel electrophoresis (2D-DIGE)-based approach and compared six developmental stages. A total of 285 differentially (237 over- and 48 under-) represented spots was identified by nanoLC-ESI-LIT-MS/MS, which were associated with 217 non-redundant Triticum sequence entries. Quantitative protein dynamics demonstrated that carbon metabolism, energy, protein destination/storage, disease/defense and cell growth/division functional categories were highly affected during grain development, concomitantly with progressive grain size increase and starch/protein reserve accumulation. Bioinformatic interaction prediction revealed a complex network of differentially represented proteins mainly centered at enzymes involved in carbon and protein metabolism. A description of 18 proteins associated with wheat flour human allergies was also obtained; these components showed augmented levels at the last developmental stages. By providing a comprehensive understanding of the molecular basis of durum wheat grain development, yield and quality formation, this study provides the foundation and reveals potential biomarkers for further investigations of durum wheat breeding and semolina quality. A 2D

Use of the Vettest 8008 and refractometry for determination of total protein, albumin, and globulin concentrations in feline effusions.

PubMed

Papasouliotis, Kostas; Murphy, Kate; Dodkin, Steve; Torrance, Andy G

2002-01-01

Pleural and peritoneal effusion is a common clinical finding in feline practice. Determination of fluid albumin (ALB) and globulin (GLOB) concentrations in addition to total protein (TP) concentration can be helpful in diagnosing or ruling out certain diseases in cats, especially feline infectious peritonitis (FIP). The objective of this study was to compare effusion TP, ALB, and GLOB results obtained by a refractometer and a bench-top dry chemistry analyzer with those results obtained by a reference method. Twenty-six pleural and 14 peritoneal effusion samples were analyzed from 40 cats with various diseases. TP and ALB concentrations were determined by a reference automated wet chemistry analyzer (Kone Specific, Kone Instruments, Espoo, Finland), a bench-top dry chemistry analyzer (Vettest 8008, IDEXX Laboratories Ltd, Chalfont St Peter, UK), and a refractometer (Atago SPR-T2, Atago Co, Tokyo, Japan). GLOB, albumin to globulin (A/G) ratio, and globulins as a percentage of total proteins (GLOB%) were calculated. Results were analyzed by paired t tests, difference plots, and Deming s regression analysis. Correlation coefficients (r) for TP with Vettest versus Kone and refractometer versus Kone methods were.97 and.94, respectively. GLOB and GLOB% values were significantly higher and A/G ratios were significantly lower with Vettest versus Kone methods. Correlation coefficients for ALB, GLOB, GLOB% and A/G ratio with Vettest versus Kone methods were.86,.93,.82, and.73, respectively. Although correlation with other methods was good, the refractometer underestimated TP concentrations in 3 samples. The refractometer is an acceptable method for determination of TP concentration in feline effusions. The Vettest 8008 also is an acceptable method for the determination of TP and ALB concentrations, however, calculated A/G ratios obtained with the Vettest are unacceptable.

Kinetic of the CMV-specific T-cell immune response and CMV infection in CMV-seropositive kidney transplant recipients receiving rabbit anti-thymocyte globulin induction therapy: A pilot study.

PubMed

Martín-Gandul, Cecilia; Pérez-Romero, Pilar; Mena-Romo, Damián; Molina-Ortega, Alejandro; González-Roncero, Francisco M; Suñer, Marta; Bernal, Gabriel; Cordero, Elisa

2018-03-23

Some studies have suggested that rATG treatment may be associated with an increased incidence of CMV infection and delayed CMV immune response. However, the evidences supporting this matter are scarce. This study aims to characterize the kinetic of the CMV-specific T-cell immune response before and after rATG induction therapy and the relationship with the development of CMV infection in CMV-seropositive kidney transplant recipients. An observational prospective study of CMV-seropositive kidney transplant patients that received rATG induction therapy was performed. A pretransplant sample was obtained before the surgery to determine the CMV-specific immunity. CMV viral load (by PCR) and CMV-specific T-cell immune response (by flow cytometry) were determined during the follow-up at 0.5, 1, 2, 3, 6, and 12 months post transplantation. A total of 23 patients were included in the study. CMV prophylaxis was administrated for a media of 90 days after transplantation. At the end of follow-up, 18 (78.3%) patients had CMV-specific immunity with a median value of 0.31% CD8 + CD69 + INF-γ + T cells at a median of 16 weeks post transplantation. Five patients never acquired CMV-specific immunity. No statistically significant association between CMV infection and CMV-specific T-cell immune response (P = .086) was observed. However, patients with positive pretransplant CMV-specific immunity developed earlier immunity and achieved higher levels of CD8 + CD69 + INF-γ+ T-cell post-transplantation than patients with negative pretransplant immunity. CMV-specific immune monitoring in addition to CMV-serology may be useful to stratify patient's risk of CMV infection before transplantation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immunohistochemical analysis of human milk fat globulin expression in extramammary Paget's disease.

PubMed

Ohnishi, T; Watanabe, S

2001-03-01

Primary extramammary Paget's disease is thought to be an intraepidermal carcinoma indicating apocrine secretory differentiation. In addition to expression in breast tissue, human milk fat globulin (HMFG) is expressed in the normal apocrine glands and tumours with apocrine differentiation. In this study HMFG expression in extramammary Paget's disease was analysed immunohistochemically in 18 cases of primary extramammary Paget's disease and two cases of secondary extramammary Paget's disease. The proportion and staining pattern of positive tumour cells with the anti-HMFG antibody was variable in each case. Cytoplasmic staining was observed frequently in dermal invasion and metastasis of Paget cells. The variabilities were thought to be due to modulation of the cellular localization of the cell surface component, HMFG, according to changes in cellular differentiation or malignant potency.

Treatment of US crotalidae bites: comparisons of serum and globulin-based polyvalent and antigen-binding fragment antivenins.

PubMed

Seger, Donna; Kahn, Stephen; Krenzelok, Edward P

2005-01-01

In the US, two antivenins are marketed for the treatment of snake envenomation. The horse-derived serum-globulin-based Antivenin (Crotalidae) Polyvalent (ACP) has been available since 1954. There are few data on the efficacy and incidence of adverse events that occur following the administration of ACP. Most of the data are retrospective, anecdotal, or case reports. In 2000, ovine-derived serum-globulin-based ACP (Crofab) became available. Crofab is said to cause fewer reactions than ACP, but there are few comparative data to substantiate this claim. Although both antivenins ameliorate the systemic symptoms following snake envenomation, the efficacy of either antivenin in decreasing oedema and swelling is unknown for a number of reasons. Clinical trials are small and have not included control arms. The degree of oedema, as well as the efficacy of the antivenin in decreasing oedema, may depend on the genera of the snake (usually unknown) that envenomated the patient. This article compares available data on clinical aspects of the two antivenins. More prospective data are needed to determine the comparative efficacy of the two antivenins, or the efficacy of Crofab in preventing tissue oedema. There are still unanswered questions regarding the optimal dosing regimen of Crofab.

Modified immunosuppressive therapy with porcine antilymphocyte globulin plus delayed cyclosporine A in children with severe aplastic anemia.

PubMed

Cui, Qingya; Sha, Pingping; Chen, Haifei; Shen, Hongshi; Qin, Longmei; Li, Zhengyang; Wu, Tianqin; Wang, Zhaoyue

2018-01-01

Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CsA) is the standard treatment for children with severe aplastic anemia (SAA) with no human leukocyte antigen-matched siblings. Due to the unavailability of horse ATG in China, porcine antilymphocyte globulin (p-ALG), which is less expensive and more effective than rabbit ATG, is widely used. We sought to evaluate the efficacy and safety profile of modified IST with p-ALG plus delayed CsA at day 21 in 50 SAA children. Eighteen SAA patients who progressed from nonsevere aplastic anemia (NSAA) were classified as SAA-II; the other 32 patients were classified as SAA-I. Overall response (OR) rates at 3, 6 and 12 months were 56, 64 and 62%, respectively. The 10-year overall survival (OS) rate and disease-free survival (DFS) rate were 80 and 56%. The OR, OS and DFS rates in the SAA-I group were clearly better than those in the SAA-II group. Death rate from infection within 30 days was 4%. Modified IST with p-ALG plus delayed CsA is a reliable and well-tolerated treatment for children with SAA, and reduces early death due to infection. Modified IST is more suitable for children with SAA-I.

Influence of antigen on immune complex behavior in mice.

PubMed

Finbloom, D S; Magilavy, D B; Harford, J B; Rifai, A; Plotz, P H

1981-07-01

To explore the possibility that the behavior of immune complexes can, under some circumstances, be directed by the antigen, we have studied the behavior of complexes of identical size made with the glycoproteins, orosomucoid (OR), and ceruloplasmin: or with their desialylated derivatives, asialo-orosomucoid (ASOR) and asialo-ceruloplasmin. Such desialylated proteins are rapidly removed from the circulation by a hepatic cell receptor for galactose, the sugar exposed upon removal of sialic acid. Mixtures of 125I-goat anti-ASOR with either ASOR or OR and mixtures of 125I-rabbit anti-OR with either ASOR or OR form complexes identically. The complexes were separated by density gradient centrifugation and injected intravenously into C3H mice. Blood clearance and hepatic uptake of the OR complexes and ASOR complexes were markedly different. T 1/2 for the goat OR complexes exceeded 300 min, whereas that for the ASOR complexes was 15 min. More detailed studies using rabbit complexes of various sizes revealed that light rabbit complexes behaved similarly to the goat complexes. The light rabbit OR complexes were cleared slowly, with only 18% found in the liver at 60 min, whereas the light rabbit ASOR complexes were cleared much more rapidly, with 62% found within the liver by 30 min. This rapid clearance was completely suppressed by a prior injection of a blocking dose of ASOR, which implies uptake by a galactose-mediated mechanism on hepatocytes. As the size of the rabbit complexes increased, so did the rate of Fc receptor-mediated clearance. Heavy rabbit OR complexes were cleared more rapidly than light OR complexes but not so rapidly as heavy ASOR complexes. The clearance and hepatic uptake of the heavy OR complexes were markedly suppressed by a prior injection of heat-aggregated gamma globulin, a known Fc receptor-blocking agent (45% hepatic uptake without and 6% with aggregated gamma globulin). The heavy rabbit ASOR complexes exhibited inhibition of blood clearance and

Shared decision making in the management of children with newly diagnosed immune thrombocytopenia.

PubMed

Beck, Carolyn E; Boydell, Katherine M; Stasiulis, Elaine; Blanchette, Victor S; Llewellyn-Thomas, Hilary; Birken, Catherine S; Breakey, Vicky R; Parkin, Patricia C

2014-10-01

This study aimed to examine the treatment decision-making process for children hospitalized with newly diagnosed immune thrombocytopenia (ITP). Using focus groups, we studied children with ITP, parents of children with ITP, and health care professionals, inquiring about participants' experience with decision support and decision making in newly diagnosed ITP. Data were examined using thematic analysis. Themes that emerged from children were feelings of "anxiety, fear, and confusion"; the need to "understand information"; and "treatment choice," the experience of which was age dependent. For parents, "anxiety, fear, and confusion" was a dominant theme; "treatment choice" revealed that participants felt directed toward intravenous immune globulin (IVIG) for initial treatment. For health care professionals, "comfort level" highlighted factors contributing to professionals' comfort with offering options; "assumptions" were made about parental desire for participation in shared decision making (SDM) and parental acceptance of treatment options; "providing information" was informative regarding modes of facilitating SDM; and "treatment choice" revealed a discrepancy between current practice (directed toward IVIG) and the ideal of SDM. At our center, families of children with newly diagnosed ITP are not experiencing SDM. Our findings support the implementation of SDM to facilitate patient-centered care for the management of pediatric ITP.

A portion of heifers attaining “early puberty” do not display estrus, are anovulatory and have altered sex hormone binding globulin concentrations

USDA-ARS?s Scientific Manuscript database

Cows with excess androstenedione (High A4) in the follicular fluid of dominant follicles attain puberty earlier than their low androstenedione counterparts. Furthermore, High A4 cows are anovulatory (chronic or sporadic) and have lower Sex Hormone Binding Globulin (SHBG) compared to Low A4 ovulator...

Immune complex orchitis in vasectomized rabbits

PubMed Central

1976-01-01

The results of the present study show that bilaterally vasectomized rabbits with high levels of antibodies to sperm antigens frequently develop an orchitis associated with granular deposits of rabbit IgG and C3 in the basement membranes of seminiferous tubules. The immune deposits correspond in location to electron-opaque deposits seen by electron microscopy. The "membranous orchitis" is characterized by thickening of tubular basement membranes, acc-mulation of macrophages and a few polymorphonuclear leukocytes, and destruction of the basal lamina, of the Sertoli and spermatogenetic cells. The pathogenetic role of the immune deposits and the possibility that they contain antigen- antibody complexes is indicated by: (a) selective accumulation of IgG and C3 granular deposits along the basement membranes of seminiferous tubules in rabbits producing high and persistent levels of antibodies to sperm antigens; (b) the elution of immunoglobulins from tissues with chaotropic ion-containing buffers, acid buffers, or heat; (c) the observation that the immuno-globulins accumulated in the testis contain antibody to sperm antigens; and (d) the demonstration of sperm antigens in a location similar to that of IgG and C3. It is postulated that sperm antigen-antibody complexes are formed in the basement membranes of seminiferous tubules when antigens leaking out of the tubules react with specific antibody coming from the circulation. In two rabbits with higher levels of circulating antisperm antibodies and severe orchitis, granular deposits of IgG and C3 were also present in renal glomeruli. Immunoglobulins eluted from the kidneys contained antibody with antisperm activity. These findings are consistent with the hypothesis that in some vasectomized rabbits extratesticular lesions may develop by a mechanism comparable to that of chronic serum sickness. PMID:129498

Role of the eosinophil in serum-mediated adherence of equine leukocytes to infective larvae of Strongylus vulgaris.

PubMed

Klei, T R; Chapman, M R; Dennis, V A

1992-06-01

The adherence of equine leukocytes to Strongylus vulgaris infective larvae (L3) in the presence of normal and immune sera was examined in vitro. Immune sera promoted adherence of buffy coat cells from ponies with S. vulgaris-induced eosinophilia (eosinophilic ponies) to S. vulgaris L3. However, eosinophils in the buffy coat cells were the predominant adherent cell type. Studies using leukocyte populations enriched for eosinophils, neutrophils, and mononuclear cells from eosinophilic ponies support the observations using buffy coat cells that eosinophils were the main effector cells. Adherent eosinophils from eosinophilic ponies immobilized L3. Neutrophils were less adherent and did not immobilize L3. Mononuclear cells failed to adhere. Normal eosinophils from strongly-naive ponies did not immobilize S. vulgaris L3 in the presence of immune serum, suggesting the in vivo activation of eosinophils in eosinophilic animals. Immune serum promoted less adherence of buffy coat cells to Strongylus edentatus or mixed species of Cyathostominae L3, suggesting that the serum-mediated cellular adherence phenomenon was species-specific. Normal serum promoted less cellular adherence to S. vulgaris L3 than immune serum. The adherence mediated by normal serum was removed by heat inactivation, suggesting that this nonspecific phenomenon was a complement-mediated reaction. Immune globulins promoted reactions similar to that seen using heat-inactivated immune serum, whereas normal globulins did not promote adherence. Immune globulins absorbed with pieces of S. vulgaris adult worms did not promote the adherence of buffy coat cells to S. vulgaris L3, suggesting that adult and L3 stages share antigens important in this phenomenon that resulted in the removal of specific adherence antibody during absorption.

General and Virus-Specific Immune Cell Reconstitution Following Double Cord Blood Transplantation

PubMed Central

Saliba, Rima M.; Rezvani, Katayoun; Leen, Ann; Jorgensen, Jeffrey; Shah, Nina; Hosing, Chitra; Parmar, Simrit; Oran, Betul; Olson, Amanda; Mehta, Rohtesh S.; Chemaly, Roy F.; Saunders, Ila M.; Bollard, Catherine M.; Shpall, Elizabeth J.

2015-01-01

Cord blood transplantation (CBT) is curative for many patients with hematologic malignancies but is associated with delayed immune recovery and an increased risk of viral infections compared to human leukocyte antigen (HLA) matched bone marrow or peripheral blood progenitor cell transplantation. In this study we evaluated the significance of lymphocyte recovery in 125 consecutive patients with hematologic malignancies who underwent double-unit CBT (DUCBT) with an anti-thymocyte globulin-containing regimen at our institution. A subset of 65 patients were prospectively evaluated for recovery of T, natural killer (NK) and B cells and in 46 patients we also examined viral-specific T cell recovery against Adenovirus, Epstein-Barr virus, cytomegalovirus, BK virus, respiratory syncytial virus and Influenza antigen. Our results indicate that in recipients of DUCBT, the day 30 absolute lymphocyte count is highly predictive of non-relapse mortality (NRM) and overall survival (OS). Immune recovery post-DUCBT was characterized by prolonged CD8+ and CD4+ T lymphopenia associated with preferential expansion of B and NK cells. We also observed profound delays in quantitative and functional recovery of viral-specific CD4+ and CD8+ T-cell responses for the first year post-CBT. Taken together, our data support efforts aimed at optimizing viral-specific T cell recovery to improve outcomes post-CBT. PMID:25708219

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

PubMed Central

Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

2016-01-01

Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

Plasma fractionation issues.

PubMed

Farrugia, Albert; Evers, Theo; Falcou, Pierre-Francois; Burnouf, Thierry; Amorim, Luiz; Thomas, Sylvia

2009-04-01

Procurement and processing of human plasma for fractionation of therapeutic proteins or biological medicines used in clinical practice is a multi-billion dollar international trade. Together the private sector and public sector (non-profit) provide large amounts of safe and effective therapeutic plasma proteins needed worldwide. The principal therapeutic proteins produced by the dichotomous industry include gamma globulins or immunoglobulins (including pathogen-specific hyperimmune globulins, such as hepatitis B immune globulins) albumin, factor VIII and Factor IX concentrates. Viral inactivation, principally by solvent detergent and other processes, has proven highly effective in preventing transmission of enveloped viruses, viz. HBV, HIV, and HCV.

Circadian variation in serum cortisol during hydrocortisone replacement is not attributable to changes in cortisol-binding globulin concentrations.

PubMed

Chung, T T; Gunganah, K; Monson, J P; Drake, W M

2016-04-01

Patients taking hydrocortisone (HC) replacement for primary or secondary adrenal failure require individual adjustment of their dose. In addition to modifying the administered doses of HC for each patient, physicians are increasingly interested in variations in the bioavailability of glucocorticoid replacement. One potential determinant of the bioavailability of replaced HC is a variation in serum cortisol-binding globulin (CBG) concentration, which may, in turn, affect interpretation of cortisol profiles and individual dose selection for patients on hydrocortisone replacement therapy. To investigate the hypothesis that there is a circadian variation in CBG levels. A total of 34 male patients divided into 3 groups (10 patients with non-somatotroph structural pituitary disease on HC replacement, 11 patients with treated acromegaly on HC replacement and 13 patients with treated acromegaly not on HC replacement) and 10 healthy volunteers were included. Cortisol and CBG levels were measured at 6 time points (0800, 1100, 1300, 1500, 1700 and 1900). No significant circadian variation in CBG concentration was found in any of the 4 groups. Circadian variation in serum cortisol during hydrocortisone replacement is not attributable to changes in cortisol-binding globulin concentration. Changes in serum cortisol levels may thus be explained by other factors including 11 β-hydroxysteroid dehydrogenase type 1 activity or circadian changes in the binding properties of CBG. © 2015 John Wiley & Sons Ltd.

Cholestatic Liver Disease after Rituximab and Adalimumab and the Possible Role of Cross-Reacting Antibodies to Fab 2 Fragments

PubMed Central

Koetter, Ina; Schwab, Matthias; Fritz, Peter; Kimmel, Martin; Alscher, M. Dominik; Braun, Niko

2013-01-01

Background Millions of patients are treated with therapeutic monoclonal antibodies (Tmabs) for miscellaneous diseases. We investigated sera from six patients who received immune globulin, from one patient with refractory anti-neutrophil-cytoplasmic antibody (ANCA)-associated granulomatosis with polyangiitis (GPA) who developed two episodes of acute cholestatic liver disease, one after treatment with rituximab and a second after adalimumab and a healthy control group. Methods Three sera from the patient and six sera from patients who received immune globulin were analyzed for antibodies to rituximab and adalimumab by ELISA. Additionally, sera from the patients and from nine healthy blood donors were coated with the Fab fragment of an unrelated humanized monoclonal antibody, with human Fc proteins as well as a mouse IgG globulin. Results Viral serology for hepatitis A, B, C and autoantibodies specific for autoimmune liver disorders were negative. In all three sera from the patient antibodies to rituximab could be detected, but also antibodies to adalimumab were present even at time points when the patient had not yet received adalimumab, indicating cross reactivity between both substances. Testing against an unrelated human Fab fragment revealed positive results, indicating that the patient had antibodies against human Fab fragments in general. The Fc proteins were negative, and patients’ sera did also not react with mouse IgG globulins. Remarkably, 2 out of 5 patients which were treated with immune globulin had antibodies against human Fab fragments in general whereas in none of the samples from healthy controls antibodies to Fab fragment could be detected. Conclusion This is the first study demonstrating cholestatic liver disease induced by two different Tmabs. Cross - reacting antibodies to Fab2 fragments in general are probably involved. Further studies must show if these Fab2 antibodies in general are related with drug-induced side effects and accelerated drug

Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques

PubMed Central

Meyer, C; Walker, J; Dewane, J; Engelmann, F; Laub, W; Pillai, S; Thomas, Charles R; Messaoudi, I

2015-01-01

In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease. PMID:25902927

Immune status of free-ranging green turtles with fibropapillomatosis from Hawaii

USGS Publications Warehouse

Work, Thierry M.; Rameyer, Robert; Balazs, George H.; Cray, Carolyn; Chang, Sandra P.

2001-01-01

Cell-mediated and humoral immune status of free-ranging green turtles (Chelonia mydas) in Hawaii (USA) with and without fibropapillornatosis (FP) were assessed. Tumored and non-tumored turtles from Kaneohe Bay (KB) on the island of Oahu and from FP-free areas on the west (Kona/Kohala) coast of the island of Hawaii were sampled from April 1998 through February 1999. Turtles on Oahu were grouped (0-3) for severity of tumors with 0 for absence of tumors, 1 for light, 2 for moderate, and 3 for most severe. Turtles were weighed, straight carapace length measured and the regression slope of weight to straight carapace length compared between groups (KB0, KB1, KB2, KB3, Kona). Blood was assayed for differential white blood cell count, hematocrit, in vitro peripheral blood mononuclear cell (PBMC) proliferation in the presence of concanavalin A (ConA) and phytohaemagglutinin (PHA), and protein electrophoresis. On Oahu, heterophil/lymphocyte ratio increased while eosinophil/monocyte ratio decreased with increasing tumors score. Peripheral blood mononuclear cell proliferation indices for ConA and PHA were significantly lower for turtles with tumor scores 2 and 3. Tumor score 3 turtles (KB3) had significantly lower hematocrit, total protein, alpha 1, alpha 2, and gamma globulins than the other four groups. No significant differences in immune status were seen between non-tumored (or KB1) turtles from Oahu and Hawaii. There was no significant difference between groups in regression slopes of body condition to carapace length. We conclude that turtles with severe FP are imunosuppressed. Furthermore, the lack of significant difference in immune status between non-tumored (and KB1) turtles from Oahu and Kona/Kohala indicates that immunosuppression may not be a prerequisite for development of FP.

BINDING OF SOLUBLE IMMUNE COMPLEXES TO HUMAN LYMPHOBLASTOID CELLS

PubMed Central

Theofilopoulos, Argyrios N.; Dixon, Frank J.; Bokisch, Viktor A.

1974-01-01

In the present work we studied the expression of membrane-bound Ig (MBIg) as well as receptors for IgG Fc and complement on nine human lymphoblastoid cell lines. When MBIg and receptors for IgG Fc were compared, four categories of cell lines could be distinguished: (a) cell lines having both MBIg and receptors for IgG Fc, (b) cell lines having MBIg but lacking receptors for IgG Fc, (c) cell lines lacking MBIg but having receptors for IgG Fc, and (d) cell lines lacking both MBIg and receptors for IgG Fc. Two types of receptors for complement could be detected on the cell lines studied, one for C3-C3b and one for C3d. When sensitized red cells carrying C3b or C3d were used for rosette tests, three categories of cell lines could be distinguished: (a) cell lines having receptors for C3b and C3d, (b) cell lines having receptors only for C3d and (c) cell lines lacking both receptors. However, when a more sensitive immunofluorescent method was used instead of the rosette technique, it was found that cell lines unable to form rosettes with EAC1423bhu were able to bind soluble C3 or C3b which indicated the presence of these receptors on the cell surface. Inhibition experiments showed that receptors for C3-C3b and receptors for C3d are distinct and that receptors for C3-C3b and C3d are different from receptors for IgG Fc. A cell line (Raji) without MBIg but with receptors for IgG Fc, C3-C3b, and C3d was selected for use in studying the binding mechanism of soluble immune complexes to cell surface membrane. Aggregated human gamma globulin was used in place of immune complexes. Immune complexes containing complement bind to Raji cells only via receptors for complement, namely receptors for C3-C3b and C3d. Binding of immune complexes containing complement to cells is much greater than that of complexes without complement. Immune complexes bound to cells via receptors for complement can be partially released from the cell surface by addition of normal human serum as well as

78 FR 12763 - Pediatric Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-25

... [Immune Globulin Subcutaneous (Human), 20% Liquid], INOMAX (nitric oxide), INVEGA (paliperidone), KEDBUMIN... (moxifloxacin ophthalmic solution 0.5%), NATROBA (spinosad), NEXIUM (esomeprazole magnesium), NEXIUM IV...

Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

PubMed Central

Roider, Tobias; Katzfuß, Michael; Matos, Carina; Singer, Katrin; Renner, Kathrin; Oefner, Peter J.; Dettmer-Wilde, Katja; Herr, Wolfgang; Holler, Ernst; Kreutz, Marina; Peter, Katrin

2016-01-01

Antithymocyte globulin (ATG) is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon®) on human monocyte-derived dendritic cells (DC). ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86. ATG-DC showed an increase in IL-10 secretion but no IL-12 production. In line with this tolerogenic phenotype, ATG caused a significant induction of indoleamine 2,3-dioxygenase expression and a concomitant increase in levels of tryptophan metabolites in the supernatants of DC. Further, ATG-DC did not induce the proliferation of allogeneic T cells in a mixed lymphocyte reaction but actively suppressed the T cell proliferation induced by mature DC. These data suggest that besides its well-known effect on T cells, ATG modulates the phenotype of DC in a tolerogenic way, which might constitute an essential part of its immunosuppressive action in vivo. PMID:27973435

Heat-Induced Soluble Protein Aggregates from Mixed Pea Globulins and β-Lactoglobulin.

PubMed

Chihi, Mohamed-Lazhar; Mession, Jean-luc; Sok, Nicolas; Saurel, Rémi

2016-04-06

The present work investigates the formation of protein aggregates (85 °C, 60 min incubation) upon heat treatment of β-lactoglobulin (βlg)-pea globulins (Glob) mixtures at pH 7.2 and 5 mM NaCl from laboratory-prepared protein isolates. Various βlg/Glob weight ratios were applied, for a total protein concentration of 2 wt % in admixture. Different analytical methods were used to determine the aggregation behavior of "mixed" aggregates, that is, surface hydrophobicity and also sulfhydryl content, protein interactions by means of SDS-PAGE electrophoresis, and molecule size distribution by DLS and gel filtration. The production of "mixed" thermal aggregates would involve both the formation of new disulfide bonds and noncovalent interactions between the denatured βlg and Glob subunits. The majority of "mixed" soluble aggregates displayed higher molecular weight and smaller diameter than those for Glob heated in isolation. The development of pea-whey protein "mixed" aggregates may help to design new ingredients for the control of innovative food textures.

Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP).

PubMed

Watson, J C; Hadler, S C; Dykewicz, C A; Reef, S; Phillips, L

1998-05-22

These revised recommendations of the Advisory Committee on Immunization Practices (ACIP) on measles, mumps, and rubella prevention supersede recommendations published in 1989 and 1990. This statement summarizes the goals and current strategies for measles, rubella, and congenital rubella syndrome (CRS) elimination and for mumps reduction in the United States. Changes from previous recommendations include: Emphasis on the use of combined MMR vaccine for most indications; A change in the recommended age for routine vaccination to 12-15 months for the first dose of MMR, and to 4-6 years for the second dose of MMR; A recommendation that all states take immediate steps to implement a two dose MMR requirement for school entry and any additional measures needed to ensure that all school-aged children are vaccinated with two doses of MMR by 2001; A clarification of the role of serologic screening to determine immunity; A change in the criteria for determining acceptable evidence of rubella immunity; A recommendation that all persons who work in health-care facilities have acceptable evidence of measles and rubella immunity; Changes in the recommended interval between administration of immune globulin and measles vaccination; and Updated information on adverse events and contraindications, particularly for persons with severe HIV infection, persons with a history of egg allergy or gelatin allergy, persons with a history of thrombocytopenia, and persons receiving steroid therapy.

Infant botulism type Ba: first culture-confirmed case in the United Arab Emirates.

PubMed

Fathalla, Waseem M; Mohammed, Khalid A; Ahmed, Elamin

2008-09-01

We report on a 3-month-old girl with culture-confirmed infant botulism caused by a rare double toxin-producing Clostridium botulinum type Ba. This case was not related to honey-feeding. The clinical course was prolonged, with minimal spontaneous improvement at onset, and a period of fluctuating motor weakness and nasogastric feeding dependence afterward. Neurophysiologic studies produced normal results. Human botulism immune globulin was administered empirically on day 23 of presentation, with rapid full recovery. This case highlights the importance of pursuing diagnoses of infant botulism despite normal results of neurophysiologic testing and no history of honey-feeding. Our case also demonstrates a favorable response to human botulism immune globulin, despite the relatively late treatment.

Specific labeling of the thyroxine binding site in thyroxine-binding globulin: determination of the amino acid composition of a labeled peptide fragment isolated from a proteolytic digest of the derivatized protein.

PubMed

Tabachnick, M; Perret, V

1987-08-01

[125I] Thyroxine has been covalently bound to the thyroxine binding site in thyroxine-binding globulin by reaction with the bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene. An average of 0.47 mol of [125I] thyroxine was incorporated per mol protein; nonspecific binding amounted to 8%. A labeled peptide fragment was isolated from a proteolytic digest of the derivatized protein by HPLC and its amino acid composition was determined. Comparison with the amino acid sequence of thyroxine-binding globulin indicated partial correspondence of the labeled peptide with two possible regions in the protein. These regions also coincide with part of the barrel structure present in the closely homologous protein, alpha 1-antitrypsin.

Expression of corticosteroid binding globulin in the rat olfactory system.

PubMed

Dölz, Wilfried; Eitner, Annett; Caldwell, Jack D; Jirikowski, Gustav F

2013-05-01

Glucocorticoids are known to act on the olfactory system although their mode of action is still unclear since nuclear glucocorticoid receptors are mostly absent in the olfactory mucosa. In this study we used immunocytochemistry, in situ hybridization, and RT-PCR to study the expression and distribution of corticosteroid binding globulin (CBG) in the rat olfactory system. Mucosal goblet cells could be immunostained for CBG. Nasal secretion contained measurable amounts of CBG suggesting that CBG is liberated. CBG immunoreactivity was localized in many of the basal cells of the olfactory mucosa, while mature sensory cells contained CBG only in processes as determined by double immunostaining with the olfactory marker protein OMP. This staining was most pronounced in the vomeronasal organ (VNO). The appearance of CBG in the non-sensory and sensory parts of the VNO and in nerve terminals in the accessory bulb indicated axonal transport. Portions of the periglomerular cells, the mitral cells and the tufted cells were also CBG positive. CBG encoding transcripts were confirmed by RT-PCR in homogenates of the olfactory mucosa and VNO. Olfactory CBG may be significant for uptake, accumulation and transport of glucocorticoids, including aerosolic cortisol. Copyright © 2012 Elsevier GmbH. All rights reserved.

Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis.

PubMed

Deswal, Ritu; Yadav, Arun; Dang, Amita Suneja

2018-02-01

Sex hormone-binding globulin (SHBG) is a glycoprotein which regulates bioavailability of sex steroid hormones. Interest in SHBG has escalated in recent years because of its inverse association with polycystic ovary syndrome (PCOS), obesity, insulin resistance, metabolic syndrome, and diabetes type II. This meta-analysis was performed to examine the associations of SHBG with PCOS and to correlate serum SHBG levels with various PCOS associated endocrine and metabolic dysregulation as well as to determine the effects of various therapeutic agents on serum SHBG levels in PCOS patients in order to assess the true accuracy of SHBG in the prediction of PCOS. A literature search was performed using Pub-Med, Science direct, google scholar, EMBASE, and Cochrane library. A total of 675 relevant records were identified, of which 62 articles were included. Meta-analysis using a random-effects model was performed using STATA version 13 to calculate standardized mean difference (SMD) with 95% confidence intervals (95 % CIs). SHBG levels in controls were significantly higher than that of PCOS patients (SMD= -0.83, 95%CI = -1.01, -0.64), with significant heterogeneity across studies (I 2 = 93.9% and p=0.000). Our results suggest that the lower serum SHBG levels are associated with the risk of PCOS. SHBG may also play an important role in various metabolic disturbances in PCOS patients. Therapeutic interventions improved SHBG levels in PCOS women which further reduced PCOS associated complications. Therefore, SHBG levels may prove to be a useful biomarker for the diagnosis and treatment of PCOS. Systematic review registration: PROSPERO CRD42017057972 Abbreviations: PCOS: polycystic ovary syndrome; SHBG: sex hormone-binding globulin.

21 CFR 610.21 - Limits of potency.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Diphtheria Antitoxin, 500 units per milliliter. Tetanus Antitoxin, 400 units per milliliter. Tetanus Immune Globulin (Human), 250 units of tetanus antitoxin per container. Antigens Cholera Vaccine, 8 units each of...

21 CFR 610.21 - Limits of potency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Diphtheria Antitoxin, 500 units per milliliter. Tetanus Antitoxin, 400 units per milliliter. Tetanus Immune Globulin (Human), 250 units of tetanus antitoxin per container. Antigens Cholera Vaccine, 8 units each of...

21 CFR 610.21 - Limits of potency.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Diphtheria Antitoxin, 500 units per milliliter. Tetanus Antitoxin, 400 units per milliliter. Tetanus Immune Globulin (Human), 250 units of tetanus antitoxin per container. Antigens Cholera Vaccine, 8 units each of...

21 CFR 610.21 - Limits of potency.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Diphtheria Antitoxin, 500 units per milliliter. Tetanus Antitoxin, 400 units per milliliter. Tetanus Immune Globulin (Human), 250 units of tetanus antitoxin per container. Antigens Cholera Vaccine, 8 units each of...

21 CFR 610.21 - Limits of potency.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Diphtheria Antitoxin, 500 units per milliliter. Tetanus Antitoxin, 400 units per milliliter. Tetanus Immune Globulin (Human), 250 units of tetanus antitoxin per container. Antigens Cholera Vaccine, 8 units each of...

Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses

PubMed Central

Vora, Kalpit A; Porter, Gene; Peng, Roche; Cui, Yan; Pryor, Kellyann; Eiermann, George; Zaller, Dennis M

2009-01-01

Background Current literature suggests that dipeptidyl peptidase IV (DPP-IV; CD26) plays an essential role in T-dependent immune responses, a role that could have important clinical consequences. To rigorously define the role of DPP-IV in the immune system, we evaluated genetic and pharmacological inhibition of the enzyme on T-dependent immune responses in vivo. Results The DPP-IV null animals mounted robust primary and secondary antibody responses to the T dependent antigens, 4-hydroxy-3-nitrophenylacetyl-ovalbumin (NP-Ova) and 4-hydroxy-3-nitrophenylacetyl-chicken gamma globulin (NP-CGG), which were comparable to wild type mice. Serum levels of antigen specific IgM, IgG1, IgG2a, IgG2b and IgG3 were similar between the two groups of animals. DPP-IV null animals mounted an efficient germinal center reaction by day 10 after antigen stimulation that was comparable to wild type mice. Moreover, the antibodies produced by DPP-IV null animals after repeated antigenic challenge were affinity matured. Similar observations were made using wild type animals treated with a highly selective DPP-IV inhibitor during the entire course of the experiments. T cell recall responses to ovalbumin and MOG peptide, evaluated by measuring proliferation and IL-2 release from cells isolated from draining lymph nodes, were equivalent in DPP-IV null and wild type animals. Furthermore, mice treated with DPP-IV inhibitor had intact T-cell recall responses to MOG peptide. In addition, female DPP-IV null and wild type mice treated with DPP-IV inhibitor exhibited normal and robust in vivo cytotoxic T cell responses after challenge with cells expressing the male H-Y minor histocompatibility antigen. Conclusion These data indicate Selective inhibition of DPP-IV does not impair T dependent immune responses to antigenic challenge. PMID:19358731

Corticosteroid-Binding Globulin: Structure-Function Implications from Species Differences

PubMed Central

Gardill, Bernd R.; Vogl, Michael R.; Lin, Hai-Yan; Hammond, Geoffrey L.; Muller, Yves A.

2012-01-01

Corticosteroid-binding globulin (CBG) transports glucocorticoids and progesterone in the blood and thereby modulates the tissue availability of these hormones. As a member of the serine protease inhibitor (SERPIN) family, CBG displays a reactive center loop (RCL) that is targeted by proteinases. Cleavage of the RCL is thought to trigger a SERPIN-typical stressed-to-relaxed (S-to-R) transition that leads to marked structural rearrangements and a reduced steroid-binding affinity. To characterize structure-function relationships in CBG we studied various conformational states of E. coli-produced rat and human CBG. In the 2.5 Å crystal structure of human CBG in complex with progesterone, the RCL is cleaved at a novel site that differs from the known human neutrophil elastase recognition site. Although the cleaved RCL segment is five residues longer than anticipated, it becomes an integral part of β-sheet A as a result of the S-to-R transition. The atomic interactions observed between progesterone and CBG explain the lower affinity of progesterone in comparison to corticosteroids. Surprisingly, CD measurements in combination with thermal unfolding experiments show that rat CBG fails to undergo an S-to-R transition upon proteolytic cleavage of the RCL hinting that the S-to-R transition observed in human CBG is not a prerequisite for CBG function in rat. This observation cautions against drawing general conclusions about molecular mechanisms by comparing and merging structural data from different species. PMID:23300763

Effect of Dietary Combination of Methionine and Fish Oil on Cellular Immunity and Plasma Fatty Acids in Infectious Bursal Disease Challenged Chickens

PubMed Central

Kasim, Azhar; Yong Meng, Goh; Teck Chwen, Loh; Kamalidehghan, Behnam; Soleimani Farjam, Abdoreza

2013-01-01

This study was carried out to investigate the modulatory effects of dietary methionine and fish oil on immune response, plasma fatty acid profile, and blood parameters of infectious bursal disease (IBD) challenged broiler chickens. A total of 300 one-day-old male broiler chicks were assigned to one of six dietary treatment groups in a 3 × 2 factorial arrangement. There were three levels of fish oil (0, 2.5 and 5.5%), and two levels of methionine (NRC recommendation and twice NRC recommendation). The results showed that the birds fed with 5.5% fish oil had higher total protein, white blood cell count, and IL-2 concentration than those of other groups at 7 days after IBD challenge. Inclusion of fish oil in diet had no effect on IFN-γ concentration. However, supplementation of methionine twice the recommendation enhanced the serum IFN-γ and globulin concentration. Neither of fish oil nor methionine supplementation affected the liver enzymes concentration. It can be suggested that a balance of moderate level of fish oil (2.5%) and methionine level (twice NRC recommendation) might enhance immune response in IBD challenged broiler chickens. PMID:24198724

Pharmaceutical approval update.

PubMed

Gohil, Kunj

2014-11-01

Naltrexone/bupropion (Contrave) for weight management; pembrolizumab (Keytruda) for melanoma; dolutegravir/abacavir/lamivudine (Triumeq) for HIV-1; and immune globulin infusion 10% (human) with recombinant human hyaluronidase (Hyqvia) for primary immunodeficiency.

Respiratory syncytial virus (RSV)

MedlinePlus

RSV; Palivizumab; Respiratory syncytial virus immune globulin; Bronchiolitis - RSV ... Crowe JE. Respiratory syncytial virus. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ...

Fasting ameliorates metabolism, immunity, and oxidative stress in carbon tetrachloride-intoxicated rats.

PubMed

Sadek, Km; Saleh, Ea

2014-12-01

Fasting has been recently discovered to improve overall health, but its beneficial effects in the presence of hepatic insufficiency have not been proven. The influence of fasting on the metabolism, immunological aspects, and oxidative stress of 40 male carbon tetrachloride (CCl4)-intoxicated Wistar rats was investigated in the present study. The rats were divided into four groups, including a placebo group, CCl4-intoxicated rats, which were injected subcutaneously with 1.0 ml/kg of CCl4 solution, a fasting group, which was fasted 12 h/day for 30 days, and a fourth group, which was injected with CCl4 and fasted. The metabolism, immunity, and oxidative stress improved in CCl4-intoxicated rats fasted for 12 h/day for 30 days, as evidenced in significant increase (p < 0.05) in total protein, globulin, immunoglobulin M (IgM) and IgG levels, and total antioxidant capacity. In contrast, significant decrease (p < 0.05) in blood glucose, total cholesterol, low-density lipoprotein-cholesterol, alanine aminotransferase, C-reactive protein, and malondialdehyde levels were observed. Compared with CCl4-intoxicated rats, significant differences in the albumin, triacylglycerol, high-density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol, cardiovascular risk factor, calcium and magnesium levels were not detected. The results of the present study showed that fasting improved metabolism, immunity, and oxidative stress in CCl4-intoxicated rats. Thus, fasting during Ramadan is safe for patients with hepatic disorders, as the prophet Mohammed (S) said "Keep the fast, keep your health". © The Author(s) 2014.

United States Army Medical Materiel Development Activity - 1989

DTIC Science & Technology

1990-01-31

physicians to treat diseases such as Korean Hemorrhagic Fever and Lassa Fever. * J-5 Human Monoclonal Antibody is secreted by cultured hybridomas that were...volunteer studies involving a collaborative effort between WRAIR and the Swiss Serum and Vaccine Institute (SSVI). s Lassa Fever Immune Plasma is an...immune globulin used to treat Lassa fever infections. The collection of human immune plasma in Africa is an ongoing contract effort. USANRIID performs

Preparation of a Homologous (Human) Intravenous Botulinal Immune Globulin.

DTIC Science & Technology

1983-05-01

lipoprotein ( HDL ) per ml of plasma to ŗ.06 mg/ml for beta- lipoprotein (LDL). Triglyceride and cholesterol levels were intermediate within this...OF LIPOPROTEIN DURING FRACTIONATION "( HDL ) (LDL) Triglyceride Cholesterol cxLipoprotein 8 LipoproteinSample mg/ml mg/ml mg/mi m/ml IVBG-l.A:"Plasma...plasminogen, prekallikrein, triglycerides , cholesterol , alpha- lipoprotein , beta- lipoprotein , clotting factors, fibrinogen and complement

Opsonic and protective activity of immunoglobulin, modified immunoglobulin, and serum against neonatal Escherichia coli K1 infection.

PubMed

Bortolussi, R; Fischer, G W

1986-02-01

Because modified immune serum globulin (M-ISG) has been proposed for therapy in neonatal bacterial sepsis, we evaluated it in a suckling rat model of Escherichia coli K1 sepsis. We compared a M-ISG preparation (lot 2581), which was protective against group B streptococcal (GBS) sepsis, with other M-ISG, standard ISG preparations and with adult and cord serum. All immune serum preparations and sera demonstrated opsonic activity against E. coli K1 and were superior to saline in protecting against death due to E. coli K1 sepsis. Survival rates were higher for one M-ISG preparation (lot 2581) than for randomly selected standard immune serum globulin and cord sera but were similar to adult sera in these protection studies. Therapeutic and opsonic activity of standard immune serum globulin and M-ISG prepared from the same donors were similar, suggesting that the different processes used for their manufacture did not affect these activities. Because the M-ISG preparation studied showed protective activity to both GBS and E. coli K1, we studied it further by adsorbing the preparation with GBS and E. coli K1. Opsonic activity to E. coli K1 was removed by E. coli adsorption but not by adsorption with GBS, indicating that this activity was not due to a single cross-reacting antibody. Empirical therapy with M-ISG prescreened for opsonic activity to both E. coli K1 and GBS may be of clinical value. Trials appear warranted to study the pharmacology and efficacy of M-ISG in septic newborns.

Blood Transfusion

MedlinePlus

... cells) Plasma and cryoprecipitate Gamma globulin Albumin Blood Irradiation A rare but potentially life-threatening complication of ... who are considered to have impaired immune system. Irradiation prevents white cells from attacking. Red Cell Transfusion ...

Serum albumin and globulin analysis for hepatocellular carcinoma detection avoiding false-negative results from alpha-fetoprotein test negative subjects

NASA Astrophysics Data System (ADS)

Wang, Jing; Feng, Shangyuan; Lin, Juqiang; Zeng, Yongyi; Li, Ling; Huang, Zufang; Li, Buhong; Zeng, Haishan; Chen, Rong

2013-11-01

Surface-enhanced Raman spectroscopy (SERS) of serum albumin and globulin were employed to detect hepatocellular carcinoma (HCC). Tentative assignments of SERS bands show specific biomolecular changes associated with cancer development. These changes include a decrease in relative amounts of tryptophan, glutamine, glycine, and serine, indicating excessive consumption of amino acids for protein duplication. Principal component analysis was also introduced to analyze the obtained spectra, resulting in both diagnostic sensitivity and specificity of 100%. More importantly, it reveals that this method can detect HCC patients with alpha-fetoprotein negative test results, suggesting its great potential as a new alternative to detect HCC.

Vaccine-derived poliomyelitis 12 years after infection in Minnesota.

PubMed

DeVries, Aaron S; Harper, Jane; Murray, Andrew; Lexau, Catherine; Bahta, Lynn; Christensen, Jaime; Cebelinski, Elizabeth; Fuller, Susan; Kline, Susan; Wallace, Gregory S; Shaw, Jing H; Burns, Cara C; Lynfield, Ruth

2011-06-16

A 44-year-old woman with long-standing common variable immunodeficiency who was receiving intravenous immune globulin suddenly had paralysis of all four limbs and the respiratory muscles, resulting in death. Type 2 vaccine-derived poliovirus was isolated from stool. The viral capsid protein VP1 region had diverged from the vaccine strain at 12.3% of nucleotide positions, and the two attenuating substitutions had reverted to the wild-type sequence. Infection probably occurred 11.9 years earlier (95% confidence interval [CI], 10.9 to 13.2), when her child received the oral poliovirus vaccine. No secondary cases were identified among close contacts or 2038 screened health care workers. Patients with common variable immunodeficiency can be chronically infected with poliovirus, and poliomyelitis can develop despite treatment with intravenous immune globulin.

21 CFR 610.41 - Donor deferral.

Code of Federal Regulations, 2010 CFR

2010-04-01

... infection due to hepatitis B surface antigen (HBsAg) when previously tested under § 610.40(a), (b), and (e) subsequently may donate Source Plasma for use in the preparation of Hepatitis B Immune Globulin (Human...

Valganciclovir (VGCV) followed by cytomegalovirus (CMV) hyperimmune globulin compared to VGCV for 200 days in abdominal organ transplant recipients at high risk for CMV infection: A prospective, randomized pilot study.

PubMed

Fleming, James N; Taber, David J; Weimert, Nicole A; Nadig, Satish; McGillicuddy, John W; Bratton, Charles F; Baliga, Prabhakar K; Chavin, Kenneth D

2017-12-01

With the advent of effective antivirals against cytomegalovirus (CMV), use of CMV hyperimmune globulin (HIG) has decreased. Although antiviral prophylaxis in patients at high risk for CMV is effective, many patients still have late infection, never developing antibodies sufficient to achieve immunity. Utilizing a combination of antiviral and CMV HIG may allow patients to achieve immunity and decrease late CMV infections. This was a prospective randomized, open-label, pilot study comparing valganciclovir (VGCV) prophylaxis for 200 days vs VGCV for 100 days followed by CMV HIG in abdominal transplant recipients at high risk for CMV. The primary outcome was a comparison of late CMV disease. Forty patients were randomized to VGCV for 200 days (n = 20) or VGCV for 100 days followed by 3 doses of monthly CMV HIG (n = 20). Numerically, more overall CMV infections occurred in the CMV HIG group (45 vs 20%, P = .09). No differences in overall CMV infections or late CMV disease were seen between groups (20% vs 15%, P = 1.00 and 0 vs 0, P = 1.00). All CMV disease occurred within 200 days, with 63% occurring while patients were on VGCV. No differences were found in toxicities, graft function, or rejection between groups. Patients with CMV infection at any time had a higher body weight than those who did not have an infection (82 vs 95 kg, P = .049). Use of CMV HIG sequentially with prophylaxis may be an effective and affordable prophylactic regimen in abdominal transplant recipients at high risk for CMV, and warrants larger prospective study. Increased monitoring for patients with obesity may be warranted. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Thymic function, anti-thymocytes globulins, and cancer after renal transplantation.

PubMed

Ducloux, Didier; Bamoulid, Jamal; Courivaud, Cécile; Gaugler, Béatrice; Rebibou, Jean-Michel; Ferrand, Christophe; Chalopin, Jean-Marc; Borg, Christophe; Tiberghien, Pierre; Saas, Philippe

2011-07-01

Prolonged CD4 T cell lymphopenia after polyclonal antithymocyte globulins (ATG) is associated with an increased rate of cancers. Here, we examined whether pre-transplant thymic function estimated by TREC levels is predictive of cancer occurrence following ATG treatment. The impact of TREC on cancer occurrence was analyzed in 115 consecutive incident renal transplant recipients having received ATG. Mean follow-up was 7.5±2.6years. After ATG induction, patients with the lowest pre-transplant TREC values had lower post-transplant CD4(+) and CD4(+) CD45RA(+) CD45RO(-) T cell counts, and a higher frequency of T cells with a regulatory phenotype (CD127(+)CD4(+)CD25(+)Foxp3(+)). Log-transformed pre-transplant TREC values were significantly lower in patients who developed cancer after transplantation (p<0.0001). The cumulative incidence of cancer was higher in patients having the lowest pre-transplant TREC values (T1 [low]: 47.4%, T2 [medium]: 12.5%, and T3 [high]: 2.7%; p<0.0001). In multivariate analysis, pre-transplant TREC value was the only predictive factor of cancer (HR, 0.39; 95% CI, 0.16 to 0.97, for one log (TREC/10(6) PBMC); p=0.046). Pre-transplant thymic function is associated with an increased rate of post-transplant cancer in patients having received ATG. Omitting ATG in recipients with low pre-transplant TREC values should be considered. Copyright © 2011 Elsevier B.V. All rights reserved.

Immune response

MedlinePlus

Innate immunity; Humoral immunity; Cellular immunity; Immunity; Inflammatory response; Acquired (adaptive) immunity ... normal and usually does not react against them. INNATE IMMUNITY Innate, or nonspecific, immunity is the defense ...

T-cell-replete haploidentical HSCT with low-dose anti-T-lymphocyte globulin compared with matched sibling HSCT and unrelated HSCT.

PubMed

Luo, Yi; Xiao, Haowen; Lai, Xiaoyu; Shi, Jimin; Tan, Yamin; He, Jingsong; Xie, Wanzhuo; Zheng, Weiyan; Zhu, Yuanyuan; Ye, Xiujin; Yu, Xiaohong; Cai, Zhen; Lin, Maofang; Huang, He

2014-10-23

We developed an approach of T-cell-replete haploidentical hematopoietic stem cell transplantation (HSCT) with low-dose anti-T-lymphocyte globulin and prospectively compared outcomes of all contemporaneous T-cell-replete HSCT performed at our center using matched sibling donors (MSDs), unrelated donors (URDs), and haploidentical related donors (HRDs). From 2008 to 2013, 90 patients underwent MSD-HSCT, 116 underwent URD-HSCT, and 99 underwent HRD-HSCT. HRDs were associated with higher incidences of grades 2 to 4 (42.4%) and severe acute graft-versus-host disease (17.2%) and nonrelapse mortality (30.5%), compared with MSDs (15.6%, 5.6%, and 4.7%, respectively; P < .05), but were similar to URDs, even fully 10/10 HLA-matched URDs. For high-risk patients, a superior graft-versus-leukemia effect was observed in HRD-HSCT, with 5-year relapse rates of 15.4% in HRD-HSCT, 28.2% in URD-HSCT (P = .07), and 49.9% in MSD-HSCT (P = .002). Furthermore, 5-year disease-free survival rates were not significantly different for patients undergoing transplantation using 3 types of donors, with 63.6%, 58.4%, and 58.3% for MSD, URD, and HRD transplantation, respectively (P = .574). Our data indicate that outcomes after HSCT from suitably matched URDs and HRDs with low-dose anti-T-lymphocyte globulin are similar and that HRD improves outcomes of patients with high-risk leukemia. This trial was registered at www.chictr.org (Chinese Clinical Trial Registry) as #ChiCTR-OCH-12002490. © 2014 by The American Society of Hematology.

Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG).

PubMed

Schöttner, M; Gansser, D; Spiteller, G

1997-12-01

Polar extracts of the stinging nettle (Urtica dioica L.) roots contain the ligans (+)-neoolivil, (-)-secoisolariciresinol, dehydrodiconiferyl alcohol, isolariciresinol, pinoresinol, and 3,4-divanillyltetrahydrofuran. These compounds were either isolated from Urtica roots, or obtained semisynthetically. Their affinity to human sex hormone binding globulin (SHBG) was tested in an in vitro assay. In addition, the main intestinal transformation products of plant lignans in humans, enterodiol and enterolactone, together with enterofuran were checked for their activity. All lignans except (-)-pinoresinol developed a binding affinity to SHBG in the in vitro assay. The affinity of (-)-3,4-divanillyltetrahydrofuran was outstandingly high. These findings are discussed with respect to potential beneficial effects of plant lignans on benign prostatic hyperplasia (BPH).

Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

PubMed Central

Herbert, Martha

2017-01-01

Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH) receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw) and modified (cooked and roasted) foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease. PMID:28894619

Testicular defense systems: immune privilege and innate immunity

PubMed Central

Zhao, Shutao; Zhu, Weiwei; Xue, Shepu; Han, Daishu

2014-01-01

The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. Testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. The breakdown of local testicular immune homeostasis may lead to orchitis, an etiological factor of male infertility. The mechanisms underlying testicular immune privilege have been investigated for a long time. Increasing evidence shows that both a local immunosuppressive milieu and systemic immune tolerance are involved in maintaining testicular immune privilege status. The mechanisms underlying testicular innate immunity are emerging based on the investigation of the pattern recognition receptor-mediated innate immune response in testicular cells. This review summarizes our current understanding of testicular defense mechanisms and identifies topics that merit further investigation. PMID:24954222

Influence of extremely low frequency electromagnetic fields on growth performance, innate immune response, biochemical parameters and disease resistance in rainbow trout, Oncorhynchus mykiss.

PubMed

Nofouzi, Katayoon; Sheikhzadeh, Najmeh; Mohamad-Zadeh Jassur, Davood; Ashrafi-Helan, Javad

2015-06-01

The effects of extremely low frequency electromagnetic fields on rainbow trout growth performance, innate immunity and biochemical parameters were studied. Rainbow trout (17-18 g) were exposed to electromagnetic fields (15 Hz) at 0.01, 0.1, 0.5, 5 and 50 µT, for 1 h daily over period of 60 days. Growth performance of fish improved in different treatment groups, especially at 0.1, 0.5, 5 and 50 µT. Immunological parameters, specifically hemagglutinating titer, total antiprotease and α1-antiprotease levels in treatment groups, were also enhanced. Total protein and globulin contents in the serum of fish exposed to 0.1, 0.5, 5 and 50 µT were significantly higher than those in the control group. No significant differences were found in serum enzyme activities, namely aspartate aminotransferase and alanine aminotransferase of fish in all treatment groups. Conversely, alkaline phosphatase level decreased in fish exposed to 0.01 and 50 µT electromagnetic fields. Meanwhile, electromagnetic induction at 0.1, 0.5, 5 and 50 µT enhanced fish protection against Yersinia ruckeri. These results indicated that these specific electromagnetic fields had possible effects on growth performance, nonspecific immunity and disease resistance of rainbow trout.

APRIL:TACI axis is dispensable for the immune response to rabies vaccination.

PubMed

Haley, Shannon L; Tzvetkov, Evgeni P; Lytle, Andrew G; Alugupalli, Kishore R; Plummer, Joseph R; McGettigan, James P

2017-08-01

There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell maturation antigen (BCMA)-expressed by B cells in various stages of maturation-with high affinity. We discovered that RABV-infected primary murine B cells upregulate APRIL ex vivo. Cytokines present at the time of antigen exposure affect the outcome of vaccination by influencing T and B cell activation and GC formation. Therefore, we hypothesized that the presence of APRIL at the time of RABV-based vaccine antigen exposure would support the generation of protective antibodies against RABV glycoprotein (G). In an effort to improve the response to RABV vaccination, we constructed and characterized a live recombinant RABV-based vaccine vector which expresses murine APRIL (rRABV-APRIL). Immunogenicity testing in mice demonstrated that expressing APRIL from the RABV genome does not impact the primary antibody response against RABV G compared to RABV alone. In order to evaluate the necessity of APRIL for the response to rabies vaccination, we compared the responses of APRIL-deficient and wild-type mice to immunization with rRABV. APRIL deficiency does not affect the primary antibody response to vaccination. Furthermore, APRIL expression by the vaccine did not improve the generation of long-lived antibody-secreting plasma cells (PCs) as serum antibody levels were equivalent

Testosterone, sex hormone-binding globulin, calculated free testosterone, and oestradiol in male vegans and omnivores.

PubMed

Key, T J; Roe, L; Thorogood, M; Moore, J W; Clark, G M; Wang, D Y

1990-07-01

Total testosterone (T), total oestradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were measured in plasma samples from fifty-one male vegans and fifty-seven omnivores of similar age. Free T concentration was estimated by calculation. In comparison with the omnivores, the vegans had 7% higher total T (P = 0.250), 23% higher SHBG (P = 0.001), 3% lower free T (P = 0.580), and 11% higher E2 (P = 0.194). In a subset of eighteen vegans and twenty-two omnivores for whom 4 d diet records were available, there were statistically significant correlations between T and polyunsaturated fatty acids (r 0.37), SHBG and fat (r 0.43 for total fat, 0.46 for saturated fatty acids and 0.33 for polyunsaturated fatty acids), and SHBG and alcohol (r-0.39). It is concluded that a vegan diet causes a substantial increase in SHBG but has little effect on total or free T or on E2.

TERMINATION OF TOLERANCE TO HUMAN GAMMA GLOBULIN IN MICE BY ANTIGEN AND BACTERIAL LIPOPOLYSACCHARIDE (ENDOTOXIN)

PubMed Central

Chiller, Jacques M.; Weigle, William O.

1973-01-01

Bacterial lipopolysaccharides (endotoxin) allowed the circumvention of the thymus-derived (T) cell helper function otherwise required for the antibody response in mice to human gamma globulin (HGG). In an analogous fashion, the state of tolerance to HGG, existing at a time when bone marrow-derived (B) cells had lost their unresponsiveness, could be terminated by the injection of both immunogenic HGG and endotoxin, but by neither given alone. However, no effect on tolerance to HGG could be observed when this regimen was followed at a time when B cells were tolerant. After the spontaneous recovery from tolerance in B cells, it seemed that specific priming was occurring in that population. This phenomenon was observed either by the injection of endotoxin and HGG or by the adoptive transfer of cells into irradiated hosts. These data have been discussed in the light of potential autoimmune manifestations that could theoretically follow a simultaneous gram-negative bacterial infection along with a release of self-antigen. PMID:4120288

Fast-track surgery improves postoperative clinical recovery and cellular and humoral immunity after esophagectomy for esophageal cancer.

PubMed

Chen, Lantao; Sun, Lixin; Lang, Yaoguo; Wu, Jun; Yao, Lei; Ning, Jinfeng; Zhang, Jinfeng; Xu, Shidong

2016-07-11

Our aim was to investigate the influence of FTS on human cellular and humoral immunity using a randomized controlled clinical study in esophageal cancer patients. Between October 2013 and December 2014, 276 patients with esophageal cancer in our department were enrolled in the study. The patients were randomized into two groups: FTS pathway group and conventional pathway group. The postoperative hospital stay, hospitalization expenditure, and postoperative complications were recorded. The markers of inflammatory and immune function were measured before operation as well as on the 1st, 3rd, and 7th postoperative days (POD), including serum level of interleukin-6 (IL-6), C-reactive protein (CRP), serum globulin, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA) and lymphocyte subpopulations (CD3 lymphocytes, CD4 lymphocytes, CD8 lymphocytes and the CD4/CD8 ratio) in the patients between the two groups. In all, 260 patients completed the study: 128 in the FTS group and 132 in the conventional group. We found implementation of FTS pathway decreases postoperative length of stay and hospital charges (P < 0.05). In addition, inflammatory reactions, based on IL-6 and CRP levels, were less intense following FTS pathway compared to conventional pathway on POD1 and POD3 (P < 0.05). On POD1 and POD3, the levels of IgG, IgA, CD3 lymphocytes, CD4 lymphocytes and the CD4/CD8 ratio in FTS group were significantly higher than those in control group (All P < 0.05). However, there were no differences in the level of IgM and CD8 lymphocytes between the two groups. FTS improves postoperative clinical recovery and effectively inhibited release of inflammatory factors via the immune system after esophagectomy for esophageal cancer. ChiCTR-TRC-13003562 , the date of registration: August 29, 2013.

Grizzly bear corticosteroid binding globulin: Cloning and serum protein expression.

PubMed

Chow, Brian A; Hamilton, Jason; Alsop, Derek; Cattet, Marc R L; Stenhouse, Gordon; Vijayan, Mathilakath M

2010-06-01

Serum corticosteroid levels are routinely measured as markers of stress in wild animals. However, corticosteroid levels rise rapidly in response to the acute stress of capture and restraint for sampling, limiting its use as an indicator of chronic stress. We hypothesized that serum corticosteroid binding globulin (CBG), the primary transport protein for corticosteroids in circulation, may be a better marker of the stress status prior to capture in grizzly bears (Ursus arctos). To test this, a full-length CBG cDNA was cloned and sequenced from grizzly bear testis and polyclonal antibodies were generated for detection of this protein in bear sera. The deduced nucleotide and protein sequences were 1218 bp and 405 amino acids, respectively. Multiple sequence alignments showed that grizzly bear CBG (gbCBG) was 90% and 83% identical to the dog CBG nucleotide and amino acid sequences, respectively. The affinity purified rabbit gbCBG antiserum detected grizzly bear but not human CBG. There were no sex differences in serum total cortisol concentration, while CBG expression was significantly higher in adult females compared to males. Serum cortisol levels were significantly higher in bears captured by leg-hold snare compared to those captured by remote drug delivery from helicopter. However, serum CBG expression between these two groups did not differ significantly. Overall, serum CBG levels may be a better marker of chronic stress, especially because this protein is not modulated by the stress of capture and restraint in grizzly bears. Copyright 2010 Elsevier Inc. All rights reserved.

Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts.

PubMed

Gansser, D; Spiteller, G

1995-01-01

A test system is described, which allows the search for compounds interfering with human sex hormone-binding globulin (SHBG) even in complex plant extracts. The method has been evaluated and applied to Urtica dioica root extracts. The lignan secoisolariciresinol (5) as well as a mixture of isomeric (11 E)-9,10,13-trihydroxy-11-octadecenoic and (10 E)-9,12,13-trihydroxy-10-octadecenoic acids (3 and 4, resp.) were demonstrated to reduce binding activity of human SHBG. Methylation of the mixture of 3 and 4 increased its activity about 10-fold.

Immunological unresponsiveness in mice. II. Cellular basis of immunological unresponsiveness induced in foetal and neonatal mice by transfer of human gamma-globulin by the maternal route.

PubMed Central

Shinka, S; Komatsu, T; Dohi, Y; Amano, T

1979-01-01

The cellular basis of the mechanism of immunological tolerance to human gamma-globulin (H gamma G) induced in foetal and neonatal mice by materno-foetal or materno-neonatal transfer after a single injection of tolerogen (deaggregated H gamma G) into the mothers was investigated using a cell transfer system and assays of passive haemagglutinating antibodies and plaque-forming cells to H gamma G. The results demonstrated that B cells are mainly involved in the tolerance induced on the fourteenth day of gestation, whereas inactivation of T cells may account for the tolerance induced on the eighteenth day of gestation and in the neonatal stage. Treatment of the mothers with tolerogen and then anti-H gamma G serum reduced the tolerance induced on the fourteenth day of gestation, but did not affect that induced on the eighteenth day of gestation and in the neonatal stage. Cell transfer experiments showed that B-cell tolerance induced on the fourteenth day of gestation was prevented by passive antibody, while T-cell tolerance induced on the eighteenth day of gestation and in the neonatal stage was not affected by passive antibody. Assay of the anti-DNP antibody response after immunization with DNP10-H gamma G showed that treatment of mice with the tolerogen on the eighteenth day of gestation, but not the fourteenth day of gestation, inactivated H gamma G-reactive helper cells. The significance of these results is discussed in relation to the results of the cell transfer experiments described as above. PMID:89080

Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes

PubMed Central

Toor, Amir A.; Sabo, Roy T.; Roberts, Catherine H.; Moore, Bonny L.; Salman, Salman R.; Scalora, Allison F.; Aziz, May T.; Shubar Ali, Ali S.; Hall, Charles E.; Meier, Jeremy; Thorn, Radhika M.; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B.; McCarty, John M.; Chung, Harold M.; Manjili, Masoud H.; Neale, Michael C.

2016-01-01

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3+ cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3+ at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices

PubMed Central

Vellozzi, Claudia; Reingold, Arthur; Harris, Aaron; Haber, Penina; Ward, John W.; Nelson, Noele P.

2018-01-01

Summary Hepatitis B virus (HBV) is transmitted via blood or sexual contact. Persons with chronic HBV infection are at increased risk for cirrhosis and liver cancer and require medical care. This report updates and summarizes previously published recommendations from the Advisory Committee on Immunization Practices (ACIP) and CDC regarding the prevention of HBV infection in the United States. ACIP recommends testing all pregnant women for hepatitis B surface antigen (HBsAg), and testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA); administration of HepB vaccine and hepatitis B immune globulin (HBIG) for infants born to HBV-infected women within 12 hours of birth, followed by completion of the vaccine series and postvaccination serologic testing; universal hepatitis B vaccination within 24 hours of birth, followed by completion of the vaccine series; and vaccination of children and adolescents aged <19 years who have not been vaccinated previously. ACIP recommends vaccination of adults at risk for HBV infection, including universal vaccination of adults in settings in which a high proportion have risk factors for HBV infection and vaccination of adults requesting protection from HBV without acknowledgment of a specific risk factor. These recommendations also provide CDC guidance for postexposure prophylaxis following occupational and other exposures. This report also briefly summarizes previously published American Association for the Study of Liver Diseasest guidelines for maternal antiviral therapy to reduce perinatal HBV transmission. PMID:29939980

Hepatitis A Test

MedlinePlus

... of immune globulin instead of the vaccine for post-exposure protection. Although hepatitis A IgM antibodies are considered diagnostic for acute infection with hepatitis A, there has been increasing use of the test in people who do not have signs and ...

Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae.

PubMed

Nguyen, Ut V; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Van Poucke, Mario; Peelman, Luc; Goddeeris, Bruno M; Cox, Eric

2015-06-23

F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA(+) B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA(+) B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity.

U.S. Immunization program adult immunization activities and resources.

PubMed

Woods, LaDora O; Bridges, Carolyn B; Graitcer, Samuel B; Lamont, Brock

2016-04-02

Adults are recommended to receive vaccines based on their age, medical conditions, prior vaccinations, occupation and lifestyle. However, adult immunization coverage is low in the United States and lags substantially below Healthy People 2020 goals. To assess activities and resources designated for adult immunization programs by state and local health department immunization programs in the United States, we analyzed 2012 and 2013 data from the Centers for Disease Control and Prevention's (CDC) Program Annual Reports and Progress Assessments (PAPA) survey of CDC-funded immunization programs. Fifty-six of 64 funded US immunization programs' responses were included in the analysis. Eighty-two percent of (n = 46) programs reported having a designated adult immunization coordinator in 2012 and 73% (n = 41) in 2013. Of the 46 coordinators reported in 2012, 30% (n = 14) spent more than 50% of their time on adult immunization activities, and only 24% (n = 10) of the 41 adult coordinators in 2013 spent more than 50% of their time on adult immunization activities. In 2012, 23% (n = 13) of the 56 programs had a separate immunization coalition for adults and 68% (n = 38) included adult issues in their overall immunization program coalition. In 2013, 25% (n = 14) had a separate adult immunization coalition while 57% (n = 32) incorporated adult immunizations into their overall immunization program coalition. The results indicate substantial variation across the US in public health infrastructure to support adult immunizations. Continued assessment of adult immunization resources and activities will be important in improving adult immunization coverage levels though program support. With many programs having limited resources dedicated to improving adult immunization rates in the in US, efforts by the health departments to collaborate with providers and other partners in their jurisdictions to increase awareness, increase the use of proven strategies to improve vaccination of

U.S. Immunization program adult immunization activities and resources

PubMed Central

Woods, LaDora O.; Bridges, Carolyn B.; Graitcer, Samuel B.; Lamont, Brock

2016-01-01

ABSTRACT Adults are recommended to receive vaccines based on their age, medical conditions, prior vaccinations, occupation and lifestyle. However, adult immunization coverage is low in the United States and lags substantially below Healthy People 2020 goals. To assess activities and resources designated for adult immunization programs by state and local health department immunization programs in the United States, we analyzed 2012 and 2013 data from the Centers for Disease Control and Prevention's (CDC) Program Annual Reports and Progress Assessments (PAPA) survey of CDC-funded immunization programs. Fifty-six of 64 funded US immunization programs' responses were included in the analysis. Eighty-two percent of (n = 46) programs reported having a designated adult immunization coordinator in 2012 and 73% (n = 41) in 2013. Of the 46 coordinators reported in 2012, 30% (n = 14) spent more than 50% of their time on adult immunization activities, and only 24% (n = 10) of the 41 adult coordinators in 2013 spent more than 50% of their time on adult immunization activities. In 2012, 23% (n = 13) of the 56 programs had a separate immunization coalition for adults and 68% (n = 38) included adult issues in their overall immunization program coalition. In 2013, 25% (n = 14) had a separate adult immunization coalition while 57% (n = 32) incorporated adult immunizations into their overall immunization program coalition. The results indicate substantial variation across the US in public health infrastructure to support adult immunizations. Continued assessment of adult immunization resources and activities will be important in improving adult immunization coverage levels though program support. With many programs having limited resources dedicated to improving adult immunization rates in the in US, efforts by the health departments to collaborate with providers and other partners in their jurisdictions to increase awareness, increase the use of proven strategies to improve

Seasonal trends in nesting leatherback turtle (Dermochelys coriacea) serum proteins further verify capital breeding hypothesis

PubMed Central

Perrault, Justin R.; Wyneken, Jeanette; Page-Karjian, Annie; Merrill, Anita; Miller, Debra L.

2014-01-01

Serum protein concentrations provide insight into the nutritional and immune status of organisms. It has been suggested that some marine turtles are capital breeders that fast during the nesting season. In this study, we documented serum proteins in neophyte and remigrant nesting leatherback sea turtles (Dermochelys coriacea). This allowed us to establish trends across the nesting season to determine whether these physiological parameters indicate if leatherbacks forage or fast while on nesting grounds. Using the biuret method and agarose gel electrophoresis, total serum protein (median = 5.0 g/dl) and protein fractions were quantified and include pre-albumin (median = 0.0 g/dl), albumin (median = 1.81 g/dl), α1-globulin (median = 0.90 g/dl), α2-globulin (median = 0.74 g/dl), total α-globulin (median = 1.64 g/dl), β-globulin (median = 0.56 g/dl), γ-globulin (median = 0.81 g/dl) and total globulin (median = 3.12 g/dl). The albumin:globulin ratio (median = 0.59) was also calculated. Confidence intervals (90%) were used to establish reference intervals. Total protein, albumin and total globulin concentrations declined in successive nesting events. Protein fractions declined at less significant rates or remained relatively constant during the nesting season. Here, we show that leatherbacks are most likely fasting during the nesting season. A minimal threshold of total serum protein concentrations of around 3.5–4.5 g/dl may physiologically signal the end of the season's nesting for individual leatherbacks. The results presented here lend further insight into the interaction between reproduction, fasting and energy reserves and will potentially improve the conservation and management of this imperiled species. PMID:27293623

Immunization Information System and Informatics to Promote Immunizations: Perspective From Minnesota Immunization Information Connection.

PubMed

Muscoplat, Miriam Halstead; Rajamani, Sripriya

2017-01-01

The vision for management of immunization information is availability of real-time consolidated data and services for all ages, to clinical, public health, and other stakeholders. This is being executed through Immunization Information Systems (IISs), which are population-based and confidential computerized systems present in most US states and territories. Immunization Information Systems offer many functionalities, such as immunization assessment reports, client follow-up, reminder/recall feature, vaccine management tools, state-supplied vaccine ordering, comprehensive immunization history, clinical decision support/vaccine forecasting and recommendations, data processing, and data exchange. This perspective article will present various informatics tools in an IIS, in the context of the Minnesota Immunization Information Connection.

How do plants achieve immunity? Defence without specialized immune cells.

PubMed

Spoel, Steven H; Dong, Xinnian

2012-01-25

Vertebrates have evolved a sophisticated adaptive immune system that relies on an almost infinite diversity of antigen receptors that are clonally expressed by specialized immune cells that roam the circulatory system. These immune cells provide vertebrates with extraordinary antigen-specific immune capacity and memory, while minimizing self-reactivity. Plants, however, lack specialized mobile immune cells. Instead, every plant cell is thought to be capable of launching an effective immune response. So how do plants achieve specific, self-tolerant immunity and establish immune memory? Recent developments point towards a multilayered plant innate immune system comprised of self-surveillance, systemic signalling and chromosomal changes that together establish effective immunity.

How safe is the use of chlorpyrifos: Revelations through its effect on layer birds.

PubMed

Singh, P P; Kumar, Ashok; Chauhan, R S; Pankaj, P K

2016-07-01

The present study was aimed to investigate the immunological competence of chlorpyrifos (CPF) insecticide after oral administration in layer chickens. A total of 20 White Leghorn birds were given CPF in drinking water at 0.3 ppm/bird/day (no observable effect level dose) for a period of 3-month. Immune competence status of layer birds and chicks hatched from CPF-treated birds were estimated at 15 days interval in layer birds and monthly interval in chicks using immunological and biochemical parameters. There was a significant decrease in values of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds treated with CPF as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with CPF as compared to control. Subsequently, chicks produced from CPF-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. The exposure to CPF produced hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting total stoppage of using CPF in poultry sheds.

Tetanus: Diagnosis and Treatment

MedlinePlus

... is a medical emergency requiring: Care in the hospital Immediate treatment with medicine called human tetanus immune globulin (TIG) Aggressive wound care Drugs to control muscle spasms Antibiotics Tetanus vaccination Depending on how serious the infection is, a machine to help you breathe may ...

Studies of the antibody nature of the rheumatoid factor

PubMed Central

Aho, K.; Harboe, M.; Leikola, J.

1964-01-01

The reaction of the rheumatoid factor (RF) with 7S γ-globulin antibodies of nine persons immunized with sheep erythrocytes was studied. All of a panel of rheumatoid sera with high Waaler-Rose titres agglutinated sheep cells sensitized with the human anti-sheep cell antibodies and O Rh positive cells sensitized with the `diagnostic' anti-CD serum Ripley. The RF measurable with these systems could be absorbed to diphtheria toxoid—human antitoxin precipitate, whereas the absorption with egg albumin—rabbit anti-egg albumin precipitate did not result in any appreciable titre reduction. However, the eluate from the rabbit precipitate was highly active in these systems, whereas Rh positive cells sensitized with anti-Rh sera suitable for Gm(a) typing were not regularly agglutinated. A markedly greater concentration of native than of heat-aggregated γ-globulin was needed for inhibition of the agglutination by the RF of cells heavily sensitized with the human anti-sheep cell antibodies. No appreciable difference in this respect was seen when using lightly sensitized cells. Only the heavily sensitized cells fixed complement. The `natural' 7S γ-globulin antibodies against sheep cells were neither suited for demonstration of RF nor did they fix complement. Sheep cells coated with 7S γ-globulin antibodies of a Gm(a+) person were agglutinated by a non-rheumatoid anti-Gm(a) serum, and this system was well suited for Gm(a) typing, whereas cells coated with antibodies of a Gm(a-) person were not agglutinated. Rheumatoid anti-Gm(a) sera agglutinated cells sensitized with antibodies of both Gm(a+) and Gm(a-) persons. Using cells coated with Gm(a+) antibodies, some distinction between Gm(a+) and Gm(a-) sera could be obtained under carefully controlled conditions. The use of a Gm(a-) coat resulted in a slight difference in the inhibiting capacity, which had no relation to the serum's Gm(a) type. The results suggest that the reaction of the RF with sheep cells heavily sensitized

Eosinophilic fasciitis

MedlinePlus

... include: CBC with differential Gamma globulins (a type of immune system protein) Erythrocyte sedimentation rate ( ESR ) MRI Muscle biopsy ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is ...

Purification and properties of squirrel monkey (Saimiri sciureus) corticosteroid binding globulins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhn, R.W.; Weber, C.V.; Siiteri, P.K.

1988-04-05

Corticosteroid binding globulin (CBG), a serum glycoprotein which binds glucocorticoids and progestins with high affinity, is widely distributed throughout the animal world. Although its charge and size characteristics have largely been conserved across species, the authors found the behavior of CBG in squirrel monkey (Saimiri sciureus) serum during fractionation by polyacrylamide gel electrophoresis or Sephadex chromatography was consistent with a molecule about twice the size of that found in most species. To more fully understand the basis for this difference, they purified the protein by sequential affinity and DEAE-Sepharose chromatographies. The final product was obtained in greater than 60% yieldmore » and was found to migrate as a single homogeneous band when examined by electrophoresis. The steroid binding specificity of the purified protein was identical with that of the protein in the starting serum. In contrast to the single protein band observed following electrophoresis under normal conditions, separations in the presence of sodium dodecyl sulfate (SDS) resolved the pure protein into two bands: one at 54,000 daltons and one at 57,000 daltons. Unlike other species, squirrel monkey CBG exists as a dimer in its native state. Antibodies were generated against the purified material and tested for cross-reactivity against the sera from other species by both radioimmunodiffusion and radioimmunoassay techniques. Only serum from titi monkeys was observed to cross-react when examined by radioimmunoassay. Taken together, the results suggest that New World monkey CBG's are distinct from those of other species in both size and immunologic characteristics.« less

Emerging Role of Corticosteroid-Binding Globulin in Glucocorticoid-Driven Metabolic Disorders.

PubMed

Moisan, Marie-Pierre; Castanon, Nathalie

2016-01-01

Glucocorticoid hormones (GCs) are critical for survival since they ensure the energy supply necessary to the body in an ever challenging environment. GCs are known to act on appetite, glucose metabolism, fatty acid metabolism, and storage. However, to be beneficial to the body, GC levels should be maintained in an optimal window of concentrations. Not surprisingly, conditions of GC excess or deficiency, e.g., Cushing's syndrome or Addison's disease, are associated with severe alterations of energy metabolism. Corticosteroid-binding globulin (CBG), through its high specific affinity for GCs, plays a critical role in regulating plasma GC levels and their access to target cells. Genetic studies in various species including humans have revealed that CBG is the major factor influencing interindividual genetic variability of plasma GC levels, both in basal and stress conditions. Some, but not all, of these genetic studies have also provided data linking CBG levels to body composition and insulin levels. The examination of CBG-deficient mice submitted to hyperlipidic diets unveiled specific roles for CBG in lipid storage and metabolism. An influence of CBG on appetite has not been reported but remains to be more finely analyzed. Finally, only male mice have been examined under high-fat diet, while obesity is affecting women even more than men. Overall, a role of CBG in GC-driven metabolic disorders is emerging in recent studies. Although subtle, the influence of CBG in these diseases could open the way to new therapeutic interventions since CBG is easily accessible in the blood.

Comparison of Serum Protein Electrophoresis Values in Wild and Captive Whooping Cranes ( Grus americana ).

PubMed

Hausmann, Jennifer C; Cray, Carolyn; Hartup, Barry K

2015-09-01

Protein electrophoresis of serum samples from endangered, wild whooping cranes ( Grus americana ) was performed to help assess the health of the only self-sustaining, migratory population in North America. Serum samples from wild adult cranes (n = 22) were taken at Aransas National Wildlife Refuge, Texas, USA during winter. Wild juvenile cranes (n = 26) were sampled at Wood Buffalo National Park, Northwest Territories, Canada, in midsummer. All captive crane samples were acquired from the International Crane Foundation, Baraboo, WI, USA. Captive adult cranes (n = 30) were sampled during annual examinations, and archived serum samples from captive juvenile cranes (n = 19) were selected to match the estimated age of wild juveniles. Wild juveniles had significantly lower concentrations of all protein fractions than wild adults, except for prealbumin and γ globulins. All protein fraction concentrations for wild juveniles were significantly lower compared with captive juveniles, except for prealbumin and γ globulins, which were higher. Wild adults had significantly greater γ globulin concentrations than captive adults. Captive juveniles had significantly lower prealbumin and albumin concentrations and albumin : globulin ratios than captive adults. The higher γ globulin concentrations in wild versus captive cranes are likely because of increased antigenic exposure and immune stimulation. Protein fraction concentrations vary significantly with age and natural history in this species. Reference intervals for serum protein electrophoresis results from captive adult whooping cranes are provided in this study.

Hepatitis A, B and nAnB: The Viruses and their Prevention

PubMed Central

Minuk, G. Y.

1985-01-01

Three viruses commonly infect the liver: hepatitis A virus (HAV), hepatitis B virus (HBV) and the virus(es) responsible for non A non B hepatitis (nAnB). HAV infection occurs predominantly by the fecal-oral route and thus is more common in areas where living conditions are poor and personal hygiene suboptimal. Immune serum globulin (ISG) prevents this form of hepatitis. HBV infection can be spread by either parenteral (e.g. drug abuse) or non-parenteral (e.g. intimate contact) routes. High risk, susceptible individuals should be vaccinated with the HBV vaccine for longterm protection. Hepatitis B immune globulin (HBIG) remains the treatment of choice after exposure, but its protective effect does not exceed three to four months. The nAnB agent is spread by the same routes as HBV infection. At present there is no convincing evidence that any form of active or passive prophylaxis is beneficial for this form of hepatitis. PMID:21279152

Improved serological response to human diploid cell rabies vaccine when given simultaneously with antirabies hyperimmune globulin.

PubMed

Navarrete-Navarro, S; Aguilar-Setién, A; Avila-Figueroa, C; Hernández-Sierra, F; Santos-Preciado, J I

1999-01-01

The prevention of rabies in Mexico continues to be an important goal for the health sector. Although the prevalence of this disease continues to fall, between 1990 and 1995 a total of 238 cases were registered (an average of 40 cases annually), with a mean annual incidence of 0.04 cases per 100,000 inhabitants and a mortality of almost 100%, so that it is important to rely on highly effective vaccines with few side effects. The objective of this work was to evaluate seroconversion and tolerance to the human diploid cell antirabies vaccine administered to individuals with a history of exposure to rabies, to compare these results with those reported in the literature for the Fuenzalida vaccine, a rabies vaccine produced in the brain tissue of suckling mice, and to find the role antirabies hyperimmune gamma globulin plays in the concentration of post-vaccination antibody concentrations. An analytical transverse study was carried out in 40 children and adults with a history of rabies exposure who were given a complete, five-dose intramuscular schedule of the human diploid cell rabies vaccine. Subjects were followed daily, and local and systemic signs and symptoms were recorded. Two blood samples (at baseline and at the end of the vaccination schedule) were taken and antibody titers against rabies glycoprotein, using the ELISA technique, were measured. Adverse side effects produced by the human diploid cell antirabies vaccine, such as frequency of pain, erythema, itching, and regional adenopathy were fewer than those reported in the literature for the Fuenzalida vaccine (p < 0.05), and of induration and local pain (p < 0.05) in relation to the latter vaccine. All patients seroconverted, producing geometric mean antibody titers of 6.22 IU/mL, an arithmetic mean titer of 9.66 IU/mL with a SD of 9.1 IU/mL. The level of tolerance to the diploid cell vaccine was good and its adverse effects were minimal and fewer than those reported for the Fuenzalida rabies vaccine

Impact of pharmacists providing immunizations on adolescent influenza immunization.

PubMed

Robison, Steve G

2016-01-01

To determine if the Oregon law change in 2011 to allow pharmacists to immunize adolescents 11 to 17 years of age increased influenza immunizations or changed existing immunization venues. With the use of Oregon's ALERT Immunization Information System (IIS), 2 measures of impact were developed. First, the change in adolescent age 11-17 influenza immunizations before (2007-2010) and after (2011-2014) the pharmacy law change was evaluated against a reference cohort (aged 7-10) not affected by the law. Community pharmacies were also compared with other types of influenza immunization sites within one of the study influenza seasons (2013-2014). From 2007 to 2014, adolescent influenza immunizations at community pharmacies increased from 36 to 6372 per year. After the 2011 pharmacy law change, adolescents aged 11 to 17 were more likely to receive an influenza immunization compared with the reference population (odds ratio, 1.21; 95% CI, 1.19-1.22). Analysis of the 2013-2014 influenza season suggests that community pharmacies immunized a different population of adolescents than other providers. The 2011 change in Oregon law allowed pharmacists to increase the total of influenza immunizations given to adolescents. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Potential effects of brevetoxins and toxic elements on various health variables in Kemp's ridley (Lepidochelys kempii) and green (Chelonia mydas) sea turtles after a red tide bloom event.

PubMed

Perrault, Justin R; Stacy, Nicole I; Lehner, Andreas F; Mott, Cody R; Hirsch, Sarah; Gorham, Jonathan C; Buchweitz, John P; Bresette, Michael J; Walsh, Catherine J

2017-12-15

Natural biotoxins and anthropogenic toxicants pose a significant risk to sea turtle health. Documented effects of contaminants include potential disease progression and adverse impacts on development, immune function, and survival in these imperiled species. The shallow seagrass habitats of Florida's northwest coast (Big Bend) serve as an important developmental habitat for Kemp's ridley (Lepidochelys kempii) and green (Chelonia mydas) sea turtles; however, few studies have been conducted in this area. Our objectives were (1) to evaluate plasma analytes (mass, minimum straight carapace length, body condition index [BCI], fibropapilloma tumor score, lysozyme, superoxide dismutase, reactive oxygen/nitrogen species, plasma protein electrophoresis, cholesterol, and total solids) in Kemp's ridleys and green turtles and their correlation to brevetoxins that were released from a red tide bloom event from July-October 2014 in the Gulf of Mexico near Florida's Big Bend, and (2) to analyze red blood cells in Kemp's ridleys and green turtles for toxic elements (arsenic, cadmium, lead, mercury, selenium, thallium) with correlation to the measured plasma analytes. Positive correlations were observed between brevetoxins and α 2 -globulins in Kemp's ridleys and α 2 - and γ-globulins in green turtles, indicating potential immunostimulation. Arsenic, cadmium, and lead positively correlated with superoxide dismutase in Kemp's ridleys, suggesting oxidative stress. Lead and mercury in green turtles negatively correlated with BCI, while mercury positively correlated with total tumor score of green turtles afflicted with fibropapillomatosis, suggesting a possible association with mercury and increased tumor growth. The total tumor score of green turtles positively correlated with total protein, total globulins, α 2 -globulins, and γ-globulins, further suggesting inflammation and immunomodulation as a result of fibropapillomatosis. Lastly, brevetoxin concentrations were positively

Integrated Immune

NASA Technical Reports Server (NTRS)

Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarnece

2010-01-01

This slide presentation reviews the program to replace several recent studies about astronaut immune systems with one comprehensive study that will include in-flight sampling. The study will address lack of in-flight data to determine the inflight status of immune systems, physiological stress, viral immunity, to determine the clinical risk related to immune dysregulation for exploration class spaceflight, and to determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

N-Glycans Modulate the Function of Human Corticosteroid-Binding Globulin*

PubMed Central

Sumer-Bayraktar, Zeynep; Kolarich, Daniel; Campbell, Matthew P.; Ali, Sinan; Packer, Nicolle H.; Thaysen-Andersen, Morten

2011-01-01

Human corticosteroid-binding globulin (CBG), a heavily glycosylated protein containing six N-linked glycosylation sites, transports cortisol and other corticosteroids in blood circulation. Here, we investigate the biological importance of the N-glycans of CBG derived from human serum by performing a structural and functional characterization of CBG N-glycosylation. Liquid chromatography-tandem MS-based glycoproteomics and glycomics combined with exoglycosidase treatment revealed 26 complex type N-glycoforms, all of which were terminated with α2,3-linked neuraminic acid (NeuAc) residues. The CBG N-glycans showed predominantly bi- and tri-antennary branching, but higher branching was also observed. N-glycans from all six N-glycosylation sites were identified with high site occupancies (70.5–99.5%) and glycoforms from all sites contained a relatively low degree of core-fucosylation (0–34.9%). CBG showed site-specific glycosylation and the site-to-site differences in core-fucosylation and branching could be in silico correlated with the accessibility to the individual glycosylation sites on the maturely folded protein. Deglycosylated and desialylated CBG analogs were generated to investigate the biological importance of CBG N-glycans. As a functional assay, MCF-7 cells were challenged with native and glycan-modified CBG and the amount of cAMP, which is produced as a quantitative response upon CBG binding to its cell surface receptor, was used to evaluate the CBG:receptor interaction. The removal of both CBG N-glycans and NeuAc residues increased the production of cAMP significantly. This confirms that N-glycans are involved in the CBG:receptor interaction and indicates that the modulation is performed by steric and/or electrostatic means through the terminal NeuAc residues. PMID:21558494

Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.

PubMed

Toor, Amir A; Sabo, Roy T; Roberts, Catherine H; Moore, Bonny L; Salman, Salman R; Scalora, Allison F; Aziz, May T; Shubar Ali, Ali S; Hall, Charles E; Meier, Jeremy; Thorn, Radhika M; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B; McCarty, John M; Chung, Harold M; Manjili, Masoud H; Neale, Michael C

2015-07-01

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Assessing immune competence in pigs by immunization with tetanus toxoid.

PubMed

Gimsa, U; Tuchscherer, A; Gimsa, J; Tuchscherer, M

2018-01-01

Immune competence can be tested by challenging organisms with a set of infectious agents. However, disease control requirements impose restrictions on the infliction of infections upon domestic pigs. Alternatively, vaccinations induce detectable immune responses that reflect immune competence. Here, we tested this approach with tetanus toxoid (TT) in young domestic pigs. To optimize the vaccination protocol, we immunized the pigs with a commercial TT vaccine at the age of 21 or 35 days. Booster immunizations were performed either 14 or 21 days later. TT-specific antibodies in plasma as well as lymphoproliferative responses were determined both 7 and 14 days after booster immunization using ELISA and lymphocyte transformation tests, respectively. In addition, general IgG and IgM plasma concentrations and mitogen-induced proliferation were measured. The highest TT-specific antibody responses were detected when blood samples were collected 1 week after a booster immunization conducted 21 days after primary immunization. The pigs' age at primary immunization did not have a significant influence on TT-specific antibody responses. Similarly, the TT-specific proliferative responses were highest when blood samples were collected 1 week after booster immunization, while age and time of primary and booster immunization were irrelevant in our setup. While general IgG and IgM plasma levels were highly age dependent, there were no significant age effects for TT-specific immune responses. In addition, mitogen-induced proliferation was independent of immunization as well as blood sampling protocols. In summary, our model of TT vaccination provides an interesting approach for the assessment of immune competence in young pigs. The detected vaccination effects were not biased by age, even though our data were acquired from immune systems that were under development during our tests.

Integrated Circuit Immunity

NASA Technical Reports Server (NTRS)

Sketoe, J. G.; Clark, Anthony

2000-01-01

This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

21 CFR 640.104 - Potency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... diphtheria, measles, and for at least one type of poliomyelitis. In the event the final bulk solution is... less than 2 units of diphtheria antitoxin per ml. (2) A measles neutralizing antibody level that, when... Biologics Evaluation and Research: (1) Reference Immune Globulin for correlation of measles antibody titers...

21 CFR 640.104 - Potency.

Code of Federal Regulations, 2013 CFR

2013-04-01

... diphtheria, measles, and for at least one type of poliomyelitis. In the event the final bulk solution is... less than 2 units of diphtheria antitoxin per ml. (2) A measles neutralizing antibody level that, when... Biologics Evaluation and Research: (1) Reference Immune Globulin for correlation of measles antibody titers...

21 CFR 640.104 - Potency.

Code of Federal Regulations, 2012 CFR

2012-04-01

... diphtheria, measles, and for at least one type of poliomyelitis. In the event the final bulk solution is... less than 2 units of diphtheria antitoxin per ml. (2) A measles neutralizing antibody level that, when... Biologics Evaluation and Research: (1) Reference Immune Globulin for correlation of measles antibody titers...

Immunization Program

Science.gov Websites

Department home page Immunizations Search: Search Toggle navigation Medical Services Disease Control Facebook Contacts CoverageRates Diseases Immunization Homepage Immunization Honor Roll HPV NDIIS Medical Providers

Integrated Immune Experiment

NASA Technical Reports Server (NTRS)

Crucian, Brian

2009-01-01

This viewgraph presentation reviews NASA's Integrated Immune Experiment. The objectives include: 1) Address significant lack of data regarding immune status during flight; 2) Replace several recent immune studies with one comprehensive study that will include in-flight sampling; 3) Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation; 4) Determine the clinical risk related to immune dysregulation for exploration class spaceflight; and 5) Determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

Addressing immunization registry population inflation in adolescent immunization rates.

PubMed

Robison, Steve G

2015-01-01

While U.S. adolescent immunization rates are available annually at national and state levels, finding pockets of need may require county or sub-county information. Immunization information systems (IISs) are one tool for assessing local immunization rates. However, the presence of IIS records dating back to early childhood and challenges in capturing mobility out of IIS areas typically leads to denominator inflation. We examined the feasibility of weighting adolescent immunization records by length of time since last report to produce more accurate county adolescent counts and immunization rates. We compared weighted and unweighted adolescent denominators from the Oregon ALERT IIS, along with county-level Census Bureau estimates, with school enrollment counts from Oregon's annual review of seventh-grade school immunization compliance for public and private schools. Adolescent immunization rates calculated using weighted data, for the state as a whole, were also checked against comparable National Immunization Survey (NIS) rates. Weighting individual records by the length of time since last activity substantially improved the fit of IIS data to county populations for adolescents. A nonlinear logarithmic (ogive) weight produced the best fit to the school count data of all examined estimates. Overall, the ogive weighted results matched NIS adolescent rates for Oregon. The problem of mobility-inflated counts of teenagers can be addressed by weighting individual records based on time since last immunization. Well-populated IISs can rely on their own data to produce adolescent immunization rates and find pockets of need.

Correlation between urinary GAG and anti-idursulfase ERT neutralizing antibodies during treatment with NICIT immune tolerance regimen: A case report☆,☆☆

PubMed Central

Kim, Sarah; Whitley, Chester B.; Jarnes Utz, Jeanine R.

2018-01-01

Introduction Antibodies to intravenous idursulfase enzyme replacement therapy (ERT) for patients with Hunter syndrome (mucopolysaccharidosis type II, MPS II) can have a harmful clinical impact, including both increasing risk of infusion reactions and inhibiting therapeutic activity. Thus, failure to monitor anti-idursulfase antibodies and neutralizing antibodies, and delays in reporting results, may postpone critical clinical decisions. Hypothesis Urinary glycosaminoglycan (GAG) levels may be used as a biomarker for anti-idursulfase antibodies and neutralizing antibodies to improve timeliness in monitoring and managing ERT. Methods This is a case report describing a patient with MPS II with high levels of neutralizing antibodies and worsened clinical status who was treated for five years with a non-immunosuppressive and non-cytotoxic immune tolerance (NICIT) regimen, consisting of intravenous immune globulin and frequent infusions of idursulfase. Neutralizing antibodies and total anti-idursulfase antibodies were measured by two different methods, the direct 1,9-dimethylmethylene blue (DMB) assay and cetylpyridinium chloride carbazole-borate (CPC) assay. Results Neutralizing antibodies, measured as percent inhibition of enzyme activity and also by total neutralizing antibody titer, were correlated with quantitative urinary GAG measured by DMB assay (p = 0.026, p = 0.0067), and quantitative urinary GAG by CPC assay with percent inhibition of enzyme activity by neutralizing antibodies (p = 0.0475). The NICIT regimen showed a sustained immune tolerance after five years and was well-tolerated. Conclusions Urinary GAG, measured by DMB assay, may be a biomarker for anti-idursulfase neutralizing antibodies and is useful for managing immune tolerance regimens for patients with MPS II who have high levels of anti-idursulfase neutralizing antibodies. This study highlights the importance of regular and frequent monitoring of urinary GAG in patients with MPS II who are

Sex hormone-binding globulin regulation of androgen bioactivity in vivo: validation of the free hormone hypothesis

PubMed Central

Laurent, Michaël R.; Hammond, Geoffrey L.; Blokland, Marco; Jardí, Ferran; Antonio, Leen; Dubois, Vanessa; Khalil, Rougin; Sterk, Saskia S.; Gielen, Evelien; Decallonne, Brigitte; Carmeliet, Geert; Kaufman, Jean-Marc; Fiers, Tom; Huhtaniemi, Ilpo T.; Vanderschueren, Dirk; Claessens, Frank

2016-01-01

Sex hormone-binding globulin (SHBG) is the high-affinity binding protein for androgens and estrogens. According to the free hormone hypothesis, SHBG modulates the bioactivity of sex steroids by limiting their diffusion into target tissues. Still, the in vivo physiological role of circulating SHBG remains unclear, especially since mice and rats lack circulating SHBG post-natally. To test the free hormone hypothesis in vivo, we examined total and free sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transgene. SHBG increased total androgen and estrogen concentrations via hypothalamic-pituitary feedback regulation and prolonged ligand half-life. Despite markedly raised total sex steroid concentrations, free testosterone was unaffected while sex steroid bioactivity on male and female reproductive organs was attenuated. This occurred via a ligand-dependent, genotype-independent mechanism according to in vitro seminal vesicle organ cultures. These results provide compelling support for the determination of free or bioavailable sex steroid concentrations in medicine, and clarify important comparative differences between translational mouse models and human endocrinology. PMID:27748448

Bibliography of Germfree Research 1885-1963. 1979 Supplement,

DTIC Science & Technology

1979-01-01

1):244-249, 1979. (Ja) -6- J_1 102. Jaroskova, L., Trebichavsky, I., Kovaru, F. and Prokesova, L. Membrane immuno- globulins in pig foetuses and... foetus as a germ- free model in the study of development of cellular and humoral immunity. Folia Microbiologica. 24(1) :78-79, 1979. 190. Pozharisskii

Effect of endosulfan on immunological competence of layer birds.

PubMed

Singh, P P; Kumar, Ashok; Chauhan, R S; Pankaj, P K

2016-07-01

The present study was aimed to investigate the immunological competence of endosulfan insecticide after limited oral administration in White Leghorn layer chickens. A total of 20 White Leghorn birds were given endosulfan in drinking water at 30 ppm/bird/day (no observable effect level dose) for a period of 3-months. Immune competence status of layer birds and chicks hatched from endosulfan offered birds were estimated at 15-day interval in layer birds and at monthly interval in chicks using immunological, biochemical parameters, and teratological estimates. There was a significant decrease in levels of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds fed with endosulfan as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with endosulfan as compared to control. Subsequently, chicks produced from endosulfan-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. The exposure to endosulfan in limited oral dosage was able to exhibit hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting cautious usage of endosulfan insecticide in poultry sheds.

Measuring polio immunity to plan immunization activities.

PubMed

Voorman, Arend; Lyons, Hil M

2016-11-21

The Global Polio Eradication Initiative is closer than ever to achieving a polio-free world. Immunization activities must still be carried out in non-endemic countries to maintain population immunity at levels which will stop poliovirus from spreading if it is re-introduced from still-infected areas. In areas where there is no active transmission of poliovirus, programs must rely on surrogate indicators of population immunity to determine the appropriate immunization activities, typically caregiver-reported vaccination history obtained from non-polio acute flaccid paralysis patients identified through polio surveillance. We used regression models to examine the relationship between polio vaccination campaigns and caregiver-reported polio vaccination history. We find that in many countries, vaccination campaigns have a surprisingly weak impact on these commonly used indicators. We conclude that alternative criteria and data, such as routine immunization indicators from vaccination records or household surveys, should be considered for planning polio vaccination campaigns, and that validation of such surrogate indicators is necessary if they are to be used as the basis for program planning and risk assessment. We recommend that the GPEI and similar organizations consider or continue devoting additional resources to rigorously study population immunity and campaign effectiveness in at-risk countries. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Rabbit antithymocyte globulin is more beneficial in standard kidney than in extended donor recipients.

PubMed

Hardinger, Karen L; Brennan, Daniel C; Schnitzler, Mark A

2009-05-15

In a randomized, international study comparing rabbit antithymocyte globulin (TMG) and basiliximab (BAS) induction in renal transplant recipients at risk for delayed graft function or acute rejection (n=278), TMG was associated with less acute rejection at 1 year. This study analyzed outcomes stratified by standard criteria donor (SCD), extended criteria donor (ECD), and hypertensive donor. Data-capture limitations necessitated defining ECD as donor age more than 60 years or 50 to 60 years with hypertension and renal insufficiency. Seventy-five recipients received ECD-kidneys (28.4% TMG vs. 25.6% BAS, P=NS) and 203 recipients received SCD-kidneys (72.6% TMG vs. 74.4% BAS, P=NS). Recipients of an ECD or hypertensive donor-kidney had similar outcomes between treatment groups. Recipients of an SCD-kidney treated with TMG had less rejection (odds ratio [OR] 0.48). Recipients of a normotensive donor-kidney treated with TMG had less rejection (OR 0.56). Recipients of a normotensive, SCD-kidney treated with TMG had less rejection (OR 0.47) and death (OR 0.17) than their counterparts treated with BAS. Contrary to its perceived niche in recipients of ECD-kidneys, TMG was most beneficial in patients who received a normotensive, deceased SCD kidney.

The flip side of immune surveillance: immune dependency.

PubMed

Prehn, Richmond T; Prehn, Liisa M

2008-04-01

The growths of many and perhaps all tumors may be stimulated rather than inhibited by a quantitatively low level of immunity. The reason tumors have antigens may be that tumors do not develop in vivo in the absence of at least a minimal immune reaction; in this sense, cancer may be considered an autoimmune disease. This review, based largely on the work of our own laboratory, outlines the data showing that the titration of anti-tumor immunity exhibits the phenomenon of hormesis, i.e. the dose-response curve is non-linear such that low levels of immunity are generally stimulatory but larger quantities of the same immune reactants may inhibit tumor growth. Evidence is also reviewed that suggests that the immune response may vary qualitatively and quantitatively during progression, such that there seems to be, during oncogenesis, a very low level of immune reaction that aids initial tumor growth, followed by a larger reaction that may cause remission of early neoplasms, followed, if the neoplasm survives, by a relative immunologic tolerance to the tumor that may be dependent, at least in part, on suppressor cells. This knowledge may help to explain some clinical observations concerning the relationships among tumor types and the organ distribution of metastases.

Immunizations challenge healthcare personnel and affects immunization rates.

PubMed

Strohfus, Pamela K; Kim, Susan C; Palma, Sara; Duke, Russell A; Remington, Richard; Roberts, Caleb

2017-02-01

This study measured 1. medical office immunization rates and 2. health care personnel competency in managing vaccine practices before and after evidence-based immunization education was provided. This descriptive study compared 32 family medicine and pediatric offices and 178 medical assistants, licensed practical nurses, registered nurses, nurse practitioners, and physicians in knowledge-based testing pre-education, post-education, and 12-months post-education. Immunization rates were assessed before and 18-months post-education. Immunization rates increased 10.3% - 18months post-education; knowledge increased 7.8% - 12months post-education. Family medicine offices, licensed practical nurses, and medical assistants showed significant knowledge deficits before and 12-months post-education. All demographic groups scored less in storage/handling 12-months post-education. This study is one of the first studies to identify competency challenges in effective immunization delivery among medical assistants, licensed practical nurses, and family medicine offices. Formal and continuous education in immunization administration and storage/handling is recommended among these select groups. Copyright © 2016 Elsevier Inc. All rights reserved.

Toll immune signal activates cellular immune response via eicosanoids.

PubMed

Shafeeq, Tahir; Ahmed, Shabbir; Kim, Yonggyun

2018-07-01

Upon immune challenge, insects recognize nonself. The recognition signal will propagate to nearby immune effectors. It is well-known that Toll signal pathway induces antimicrobial peptide (AMP) gene expression. Eicosanoids play crucial roles in mediating the recognition signal to immune effectors by enhancing humoral immune response through activation of AMP synthesis as well as cellular immune responses, suggesting a functional cross-talk between Toll and eicosanoid signals. This study tested a cross-talk between these two signals. Two signal transducing factors (MyD88 and Pelle) of Toll immune pathway were identified in Spodoptera exigua. RNA interference (RNAi) of either SeMyD88 or SePelle expression interfered with the expression of AMP genes under Toll signal pathway. Bacterial challenge induced PLA 2 enzyme activity. However, RNAi of these two immune factors significantly suppressed the induction of PLA 2 enzyme activity. Furthermore, RNAi treatment prevented gene expression of cellular PLA 2 . Inhibition of PLA 2 activity reduced phenoloxidase activity and subsequent suppression in cellular immune response measured by hemocyte nodule formation. However, immunosuppression induced by RNAi of Toll signal molecules was significantly reversed by addition of arachidonic acid (AA), a catalytic product of PLA 2 . The addition also significantly reduced the enhanced fungal susceptibility of S. exigua treated by RNAi against two Toll signal molecules. These results indicate that there is a cross-talk between Toll and eicosanoid signals in insect immunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of HBIG combined with hepatitis B vaccine on blocking HBV transmission between mother and infant and its effect on immune cells.

PubMed

Gong, Junling; Liu, Xing

2018-01-01

The effect of hepatitis B immune globulin (HBIG) combined with hepatitis B vaccine on blocking hepatitis B virus (HBV) transmission between mother and infant and its effect on immune cells were studied. Ninety newborn infants confirmed to be HBV surface antigen (HBsAg)-positive were divided equally into three groups. Group A newborns received the hepatitis B vaccine at 0, 1 and 6 months after birth (10 µg/time). Group B newborns received an intramuscular injection of 100 IU HBIG 2 h after birth before the same treatment as group A. Mothers of group C newborns received three gluteus maxinus injections of 200 IU HBIG. The newborns in group C got the same treatment as group B. The blocking effect of HBV transmission between mother and infant was evaluated, and cell immune function was assessed. There were significant differences in comparison of blocking success rates between group A and B, and between group A and C as well (p<0.05). At the end of 12 months follow-up, the CD4 + level and CD4 + /CD8 + ratio in group C were higher thanthose in group A and B (p<0.05). In addition, the level of CD8 + T lymphocyte in group C was lower than those in group A and B (p<0.05). In comparison of levels of CD4 + T lymphocyte at the end of 12 months follow-up and 24 h after birth, the differences were significant (p<0.05) in bothgroup B and C. The differences of IFN-γ levels betweengroups B/C and group A were significant (p<0.05). Forthose newborn infants born to mothers who were positivefor both HBsAg and HBeAg, HBIG intervention formothers during late pregnancy, together with combinedtreatment of HBIG and hepatitis B vaccine for infants, gavebetter blocking result of HBV transmission.

Control of adaptive immunity by the innate immune system.

PubMed

Iwasaki, Akiko; Medzhitov, Ruslan

2015-04-01

Microbial infections are recognized by the innate immune system both to elicit immediate defense and to generate long-lasting adaptive immunity. To detect and respond to vastly different groups of pathogens, the innate immune system uses several recognition systems that rely on sensing common structural and functional features associated with different classes of microorganisms. These recognition systems determine microbial location, viability, replication and pathogenicity. Detection of these features by recognition pathways of the innate immune system is translated into different classes of effector responses though specialized populations of dendritic cells. Multiple mechanisms for the induction of immune responses are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate effector responses. Here we discuss these emerging principles of innate control of adaptive immunity.

Immunity by equilibrium.

PubMed

Eberl, Gérard

2016-08-01

The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

Trained immunity: a program of innate immune memory in health and disease

PubMed Central

Netea, Mihai G.; Joosten, Leo A.B.; Latz, Eicke; Mills, Kingston H.G.; Natoli, Gioacchino; Stunnenberg, Hendrik G.; O’Neill, Luke A.J.; Xavier, Ramnik J.

2016-01-01

The general view that only adaptive immunity can build immunological memory has recently been challenged. In organisms lacking adaptive immunity as well as in mammals, the innate immune system can mount resistance to reinfection, a phenomenon termed trained immunity or innate immune memory. Trained immunity is orchestrated by epigenetic reprogramming, broadly defined as sustained changes in gene expression and cell physiology that do not involve permanent genetic changes such as mutations and recombination, which are essential for adaptive immunity. The discovery of trained immunity may open the door for novel vaccine approaches, for new therapeutic strategies for the treatment of immune deficiency states, and for modulation of exaggerated inflammation in autoinflammatory diseases. PMID:27102489

Immune evasion, immunopathology and the regulation of the immune system.

PubMed

Sorci, Gabriele; Cornet, Stéphane; Faivre, Bruno

2013-02-13

Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths) that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

A novel mutation causing complete thyroxine-binding globulin deficiency (TBG-CD-Negev) among the Bedouins in southern Israel.

PubMed

Miura, Y; Hershkovitz, E; Inagaki, A; Parvari, R; Oiso, Y; Phillip, M

2000-10-01

T4-binding globulin (TBG) is the major thyroid hormone transport protein in human serum. Inherited TBG abnormalities do not usually alter the metabolic status and are transmitted in X-linked inheritance. A high prevalence of complete TBG deficiency (TBG-CD) has been reported among the Bedouin population in the Negev (southern Israel). In this study we report a novel single mutation causing complete TBG deficiency due to a deletion of the last base of codon 38 (exon 1), which led to a frame shift resulting in a premature stop at codon 51 and a presumed truncated peptide of 50 residues. This new variant of TBG (TBG-CD-Negev) was found among all of the patients studied. We conclude that a single mutation may account for TBG deficiency among the Bedouins in the Negev. This report is the first to describe a mutation in a population with an unusually high prevalence of TBG-CD.

Low dose anti-thymocyte globulin reduces chronic graft-versus-host disease incidence rates after matched unrelated donor transplantation.

PubMed

Tandra, Anand; Covut, Fahrettin; Cooper, Brenda; Creger, Richard; Brister, Lauren; McQuigg, Bernadette; Caimi, Paolo; Malek, Ehsan; Tomlinson, Ben; Lazarus, Hillard M; Otegbeye, Folashade; Kolk, Merle; de Lima, Marcos; Metheny, Leland

2017-12-04

Anti-thymocyte globulin (ATG) is often added to hematopoietic stem cell transplant conditioning regimens to prevent graft rejection and reduce graft-versus-host disease (GVHD). Doses used in retrospective and prospective clinical trials have ranged from 2.5 to 20 mg/kg with rates of grade II-IV acute GVHD and chronic GVHD up to 40 and 60%, respectively. We retrospectively compared outcomes in recipients of matched unrelated donor (MUD) grafts given low dose rabbit ATG IV 3 mg/kg (n = 52) versus recipients of matched related donor (MRD) grafts (n = 48) without ATG. One year cumulative incidence of chronic GVHD was 25.2% in the MUD group versus 33.3% in the MRD group (p = .5). One-year cumulative incidence of extensive chronic GVHD was 9.6% in the MUD group versus 26.6% in the MRD group (p = .042). Our analysis supports the use of low dose ATG in MUD transplantation as an effective therapy to prevent chronic GVHD.

Universal immunity to influenza must outwit immune evasion

PubMed Central

Quiñones-Parra, Sergio; Loh, Liyen; Brown, Lorena E.; Kedzierska, Katherine; Valkenburg, Sophie A.

2014-01-01

Although an influenza vaccine has been available for 70 years, influenza virus still causes seasonal epidemics and worldwide pandemics. Currently available vaccines elicit strain-specific antibody (Ab) responses to the surface haemagglutinin (HA) and neuraminidase (NA) proteins, but these can be ineffective against serologically-distinct viral variants and novel subtypes. Thus, there is a great need for cross-protective or “universal” influenza vaccines to overcome the necessity for annual immunization against seasonal influenza and to provide immunity to reduce the severity of infection with pandemic or outbreak viruses. It is well established that natural influenza infection can provide cross-reactive immunity that can reduce the impact of infection with distinct influenza type A strains and subtypes, including H1N1, H3N2, H2N2, H5N1, and H7N9. The key to generating universal influenza immunity through vaccination is to target functionally-conserved regions of the virus, which include epitopes on the internal proteins for cross-reactive T cell immunity or on the HA stem for broadly reactive Ab responses. In the wake of the 2009 H1N1 pandemic, broadly neutralizing antibodies (bnAbs) have been characterized and isolated from convalescent and vaccinated individuals, inspiring development of new vaccination techniques to elicit such responses. Induction of influenza-specific T cell responses through vaccination has also been recently examined in clinical trials. Strong evidence is available from human and animal models of influenza to show that established influenza-specific T cell memory can reduce viral shedding and symptom severity. However, the published evidence also shows that CD8+ T cells can efficiently select immune escape mutants early after influenza virus infection. Here, we discuss universal immunity to influenza viruses mediated by both cross-reactive T cells and Abs, the mechanisms of immune evasion in influenza, and propose how to counteract

Effect of Excoecaria agallocha on non-specific immune responses and disease resistance of Oreochromis niloticus against Streptococcus agalactiae.

PubMed

Laith, A A; Mazlan, A G; Effendy, A W; Ambak, M A; Nurhafizah, W W I; Alia, A S; Jabar, A; Najiah, M

2017-06-01

The current study was designed to evaluate the effects of Excoecaria agallocha leaf extracts on immune mechanisms and resistance of tilapia, Oreochromis niloticus, after challenge with Streptococcus agalactiae. Fish were divided into 6 groups; groups 1-5 fed with E. agallocha leaf extracts at 10, 20, 30, 40 and 50mgkg -1 level, respectively. Group 6 were fed without extract addition and acted as control. E. agallocha extracts were administered as feed supplement in fish diet for 28days and the hematological, immunological, and growth performance studies were conducted. Fish were infected with S. agalactiae at a dose of 15×105CFUmL -1 and the total white blood cell (WBC), phagocytosis and respiratory burst activities of leukocytes, serum bactericidal activity, lysozyme, total protein, albumin, and globulin levels were monitored and mortalities recorded for 15days post infection. Results revealed that feeding O. niloticus with 50mgkg -1 of E. agallocha enhanced WBC, phagocytic, respiratory burst, serum bactericidal and lysozyme activities on day 28 pre-challenge and on 3rd, 6th, 9th, 12th and 15th day post-challenge as compared to control. Total protein and albumin were not enhanced by E. agallocha diet. E. agallocha increased the survival of fish after challenge with S. agalactiae. The highest mortality rate (97%) was observed in control fish and the lowest mortality (27%) was observed with group fed with 50mgkg -1 extract. The results indicate that dietary intake of E. agallocha methanolic leaf extract in O. niloticus enhances the non-specific immunity and disease resistance against S. agalactiae pathogen. Copyright © 2017. Published by Elsevier Ltd.

Immunity's fourth dimension: approaching the circadian-immune connection.

PubMed

Arjona, Alvaro; Silver, Adam C; Walker, Wendy E; Fikrig, Erol

2012-12-01

The circadian system ensures the generation and maintenance of self-sustained ~24-h rhythms in physiology that are linked to internal and environmental changes. In mammals, daily variations in light intensity and other cues are integrated by a hypothalamic master clock that conveys circadian information to peripheral molecular clocks that orchestrate physiology. Multiple immune parameters also vary throughout the day and disruption of circadian homeostasis is associated with immune-related disease. Here, we discuss the molecular links between the circadian and immune systems and examine their outputs and disease implications. Understanding the mechanisms that underlie circadian-immune crosstalk may prove valuable for devising novel prophylactic and therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Trends in Outcomes and Hospitalization Charges of Infant Botulism in the United States: A Comparative Analysis Between Kids' Inpatient Database and National Inpatient Sample.

PubMed

Opila, Tamara; George, Asha; El-Ghanem, Mohammad; Souayah, Nizar

2017-02-01

New therapeutic strategies, including immune globulin intravenous, have emerged in the past two decades for the management of botulism. However, impact on outcomes and hospitalization charges among infants (aged ≤1 year) with botulism in the United States is unknown. We analyzed the Kids' Inpatient Database (KID) and National Inpatient Sample (NIS) for in-hospital outcomes and charges for infant botulism cases from 1997 to 2009. Demographics, discharge status, mortality, length of stay, and hospitalization charges were reported from the two databases and compared. Between 1997 and 2009, 504 infant hospitalizations were captured in KID', and 340 hospitalizations from NIS, for comparable years. A significant decrease was observed in mean length of stay for 'KID (P < 0.01); a similar decrease was observed for the NIS. The majority of patients were discharged to home. Despite an initial decrease after 1997, an increasing trend was observed for 'KID/NIS mean hospital charges from 2000 to 2009 (from $57,659/$56,309 to $143,171/$106,378; P < 0.001/P < 0.001). A linear increasing trend was evident when examining mean daily hospitalization charges for both databases. In conducting a subgroup analysis of the 'KID database, the youngest patients with infantile botulism (≤1.9 months) displayed the highest average number of procedures during their hospitalization (P < .001) and the highest rate of mechanical ventilation (P < .001), compared with their older counterparts. Infant botulism cases have demonstrated a significant increase in hospitalization charges over the years despite reduced length of stay. Additionally, there were significantly higher daily adjusted hospital charges and an increased rate of routine discharges for immune globulin intravenous-treated patients. More controlled studies are needed to define the criteria for cost-effective use of intravenous immune globulin in the population with infant botulism. Copyright © 2016 Elsevier Inc. All

BERNA: a century of immunobiological innovation.

PubMed

Cryz, S J

1999-10-01

At the time the Swiss Serum and Vaccine Institute Berne (BERNA) was found in 1898, few vaccines or immune globulins were available. This short list included vaccines against cholera, typhoid fever, plague, smallpox and rabies and equine anti-tetanus and diphtheria immune globulins. Furthermore, their use was restricted due to limited production capacity, uncertainty regarding safety and no public health infrastructure to promote their utilization. Today, safe and effective vaccines exist for more than 30 infectious diseases while human hyperimmune globulins exist to treat or prevent rabies, tetanus, respiratory syncytial virus, cytomegalovirus, hepatitis A, hepatitis B, and herpes virus (Varicella zoster) infections. Throughout its 100 years of existence, BERNA has played a key role in the evolution of the field by introducing novel technology leading to safer, and more efficacious vaccines. It was a pioneer in the development of freeze dried smallpox vaccine free from bacterial contamination. The Salmonella typhi Ty21a typhoid fever vaccine strain demonstrated that oral immunization against enteric bacterial pathogens was not only feasible, but could be accomplished with a virtual lack of attendant adverse reactions. This finding has served as an impetus to develop other live attenuated bacterial strains not only as vaccines, but also as vectors for vaccine antigens and gene therapy. One such example is Vibrio cholerae CVD 103-HgR, the first live vaccine for human use derived through recombinant DNA technology. Subsequent studies have shown that these two vaccine strains can be combined without sacrificing safety or immunogenicity, setting the cornerstone for combined orally administered vaccines. Recently, a novel vaccine antigen delivery system, termed virosomes, has been utilized to construct hepatitis A and influenza vaccines. Such vaccines elicit fewer local adverse reactions than their classical counterparts and display enhanced immunogenicity. Virosome

The twilight of immunity: emerging concepts in aging of the immune system.

PubMed

Nikolich-Žugich, Janko

2018-01-01

Immunosenescence is a series of age-related changes that affect the immune system and, with time, lead to increased vulnerability to infectious diseases. This Review addresses recent developments in the understanding of age-related changes that affect key components of immunity, including the effect of aging on cells of the (mostly adaptive) immune system, on soluble molecules that guide the maintenance and function of the immune system and on lymphoid organs that coordinate both the maintenance of lymphocytes and the initiation of immune responses. I further address the effect of the metagenome and exposome as key modifiers of immune-system aging and discuss a conceptual framework in which age-related changes in immunity might also affect the basic rules by which the immune system operates.

Low capacity of erythrocytes to bind with immune complexes via C3b receptor in patients with systemic lupus erythematosus: correlation with pathological proteinuria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nojima, Y.; Terai, C.; Minota, S.

1985-01-01

Erythrocytes from 51 patients with systemic lupus erythematosus and 75 controls were tested for the capacity to bind aggregated human gamma-globulin labeled with radioiodine in the presence of complement. Both in patients and controls, a trimodal distribution of binding capacity was observed. Low (less than 9% of the added radioactivity), intermediate (9-17%), and high binding (more than 17%) were observed in 13, 58, and 29% in controls and in 49, 43 and 8% in lupus patients. The low binding capacity of erythrocytes persisted even after patients entered remission following steroid therapy. A genetic control of binding capacity was supported bymore » familial surveys. Prevalence of pathological proteinuria was significantly higher in patients with low binding capacity than those with intermediate or high binding capacity (16/25 vs 7/26, P less than 0.01). These results indicate that an impaired physiological disposal of immune complexes via the erythrocyte C3b receptor in lupus patients may contribute to the development of renal involvement.« less

Winter distribution and abundance of Snowy Plovers in eastern North America and the West Indies

USGS Publications Warehouse

Elliott-Smith, Elise; Haig, Susan M.; Ferland, C.L.; Gorman, Leah

2004-01-01

Serum protein changes were studied in immune and nonimmune pigeons infected with three different strains of Trichomonas gallinae. Strain I (nonvirulent) produced no change in the relative concentration of serum components. Strains II (oral canker) and III (Jones' Barn) produced decreases in albumin and alpha globulins, and increases in beta and gamma globulins between the 7th and 20th days post infection. Birds infected with strain II began to return to normal by the 20th day, while all those infected with strain III were dead between 10 and 14 days post infection. Two serum protein patterns resulted from infection of immune birds with the Jones' Barn strain. One showed no change in relative protein concentrations and no tissue invasion by the parasite while the other was similar to that seen in nonimmune birds infected with a strain producing oral canker. These also showed evidence of tissue invasion by the parasite. It was concluded that tissue invasion was necessary to evoke a quantitative change in serum protein concentrations.

Immune modulation following immunization with polyvalent vaccines in dogs.

PubMed

Strasser, Alois; May, Bettina; Teltscher, Andrea; Wistrela, Eva; Niedermüller, Hans

2003-08-15

A decline in T-cell-mediated immunity and transient state of immunosuppression after immunization has been reported in dogs. Nevertheless, dogs are still routinely vaccinated with polyvalent live vaccines and severe disease does not generally occur. In order to investigate these effects on the canine immune system and to elucidate possible mechanisms we determined the following immune parameters in the blood of 33 clinically sound German shepherd dogs before and after standard vaccination with a polyvalent vaccine against distemper, parvovirus, viral hepatitis, leptospirosis, kennel cough and rabies: white and differential blood cell count, the serum concentrations and/or activities of IL-1, IL-2, IFN-gamma, TNF-alpha, neopterin and IgG, natural killer (NK) cell activity, bactericidal activity and complement hemolytic activity, lymphocyte proliferation test (LPT) and nitroblue tetrazolium test (NBT). Our major findings were that significant postvaccinal decreases in T-cell mitogenic response to PHA and in neutrophil function and neopterin serum concentration were accompanied by simultaneous increase in plasma IgG and hemolytic complement activity. This suggests a transient shift in the balance between cell-mediated and humoral (T(H)1/T(H)2) immunity rather than immunosuppression. These results do not imply that dogs should not receive live vaccines, as the response to vaccines just seems to create a state of altered homeostasis when immunization elicits protection by humoral and cell-mediated immunity. However, these recognized compromises of immune function should be considered and vaccines still be applied only in healthy animals and strictly according to the rules and regulations given by the manufacturer.

Prognostic value of pretreatment albumin/globulin ratio in digestive system cancers: A meta-analysis.

PubMed

Guo, Hui-Wen; Yuan, Tang-Zhan; Chen, Jia-Xi; Zheng, Yang

2018-01-01

The albumin/globulin ratio (AGR) has been widely reported to be a potential predictor of prognosis in digestive system cancers (DSCs), but convincing conclusions have not been made. Therefore, herein, we performed a meta-analysis of relevant studies regarding this topic to evaluate the prognostic value of AGR in patients with DSCs. Three databases, including PubMed, EMBase, and Web of science, were searched comprehensively for eligible studies through September 8, 2017. The outcomes of interest included overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). In our meta-analysis, pooled analysis of 13 studies with 9269 patients showed that a low AGR was significantly correlated with poor OS (HR = 1.94; 95% CI: 1.57-2.38; P <0.001). Five studies with 6538 participants involved DFS, and our pooled analysis of these studies also demonstrated that there was a significant association of a low AGR with worse DFS (HR = 1.49; 95% CI: 1.10 to 2.00; P < 0.001). In addition, only 2 studies referred to CSS, and we also detected a significant relationship between a low AGR and worse CSS from the results of our meta-analysis. In summary, a low pretreatment AGR was related to unfavorable survival in human digestive system cancers. A low pretreatment AGR may be a useful predictive prognostic biomarker in human digestive system cancers.

[Changes in molecular forms of sex hormone binding globulin during menstrual cycle and menopause].

PubMed

Fonseca, M E; Masón, M; Ochoa, R; Hernández-V, M; Zárate, A

1996-11-01

Sex hormone binding globulin (SHBG) is a glycoprotein that transports mainly androgens and estrogens regulating the amount of free and bound hormone which in turn plays a role in the metabolic balance. It is also known that estrogens increase the hepatic production of SHBG which circulates in various molecular forms containing different amounts of sialic acid as the main component of carbohydrates. In the present work we studied physiological variations of molecular forms of SHBG during the normal menstrual cycle and the menopause. During the follicular phase the form 54 KD was the predominant variant, in the periovulatory period was isomers 90 KD, and during the luteal phase corresponded to both 54 and 90 KD. In the menopause dimeric form of 90 KD corresponded to the major proportion and was present a higher molecular forms of 115-135 KD. Following estrogen therapy the chromatographic profile changed as to that observed during the menstrual cycle. Important changes in the proportion of sialic acid were observed in each of the phases of menstrual cycle and following estrogen replacement. And increase in the amount of sialic acid corresponded to higher estrogen concentrations. It is concluded that SHBG concentrations varies during the menstrual cycle according the estrogen levels which in addition regulates the proportion of molecular forms and sialic acid containt.

Pharmacokinetic and pharmacodynamic studies of two different rabbit antithymocyte globulin dosing regimens: results of a randomized trial.

PubMed

Büchler, Matthias; Longuet, Hélène; Lemoine, Roxane; Herr, Florence; Gatault, Philippe; Thibault, Gilles; Ternant, David; Foulon, Christine; Pilorge, Bernadette; Lemay, Djamila; Sung, Crystal; Halimi, Jean-Michel; Baron, Christophe; Lebranchu, Yvon

2013-03-01

Rabbit antithymocyte globulin (rATG; Thymoglobulin(®)) is currently used to prevent acute rejection in kidney transplantation. The dose and regimen of rATG have not been optimized. Moreover, the impact of different treatment regimens on T-cell phenotype reconstitution remains unknown. We conducted a prospective randomized study of 17 renal transplant patients to determine the pharmacokinetics of total and active (bound to human cells) rATG and T-cell phenotype reconstitution after rATG administration. Patients received rATG at a total dose of 6mg/kg, administered either as 1.5mg/kg/day on days 0-3 (Group 1, n=8) or 3mg/kg on days 0 and 3 (Group 2, n=9). All patients received tacrolimus, mycophenolate mofetil and steroids. Blood samples were assayed for total rATG by enzyme linked immunosorbent assay and active rATG by flow cytometry. Maximum concentrations and terminal half-lives were similar between the two groups but at month 3 Group 1 had significantly lower values for total rATG (concentration was 6.2±1.1μg/mL versus 10.2±2.9μg/mL in Group 2, p=0.027) and total rATG dose-normalized AUC (374±83dayg/mL versus 508±149dayg/mL in Group 2, p=0.046). Time to sub-therapeutic levels (<1μg/mL) of active rATG was significantly shorter in Group 1 (18.75±6.9days versus 20±7.5days in Group 2, p<0.001). rATG induced significant depletion followed by slow reconstitution of CD3(+), CD4(+) and CD8(+) cells, with no marked differences between groups. B-cell count was unaffected, whereas CD3(-)CD56(+) NK-cell depletion was observed in both groups. rATG induced a significant decrease in the proportion of naïve CD4(+) T-cells, which plateaued after month 1 in Group 1 and after month 6 in Group 2. The proportion of central memory CD4(+) T-cells increased to a similar extent in both groups (Group 1: 38±18% at baseline, 74±23% at one year, p=0.009; Group 2: 32±14% at baseline, 65±14% at one year, p=0.001). In conclusion, our results suggest that the dosing regimen for r

Late Pregnancy Thyroid-Binding Globulin Predicts Perinatal Depression

PubMed Central

Pedersen, Cort; Leserman, Jane; Garcia, Nacire; Stansbury, Melissa; Meltzer-Brody, Samantha; Johnson, Jacqueline

2016-01-01

Previously we found that late pregnancy total and free thyroxine (TT4, FT4) concentrations were negatively related to greater pre and/or postpartum depressive symptoms. In a much larger cohort, the current study examined whether these thyroid indices measured earlier in the third trimester (31-33 weeks) predict subsequent perinatal depression and anxiety ratings as well as syndromal depression. Thyroid-binding globulin (TBG) concentrations increase markedly during pregnancy and may be an index of sensitivity to elevated estrogen levels. TBG was examined in this study because prior findings suggest that postpartum depression is related to sensitivity to mood destabilization by elevated sex hormone concentrations during pregnancy. Our cohort was 199 euthyroid women recruited from a public health obstetrics clinic (63.8% Hispanic, 21.6% Black). After screening and blood draws for hormone measures at pregnancy weeks 31-33, subjects were evaluated during home visits at pregnancy weeks 35-36 as well as postpartum weeks 6 and 12. Evaluations included psychiatric interviews for current and life-time DSM-IV psychiatric history (M.I.N.I.-Plus), subject self-ratings and interviewer ratings for depression and anxiety (Edinburgh Postnatal Depression Scale, Montgomery-Ǻsberg Depression Rating Scale; Spielberger State-Trait Anxiety Inventory, Hamilton Anxiety Inventory), as well as a standardized interview to obtain life-time trauma history. Numerous covariates were included in all regression analyses. Trauma and major depression history were robustly significant predictors of depression and anxiety ratings over the study period when these variables were analyzed individually or in a combined model including FT4 or TBG (p<.001). When analyzed alone, FT4 levels were a less strong but still significant predictor of all depression and anxiety ratings (p<.05) while TBG levels was a significant or nearly significant predictor of most ratings. FT4, TBG and trauma history, but not

Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity

PubMed Central

Rosado, Maria Manuela; Simkó, Myrtill; Mattsson, Mats-Olof; Pioli, Claudio

2018-01-01

In recent years, the effects of electromagnetic fields (EMFs) on the immune system have received a considerable interest, not only to investigate possible negative health impact but also to explore the possibility to favorably modulate immune responses. To generate beneficial responses, the immune system should eradicate pathogens while “respecting” the organism and tolerating irrelevant antigens. According to the current view, damage-associated molecules released by infected or injured cells, or secreted by innate immune cells generate danger signals activating an immune response. These signals are also relevant to the subsequent activation of homeostatic mechanisms that control the immune response in pro- or anti-inflammatory reactions, a feature that allows modulation by therapeutic treatments. In the present review, we describe and discuss the effects of extremely low frequency (ELF)-EMF and pulsed EMF on cell signals and factors relevant to the activation of danger signals and innate immunity cells. By discussing the EMF modulating effects on cell functions, we envisage the use of EMF as a therapeutic agent to regulate immune responses associated with wound healing. PMID:29632855

Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity.

PubMed

Rosado, Maria Manuela; Simkó, Myrtill; Mattsson, Mats-Olof; Pioli, Claudio

2018-01-01

In recent years, the effects of electromagnetic fields (EMFs) on the immune system have received a considerable interest, not only to investigate possible negative health impact but also to explore the possibility to favorably modulate immune responses. To generate beneficial responses, the immune system should eradicate pathogens while "respecting" the organism and tolerating irrelevant antigens. According to the current view, damage-associated molecules released by infected or injured cells, or secreted by innate immune cells generate danger signals activating an immune response. These signals are also relevant to the subsequent activation of homeostatic mechanisms that control the immune response in pro- or anti-inflammatory reactions, a feature that allows modulation by therapeutic treatments. In the present review, we describe and discuss the effects of extremely low frequency (ELF)-EMF and pulsed EMF on cell signals and factors relevant to the activation of danger signals and innate immunity cells. By discussing the EMF modulating effects on cell functions, we envisage the use of EMF as a therapeutic agent to regulate immune responses associated with wound healing.

Immune oncology, immune responsiveness and the theory of everything.

PubMed

Turan, Tolga; Kannan, Deepti; Patel, Maulik; Matthew Barnes, J; Tanlimco, Sonia G; Lu, Rongze; Halliwill, Kyle; Kongpachith, Sarah; Kline, Douglas E; Hendrickx, Wouter; Cesano, Alessandra; Butterfield, Lisa H; Kaufman, Howard L; Hudson, Thomas J; Bedognetti, Davide; Marincola, Francesco; Samayoa, Josue

2018-06-05

Anti-cancer immunotherapy is encountering its own checkpoint. Responses are dramatic and long lasting but occur in a subset of tumors and are largely dependent upon the pre-existing immune contexture of individual cancers. Available data suggest that three landscapes best define the cancer microenvironment: immune-active, immune-deserted and immune-excluded. This trichotomy is observable across most solid tumors (although the frequency of each landscape varies depending on tumor tissue of origin) and is associated with cancer prognosis and response to checkpoint inhibitor therapy (CIT). Various gene signatures (e.g. Immunological Constant of Rejection - ICR and Tumor Inflammation Signature - TIS) that delineate these landscapes have been described by different groups. In an effort to explain the mechanisms of cancer immune responsiveness or resistance to CIT, several models have been proposed that are loosely associated with the three landscapes. Here, we propose a strategy to integrate compelling data from various paradigms into a "Theory of Everything". Founded upon this unified theory, we also propose the creation of a task force led by the Society for Immunotherapy of Cancer (SITC) aimed at systematically addressing salient questions relevant to cancer immune responsiveness and immune evasion. This multidisciplinary effort will encompass aspects of genetics, tumor cell biology, and immunology that are pertinent to the understanding of this multifaceted problem.

[Plant immune system: the basal immunity].

PubMed

Shamraĭ, S N

2014-01-01

Plants have an efficient system of innate immunity which is based on the effective detection of potentially harmful microorganisms and rapid induction of defense responses. The first level of plant immunity is the basal immunity which is induced by the conserved molecular structures of microbes such as bacterial flagellins or fungal chitin, or molecules that result from the interaction of plants with pathogens, for example oligosaccharides and peptides ("danger signals"). Plants recognize these inducers through receptors localized to the plasma membrane, represented mainly receptor-like protein kinases or receptor-like proteins. Activation of the receptor by a ligand triggers a complex network of signaling events which eventually cause an array of plant defense responses to prevent further spread of the pathogen.

DNA Immunization

PubMed Central

Wang, Shixia; Lu, Shan

2013-01-01

DNA immunization was discovered in early 1990s and its use has been expanded from vaccine studies to a broader range of biomedical research, such as the generation of high quality polyclonal and monoclonal antibodies as research reagents. In this unit, three common DNA immunization methods are described: needle injection, electroporation and gene gun. In addition, several common considerations related to DNA immunization are discussed. PMID:24510291

Temperature-responsive release of cortisol from its binding globulin: a protein thermocouple.

PubMed

Cameron, Angus; Henley, David; Carrell, Robin; Zhou, Aiwu; Clarke, Anthony; Lightman, Stafford

2010-10-01

Only 5% of circulating cortisol is active and unbound to carrier proteins. Because cortisol levels vary rapidly due to the pulsatile nature of cortisol secretion, the dynamics of cortisol binding are critical determinants of tissue levels of free cortisol and consequent hormonal signaling. The major glucocorticoid carrier protein is corticosteroid binding globulin (CBG), a member of the serpin family that undergoes conformational changes to bind and release hormones. This mechanism has been noted to be temperature responsive, and we have now investigated the effects of temperature on the binding of human CBG to both cortisol and progesterone. Recombinant human CBG was synthesized and used for binding studies with cortisol and progesterone between 34 and 43 C. Binding was monitored by recording the change in intrinsic protein fluorescence. Binding of the steroids to the other major carrier, serum albumin, was measured in a similar manner. There was no effect of temperature on the interaction between human serum albumin and either cortisol or progesterone. The association of both cortisol and progesterone with CBG is more than three orders of magnitude greater than that with HSA, and this interaction was extremely responsive to changes in temperature. The affinity of both cortisol and progesterone for CBG drops approximately 16-fold as temperature increases from 35 to 42 C. This study clearly shows that even within the clinically relevant range of temperatures found in humans, CBG acts as a protein thermocouple that is exquisitely sensitive to temperature change and will release cortisol in response to fever or external sources of heat. This has major implications for our understanding of cortisol regulation in febrile patients.

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

PubMed

Sheikh, Ishfaq A; Beg, Mohd A

2017-12-01

Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

Immunization in pregnancy.

PubMed

Gruslin, Andrée; Steben, Marc; Halperin, Scott; Money, Deborah M; Yudin, Mark H; Boucher, Marc; Cormier, Beatrice; Ogilvie, Gina; Paquet, Caroline; Steenbeek, Audrey; Van Eyk, Nancy; van Schalkwyk, Julie; Wong, Thomas

2008-12-01

To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization, and risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to June 2007 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. Recommendations 1. All women of childbearing age should be evaluated for the possibility of pregnancy before immunization. (III-A) 2. Health care providers should obtain an immunization history from all women accessing prenatal care. (III-A) 3. In general, live and/or live-attenuated virus vaccines are contraindicated during pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3) 4. Women who have inadvertently received immunization with live or live-attenuated vaccines during pregnancy should not be counselled to terminate the pregnancy because of a teratogenic risk. (II-2) 5. Non-pregnant women immunized with a live or live-attenuated vaccine should be counselled to delay pregnancy for at least four weeks. (III) 6. Inactivated viral vaccines, bacterial vaccines, and toxoids are considered safe in pregnancy. (II-1) 7. Women who are breastfeeding can still be immunized (passive-active immunization, live or killed vaccines). (II-1) 8. Pregnant women should be offered the influenza vaccine when pregnant during the influenza season. (II-1).

Immunization Action Coalition

MedlinePlus

... Email CDC: nipinfo@cdc.gov Contact: State Immunization Managers Email IAC: admin@immunize.org This page was ... STATE INFORMATION State Websites State Laws State Immunization Managers >> view all SUBSCRIBE SUPPORT IAC TECHNICALLY SPEAKING TRANSLATE ...

Evaluation of health status of horses immunized with snake venom and montanide adjuvants, IMS 3012 (nanoparticle), ISA 206 and ISA 35 (emulsion based) during polyvalent snake antivenom production: hematological and biochemical assessment.

PubMed

Waghmare, A B; Salvi, N C; Deopurkar, R L; Shenoy, P A; Sonpetkar, J M

2014-05-01

Several biochemical and hematological changes in horses are observed during production of snake antivenom. Although conventional adjuvants like Freund's (Complete and Incomplete) are good immunopotentiators, they produce considerable local reactions in animals. Variety of commercial adjuvants, like montanide adjuvants, having high immunopotentiation and showing lesser side effects are available. The prime objective during antivenom production is to strike a balance between safety of immunized horses and efficacy of the product. In our earlier work, efficacy of montanide group of adjuvants in antivenom production has already been established. The aim of the present work was to assess the safety parameters in horses, viz.: biochemical and hematological, during production of snake antivenom. In the present study, 33 new horses were randomly divided into four groups and hyperimmunized using mixture of snake venoms, viz.: Cobra venom, Russell's viper venom, Krait venom and Echis venom along with montanide adjuvants, IMS 3012, ISA 206, ISA 35 and Incomplete Freund's adjuvant as a control adjuvant; through subcutaneous route at intervals of two weeks. During the immunization period, biochemical and hematological parameters were monitored at 0th, 14th, 21st, 30th and 42nd weeks. The mean hemoglobin values dropped slightly during initial immunization but subsequently regained to normal levels. The mean serum total protein values and globulin levels showed an increment in all the four groups, compared to day zero, vice-versa a slight drop was observed in albumin levels. No significant changes were observed in serum creatinine, bilirubin, alkaline phosphatase and blood urea nitrogen values. Finally, we conclude that montanide adjuvants could be a safer alternative to the conventional adjuvants for primary phase of immunization in antivenom production. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of treatment with probiotics as water additives on tilapia (Oreochromis niloticus) growth performance and immune response.

PubMed

Zhou, Xuxia; Tian, Ziqiang; Wang, Yanbo; Li, Weifen

2010-09-01

A feeding trial was conducted for 40 days to delineate the effect of treatment with probiotics as water additives on tilapia (Oreochromis niloticus) growth performance and immune response. About 360 juveniles were randomly distributed into four treatment groups, each with three replicates. Different probiotics (T-1, Bacillus subtilis B10; T-2, Bacillus coagulans B16; T-3, Rhodopseudomonas palustris G06) were added to the water of tanks at final concentration of 1 x 10(7) cfu ml(-1) every 2 days, with no probiotic added to control tanks. At the end of the feeding trial, fish treated with B. coagulans B16 (T-2) and R. palustris G06 (T-3) had significantly (P < 0.05) higher final weight, daily weight gain, and specific growth rate compared with those treated with B. subtilis B10 (T-1) and those without probiotics (control). The highest (P < 0.05) content of total serum protein was found in T-2 compared with that in T-1, T-3, and the control. However, albumin concentration and albumin/globulin ratio were not affected by the probiotics treatments. Compared with the control, probiotic supplementation remarkably improved activities of superoxide dismutase and catalase (P < 0.05). T-2 fish exhibited higher average myeloperoxidase activity than the control, T-1, and T-3 groups. Regarding serum lysozyme content in tilapia, assays showed no difference (P > 0.05) among the treatment groups. Furthermore, probiotics treatments remarkably increased respiratory burst activity compared with control, with T-2 showing higher values than T-1 and T-3. This indicated that treatment with probiotics, B. coagulans B16 and R. palustris G06, as water additives could be used to enhance immune and health status, thereby improving growth performance of O. niloticus.

Immune System Quiz

MedlinePlus

... Videos for Educators Search English Español Quiz: Immune System KidsHealth / For Kids / Quiz: Immune System Print How much do you know about your immune system? Find out by taking this quiz! About Us ...

Assessing barriers to immunization.

PubMed

Niederhauser, Victoria; Ferris, Catherine

2016-05-03

Parental barriers to childhood immunizations vary among countries, states and communities. There is a plethora of studies that exist to examine barriers to immunizations including many intervention studies designed to improve immunization rates in children. Often, intervention studies designed to minimize barriers and increase immunization uptake among children lack the inclusion of a standardized instrument to measure accurately parental barriers to childhood immunizations before and after interventions. The Searching for Hardships and Obstacles To Shots (SHOTS) survey is a standardized survey instrument to measure parental barriers to childhood immunizations. In several studies, the SHOTS survey has demonstrated consistent reliability and has been validated in diverse populations. The inclusion of the SHOTS survey instrument in studies to examine barriers to childhood immunization will provide researchers and clinicians with a better understanding of parents' individualized barriers to immunizations. Furthermore, use of the SHOTS survey instrument to collect information about parental barriers to immunizations can lead to targeted interventions to minimize these obstacles at the individual and community level and to help us to achieve our national, state and community childhood immunization goals.

Immune Receptors and Co-receptors in Antiviral Innate Immunity in Plants.

PubMed

Gouveia, Bianca C; Calil, Iara P; Machado, João Paulo B; Santos, Anésia A; Fontes, Elizabeth P B

2016-01-01

Plants respond to pathogens using an innate immune system that is broadly divided into PTI (pathogen-associated molecular pattern- or PAMP-triggered immunity) and ETI (effector-triggered immunity). PTI is activated upon perception of PAMPs, conserved motifs derived from pathogens, by surface membrane-anchored pattern recognition receptors (PRRs). To overcome this first line of defense, pathogens release into plant cells effectors that inhibit PTI and activate effector-triggered susceptibility (ETS). Counteracting this virulence strategy, plant cells synthesize intracellular resistance (R) proteins, which specifically recognize pathogen effectors or avirulence (Avr) factors and activate ETI. These coevolving pathogen virulence strategies and plant resistance mechanisms illustrate evolutionary arms race between pathogen and host, which is integrated into the zigzag model of plant innate immunity. Although antiviral immune concepts have been initially excluded from the zigzag model, recent studies have provided several lines of evidence substantiating the notion that plants deploy the innate immune system to fight viruses in a manner similar to that used for non-viral pathogens. First, most R proteins against viruses so far characterized share structural similarity with antibacterial and antifungal R gene products and elicit typical ETI-based immune responses. Second, virus-derived PAMPs may activate PTI-like responses through immune co-receptors of plant PTI. Finally, and even more compelling, a viral Avr factor that triggers ETI in resistant genotypes has recently been shown to act as a suppressor of PTI, integrating plant viruses into the co-evolutionary model of host-pathogen interactions, the zigzag model. In this review, we summarize these important progresses, focusing on the potential significance of antiviral immune receptors and co-receptors in plant antiviral innate immunity. In light of the innate immune system, we also discuss a newly uncovered layer of

Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

PubMed

Peng, Yujun; van Wersch, Rowan; Zhang, Yuelin

2018-04-01

Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

[The effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mother].

PubMed

Kong, H H; Seo, S A; Shin, C O; Im, K I

1993-06-01

Acanthamoeba culbertsoni is a pathogenic free-living amoeba causing primary amoebic meningoencephalitis (PAME) in human and mouse. Several reports on the immune responses in mice with this amoebic infection have been published, but the effects of transferred passive immunity on the active immunization in offspring mice have not been demonstrated. This experiment was done to observe the effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mothers. Acanthamoeba culbertsoni was cultured in the CGV medium axenically. Female BALB/c mice weighing about 20g were immunized through the intraperitoneal injection of Acanthamoeba culbertsoni trophozoites 1 x 10(6) each three times at the interval of one week. Offspring mice were immunized two times. The mice were inoculated intranasally with 1 x 10(4) trophozoites under secobarbital anesthesia. There was a statistical difference in mortality between the transferred immunity group and the active immunization group. Statistical differences were not demonstrated in antibody titer between both groups. But L3T4+ T cell/Ly2+ T cell ratio was increased in the transferred immunity group more than active immunization group of the offspring mice at the age of 5 weeks. There was no differences statistically in mortality between both groups. It was recognized that active immunization in offspring mice born to immune mother could modulate the immune status according to the time of immunization.

Statistical Approach To Estimate Vaccinia-Specific Neutralizing Antibody Titers Using a High-Throughput Assay▿

PubMed Central

Kennedy, Richard; Pankratz, V. Shane; Swanson, Eric; Watson, David; Golding, Hana; Poland, Gregory A.

2009-01-01

Because of the bioterrorism threat posed by agents such as variola virus, considerable time, resources, and effort have been devoted to biodefense preparation. One avenue of this research has been the development of rapid, sensitive, high-throughput assays to validate immune responses to poxviruses. Here we describe the adaptation of a β-galactosidase reporter-based vaccinia virus neutralization assay to large-scale use in a study that included over 1,000 subjects. We also describe the statistical methods involved in analyzing the large quantity of data generated. The assay and its associated methods should prove useful tools in monitoring immune responses to next-generation smallpox vaccines, studying poxvirus immunity, and evaluating therapeutic agents such as vaccinia virus immune globulin. PMID:19535540

Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B.

PubMed

Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Harrison, Linda; Decker, Luc; Khamduang, Woottichai; Tierney, Camlin; Salvadori, Nicolas; Cressey, Tim R; Sirirungsi, Wasna; Achalapong, Jullapong; Yuthavisuthi, Prapap; Kanjanavikai, Prateep; Na Ayudhaya, Orada P; Siriwachirachai, Thitiporn; Prommas, Sinart; Sabsanong, Prapan; Limtrakul, Aram; Varadisai, Supang; Putiyanun, Chaiwat; Suriyachai, Pornnapa; Liampongsabuddhi, Prateung; Sangsawang, Suraphan; Matanasarawut, Wanmanee; Buranabanjasatean, Sudanee; Puernngooluerm, Pichit; Bowonwatanuwong, Chureeratana; Puthanakit, Thanyawee; Klinbuayaem, Virat; Thongsawat, Satawat; Thanprasertsuk, Sombat; Siberry, George K; Watts, Diane H; Chakhtoura, Nahida; Murphy, Trudy V; Nelson, Noele P; Chung, Raymond T; Pol, Stanislas; Chotivanich, Nantasak

2018-03-08

Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants' receiving hepatitis B immune globulin. In this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)-positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 weeks of gestation to 2 months post partum. Infants received hepatitis B immune globulin at birth and hepatitis B vaccine at birth and at 1, 2, 4, and 6 months. The primary end point was a hepatitis B surface antigen (HBsAg)-positive status in the infant, confirmed by the HBV DNA level at 6 months of age. We calculated that a sample of 328 women would provide the trial with 90% power to detect a difference of at least 9 percentage points in the transmission rate (expected rate, 3% in the TDF group vs. 12% in the placebo group). From January 2013 to August 2015, we enrolled 331 women; 168 women were randomly assigned to the TDF group and 163 to the placebo group. At enrollment, the median gestational age was 28.3 weeks, and the median HBV DNA level was 8.0 log 10 IU per milliliter. Among 322 deliveries (97% of the participants), there were 319 singleton births, two twin pairs, and one stillborn infant. The median time from birth to administration of hepatitis B immune globulin was 1.3 hours, and the median time from birth to administration of hepatitis B vaccine was 1.2 hours. In the primary analysis, none of the 147 infants (0%; 95% confidence interval [CI], 0 to 2) in the TDF group were infected, as compared with 3 of 147 (2%; 95% CI, 0 to 6) in the placebo group (P=0.12). The rate of adverse events did not differ significantly between groups. The incidence of a maternal alanine aminotransferase level of more than 300 IU per liter after discontinuation of the trial regimen was 6% in the TDF group and 3% in

Nucleic Acid Immunity.

PubMed

Hartmann, G

2017-01-01

Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity. With inherited receptors and acquired sequence information, nucleic acid immunity comprises innate and adaptive components. Effector functions include diverse nuclease systems, intrinsic activities to directly restrict the function of foreign nucleic acids (e.g., PKR, ADAR1, IFIT1), and extrinsic pathways to alert the immune system and to elicit cytotoxic immune responses. These effects act in concert to restrict viral replication and to eliminate virus-infected cells. The principles of nucleic acid immunity are highly relevant for human disease. Besides its essential contribution to antiviral defense and restriction of endogenous retroelements, dysregulation of nucleic acid immunity can also lead to erroneous detection and response to self nucleic acids then causing sterile inflammation and autoimmunity. Even mechanisms of nucleic acid immunity which are not established in vertebrates are relevant for human disease when they are present in pathogens such as bacteria, parasites, or helminths or in pathogen-transmitting organisms such as insects. This review aims to provide an overview of the diverse mechanisms of nucleic acid immunity which mostly have been looked at separately in the past and to integrate them under the framework nucleic acid immunity as a basic principle of life, the understanding of which has great potential to

Mucosal Vaccination Overcomes the Barrier to Recombinant Vaccinia Immunization Caused by Preexisting Poxvirus Immunity

NASA Astrophysics Data System (ADS)

Belyakov, Igor M.; Moss, Bernard; Strober, Warren; Berzofsky, Jay A.

1999-04-01

Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.

[Immune system and tumors].

PubMed

Terme, Magali; Tanchot, Corinne

2017-02-01

Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

CMV immune evasion and manipulation of the immune system with aging.

PubMed

Jackson, Sarah E; Redeker, Anke; Arens, Ramon; van Baarle, Debbie; van den Berg, Sara P H; Benedict, Chris A; Čičin-Šain, Luka; Hill, Ann B; Wills, Mark R

2017-06-01

Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response. Without reactivation, latency itself would be redundant for the virus. It is also becoming clear that latency is not a totally quiescent state, but is characterized by limited viral gene expression. Therefore, the virus also needs immune evasion strategies during latency. An effective immune response to CMV is required or viral replication will cause morbidity and ultimately mortality in the host. There is clearly a complex balance between virus immune evasion and host immune recognition over a lifetime. This poses the important question of whether long-term evasion or manipulation of the immune response driven by CMV is detrimental to health. In this meeting report, three groups used the murine model of CMV (MCMV) to examine if the contribution of the virus to immune senescence is set by the (i) initial viral inoculum, (ii) inflation of T cell responses, (iii) or the balance between functionally distinct effector CD4+ T cells. The work of other groups studying the CMV response in humans is discussed. Their work asks whether the ability to make immune responses to new antigens is compromised by (i) age and HCMV carriage, (ii) long-term exposure to HCMV giving rise to an overall immunosuppressive environment and increased levels of latent virus, or (iii) adapted virus mutants (used as potential vaccines) that have the capacity to

Immunization Schedule

MedlinePlus

... third dose may be needed, depending on the brand of vaccine used in previous Hib immunizations. PCV ... third dose may be needed, depending on the brand of vaccine used in previous RV immunizations. 6 ...

Impact of Pharmacist Immunization Authority on Seasonal Influenza Immunization Rates Across States.

PubMed

Drozd, Edward M; Miller, Laura; Johnsrud, Michael

2017-08-01

The goal of this study was to investigate the impact on immunization rates of policy changes that allowed pharmacists to administer influenza immunizations across the United States. Influenza immunization rates across states were compared before and after policy changes permitting pharmacists to administer influenza immunizations. The study used Behavioral Risk Factor Surveillance System (BRFSS) survey data on influenza immunization rates between 2003 and 2013. Logistic regression models were constructed and incorporated adjustments for the complex sample design of the BRFSS to predict the likelihood of a person receiving an influenza immunization based on various patient health, demographic, and access to care factors. Overall, as states moved to allow pharmacists to administer influenza immunizations, the odds that an adult resident received an influenza immunization rose, with the effect increasing over time. The average percentage of people receiving influenza immunizations in states was 35.1%, rising from 32.2% in 2003 to 40.3% in 2013. The policy changes were associated with a long-term increase of 2.2% to 7.6% in the number of adults aged 25 to 59 years receiving an influenza immunization (largest for those aged 35-39 years) and no significant change for those younger or older. These findings suggest that pharmacies and other nontraditional settings may offer accessible venues for patients when implementing other public health initiatives. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Serum corticosteroid binding globulin expression is modulated by fasting in polar bears (Ursus maritimus).

PubMed

Chow, Brian A; Hamilton, Jason; Cattet, Marc R L; Stenhouse, Gordon; Obbard, Martyn E; Vijayan, Mathilakath M

2011-01-01

Polar bears (Ursus maritimus) from several subpopulations undergo extended fasting during the ice-free season. However, the animals appear to conserve protein despite the prolonged fasting, though the mechanisms involved are poorly understood. We hypothesized that elevated concentrations of corticosteroid binding globulin (CBG), the primary cortisol binding protein in circulation, lead to cortisol resistance and provide a mechanism for protein conservation during extended fasting. The metabolic state (feeding vs. fasting) of 16 field sampled male polar bears was determined based on their serum urea to creatinine ratio (>25 for feeding vs. <5 for fasting). There were no significant differences in serum cortisol levels between all male and female polar bears sampled. Serum CBG expression was greater in lactating females relative to non-lactating females and males. CBG expression was significantly higher in fasting males when compared to non-fasting males. This leads us to suggest that CBG expression may serve as a mechanism to conserve protein during extended fasting in polar bears by reducing systemic free cortisol concentrations. This was further supported by a lower serum glucose concentration in the fasting bears. As well, a lack of an enhanced adrenocortical response to acute capture stress supports our hypothesis that chronic hunger is not a stressor in this species. Overall, our results suggest that elevated serum CBG expression may be an important adaptation to spare proteins by limiting cortisol bioavailability during extended fasting in polar bears. Copyright © 2010 Elsevier Inc. All rights reserved.

In silico identification of anthropogenic chemicals as ligands of zebrafish sex hormone binding globulin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thorsteinson, Nels; Ban, Fuqiang; Santos-Filho, Osvaldo

2009-01-01

Anthropogenic compounds with the capacity to interact with the steroid-binding site of sex hormone binding globulin (SHBG) pose health risks to humans and other vertebrates including fish. Building on studies of human SHBG, we have applied in silico drug discovery methods to identify potential binders for SHBG in zebrafish (Danio rerio) as a model aquatic organism. Computational methods, including; homology modeling, molecular dynamics simulations, virtual screening, and 3D QSAR analysis, successfully identified 6 non-steroidal substances from the ZINC chemical database that bind to zebrafish SHBG (zfSHBG) with low-micromolar to nanomolar affinities, as determined by a competitive ligand-binding assay. We alsomore » screened 80,000 commercial substances listed by the European Chemicals Bureau and Environment Canada, and 6 non-steroidal hits from this in silico screen were tested experimentally for zfSHBG binding. All 6 of these compounds displaced the [{sup 3}H]5{alpha}-dihydrotestosterone used as labeled ligand in the zfSHBG screening assay when tested at a 33 {mu}M concentration, and 3 of them (hexestrol, 4-tert-octylcatechol, and dihydrobenzo(a)pyren-7(8H)-one) bind to zfSHBG in the micromolar range. The study demonstrates the feasibility of large-scale in silico screening of anthropogenic compounds that may disrupt or highjack functionally important protein:ligand interactions. Such studies could increase the awareness of hazards posed by existing commercial chemicals at relatively low cost.« less

Effect of maternal immunization with oral poliovirus vaccine on neonatal immunity.

PubMed

Linder, N; Handsher, R; Fruman, O; Shiff, E; Ohel, G; Reichman, B; Dagan, R

1994-11-01

During the summer of 1988, an outbreak of poliomyelitis caused by poliovirus 1 occurred in Israel, during which a national mass immunization campaign with oral poliovirus was undertaken. This prospective study was undertaken to assess the effect of maternal oral poliovirus immunization during the third trimester of pregnancy on neonatal immunity against poliovirus. Cord blood specimens of 88 neonates, born 2 to 7 weeks after maternal immunization, were examined for antipoliovirus antibodies and compared with 100 samples obtained from neonates 7 months before the outbreak. Blood samples were also obtained from the 62 mothers of neonates who had been immunized 2 to 5 weeks before delivery. Sera were tested for neutralizing antibodies to the 3 poliovirus types using a microneutralization technique. The geometric mean titer to poliovirus type 1 was significantly higher in neonates whose mothers were immunized during pregnancy (87.1) than in the offspring of the nonvaccinated group (53.0), P < 0.05. Two to 3 weeks after immunization, geometric mean titers against all 3 poliovirus types were higher in maternal blood than in cord blood whereas 4 to 5 weeks after vaccination a significant difference was found for type 3 only. Although oral poliovirus immunization during pregnancy resulted in higher neonatal antibody titers to poliovirus type 1, the proportion of newborns with titers of < 1:8 to the 3 poliovirus types did not change significantly.

Antithymocyte globulins in renal transplantation-from lymphocyte depletion to lymphocyte activation: The doubled-edged sword.

PubMed

Bamoulid, Jamal; Crépin, Thomas; Courivaud, Cécile; Rebibou, Jean-Michel; Saas, Philippe; Ducloux, Didier

2017-07-01

Compelling data suggest that lymphocyte depletion following T cell depleting therapy may induce prolonged CD4 T cell lymphopenia and trigger lymphocyte activation in some patients. These profound and non-reversible immune changes in T cell pool subsets are the consequence of both impaired thymic renewal and peripheral homeostatic proliferation. Chronic viral challenges by CMV play a major role in these immune alterations. Even when the consequences of CD4 T cell lymphopenia have been now well described, recent studies shed new light on the clinical consequences of immune activation. In this review, we will first focus on the mechanisms involved in T cell pool reconstitution after T cell depletion and further consider the clinical consequences of ATG-induced T cell activation and senescence in renal transplant recipients. Copyright © 2017 Elsevier Inc. All rights reserved.

Induction of protective immunity against toxoplasmosis in mice by immunization with Toxoplasma gondii RNA.

PubMed

Dimier-Poisson, Isabelle; Aline, Fleur; Bout, Daniel; Mévélec, Marie-Noëlle

2006-03-06

Toxoplasma gondii enters the mucosal surfaces of the host, and so immunity at these sites is of major interest. Due to the compartmentalization of the immune response, systemic immunization does not induce high levels of immunity at mucosal surfaces. Intranasal immunization has been shown to be very effective in inducing both systemic and mucosal immune responses. Immunization with mRNA can induce both humoral and cell-mediated immune responses, both of which are important in conferring immunity to T. gondii. The efficacy of RNA vaccination by the nasal route with T. gondii RNA was evaluated. We assessed the percentage of cumulative survival after an oral challenge with a lethal dose of T. gondii cysts (40 cysts), and the number of brain cysts following a challenge with a sublethal dose of T. gondii 76 K cysts (15 cysts). Vaccinated mice were found to be significantly better protected than non-immunized mice after a challenge with a lethal dose of cysts; and a challenge with a sublethal dose also resulted in fewer brain cysts than in non-immunized mice. Sera and intestinal secretions of immunized mice recognized T. gondii antigens, suggesting that a specific humoral immune response may occur. Moreover, a specific lymphoproliferative response observed in cervical lymph nodes may confer protection. These preliminary findings suggest that RNA vaccination by a mucosal route could be feasible.

Immunization coverage among Hispanic ancestry, 2003 National Immunization Survey.

PubMed

Darling, Natalie J; Barker, Lawrence E; Shefer, Abigail M; Chu, Susan Y

2005-12-01

The Hispanic population is increasing and heterogeneous (Hispanic refers to persons of Spanish, Hispanic, or Latino descent). The objective was to examine immunization rates among Hispanic ancestry for the 4:3:1:3:3 series (> or = 4 doses diphtheria, tetanus toxoids, and pertussis vaccine; > or = 3 doses poliovirus vaccine; > or = 1 doses measles-containing vaccine; > or = 3 doses Haemophilus influenzae type b vaccine; and > or = 3 doses hepatitis B vaccine). The National Immunization Survey measures immunization coverage among 19- to 35-month-old U.S. children. Coverage was compared from combined 2001-2003 data among Hispanics and non-Hispanic whites using t-tests, and among Hispanic ancestry using a chi-square test. Hispanics were categorized as Mexican, Mexican American, Central American, South American, Puerto Rican, Cuban, Spanish Caribbean (primarily Dominican Republic), other, and multiple ancestry. Children of Hispanic ancestry increased from 21% in 1999 to 25% in 2003. These Hispanic children were less well immunized than non-Hispanic whites (77.0%, +/-2.1% [95% confidence interval] compared to 82.5%, +/-1.1% (95% CI) > in 2003). Immunization coverage did not vary significantly among Hispanics of varying ancestries (p=0.26); however, there was substantial geographic variability. In some areas, immunization coverage among Hispanics was significantly higher than non-Hispanic whites. Hispanic children were less well immunized than non-Hispanic whites; however, coverage varied notably by geographic area. Although a chi-square test found no significant differences in coverage among Hispanic ancestries, the range of coverage, 79.2%, +/-5.1% for Cuban Americans to 72.1%, +/-2.4% for Mexican descent, may suggest a need for improved and more localized monitoring among Hispanic communities.

Mesenchymal stem cells: immune evasive, not immune privileged

PubMed Central

Ankrum, James A.; Ong, Joon Faii; Karp, Jeffrey M.

2014-01-01

The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) may be exploited for treatment of a multitude of inflammatory conditions. MSCs have long been reported to be hypoimmunogenic or ‘immune privileged’; this property is thought to enable MSC transplantation across major histocompatibility barriers and the creation of off-the-shelf therapies consisting of MSCs grown in culture. However, recent studies describing generation of antibodies against and immune rejection of allogeneic donor MSCs suggest that MSCs may not actually be immune privileged. Nevertheless, whether rejection of donor MSCs influences the efficacy of allogeneic MSC therapies is not known, and no definitive clinical advantage of autologous MSCs over allogeneic MSCs has been demonstrated to date. Although MSCs may exert therapeutic function through a brief ‘hit and run’ mechanism, protecting MSCs from immune detection and prolonging their persistence in vivo may improve clinical outcomes and prevent patient sensitization toward donor antigens. PMID:24561556

Plant immunity against viruses: antiviral immune receptors in focus

PubMed Central

Calil, Iara P.

2017-01-01

Abstract Background Among the environmental limitations that affect plant growth, viruses cause major crop losses worldwide and represent serious threats to food security. Significant advances in the field of plant–virus interactions have led to an expansion of potential strategies for genetically engineered resistance in crops during recent years. Nevertheless, the evolution of viral virulence represents a constant challenge in agriculture that has led to a continuing interest in the molecular mechanisms of plant–virus interactions that affect disease or resistance. Scope and Conclusion This review summarizes the molecular mechanisms of the antiviral immune system in plants and the latest breakthroughs reported in plant defence against viruses. Particular attention is given to the immune receptors and transduction pathways in antiviral innate immunity. Plants counteract viral infection with a sophisticated innate immune system that resembles the non-viral pathogenic system, which is broadly divided into pathogen-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity. An additional recently uncovered virus-specific defence mechanism relies on host translation suppression mediated by a transmembrane immune receptor. In all cases, the recognition of the virus by the plant during infection is central for the activation of these innate defences, and, conversely, the detection of host plants enables the virus to activate virulence strategies. Plants also circumvent viral infection through RNA interference mechanisms by utilizing small RNAs, which are often suppressed by co-evolving virus suppressors. Additionally, plants defend themselves against viruses through hormone-mediated defences and activation of the ubiquitin–26S proteasome system (UPS), which alternatively impairs and facilitates viral infection. Therefore, plant defence and virulence strategies co-evolve and co-exist; hence, disease development is largely dependent on

Plant immunity against viruses: antiviral immune receptors in focus.

PubMed

Calil, Iara P; Fontes, Elizabeth P B

2017-03-01

Among the environmental limitations that affect plant growth, viruses cause major crop losses worldwide and represent serious threats to food security. Significant advances in the field of plant-virus interactions have led to an expansion of potential strategies for genetically engineered resistance in crops during recent years. Nevertheless, the evolution of viral virulence represents a constant challenge in agriculture that has led to a continuing interest in the molecular mechanisms of plant-virus interactions that affect disease or resistance. This review summarizes the molecular mechanisms of the antiviral immune system in plants and the latest breakthroughs reported in plant defence against viruses. Particular attention is given to the immune receptors and transduction pathways in antiviral innate immunity. Plants counteract viral infection with a sophisticated innate immune system that resembles the non-viral pathogenic system, which is broadly divided into pathogen-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity. An additional recently uncovered virus-specific defence mechanism relies on host translation suppression mediated by a transmembrane immune receptor. In all cases, the recognition of the virus by the plant during infection is central for the activation of these innate defences, and, conversely, the detection of host plants enables the virus to activate virulence strategies. Plants also circumvent viral infection through RNA interference mechanisms by utilizing small RNAs, which are often suppressed by co-evolving virus suppressors. Additionally, plants defend themselves against viruses through hormone-mediated defences and activation of the ubiquitin-26S proteasome system (UPS), which alternatively impairs and facilitates viral infection. Therefore, plant defence and virulence strategies co-evolve and co-exist; hence, disease development is largely dependent on the extent and rate at which these opposing

Chapter 2: Innate Immunity

PubMed Central

Turvey, Stuart E.; Broide, David H.

2009-01-01

Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease. PMID:19932920

Immunization in pregnancy.

PubMed

Gruslin, Andrée; Steben, Marc; Halperin, Scott; Money, Deborah M; Yudin, Mark H

2009-11-01

To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization, risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to June 2008 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. The quality of evidence reported in this document has been assessed using the evaluation of evidence criteria in the Report of the Canadian Task Force on Preventive Health Care (Table 1). (1) All women of childbearing age should be evaluated for the possibility of pregnancy before immunization. (III-A). (2) Health care providers should obtain a relevant immunization history from all women accessing prenatal care. (III-A). (3) In general, live and/or live-attenuated virus vaccines should not be administered during pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3B). (4) Women who have inadvertently received immunization with live or live-attenuated vaccines during pregnancy should not be counselled to terminate the pregnancy because of a teratogenic risk. (II-2A). (5) Non-pregnant women immunized with a live or live-attenuated vaccine should be counselled to delay pregnancy for at least four weeks. (III-B). (6) Inactivated viral vaccines, bacterial vaccines, and toxoids can be used safely in pregnancy. (II-1A). (7) Women who are breastfeeding can still be immunized (passive-active immunization, live or killed

The Immune System: Basis of so much Health and Disease: 2. Innate Immunity.

PubMed

Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

2017-03-01

The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system, this article covering innate immunity. Clinical relevance: Modern dental clinicians need a basic understanding of the immune system as it underlies health and disease.

The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.

PubMed

Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

2017-04-01

The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system; this article covers adaptive immunity. Clinical relevance: Dental clinicians need a basic understanding of the immune system as it underlies health and disease.

Immunohistochemical analysis of cytokeratin and human milk fat globulin expression in mucinous carcinoma of the skin.

PubMed

Ohnishi, Takamitsu; Takizawa, Hajime; Watanabe, Shinichi

2002-01-01

Mucinous carcinoma of the skin (MCS) is a rare epithelial tumor which arises primarily in the skin. Metastatic MC from extracutaneous sites, especially breast or colon, mimics MCS and cannot be differentiated from MCS by routine histology alone. Nine cases of MCS were analyzed immunohistochemically using monoclonal antibodies against cytokeratins (CKs) and human milk fat globulin 1 (HMFG) in order to clarify their nature and compare the immunophenotypes with those of other MCs studied in the literature. Expression of simple epithelial CKs in most of the tumor cells of all cases studied and co-expression of simple and stratified epithelial CKs in some tumor cells of two cases were recognized. CK 20 expression could not detected in any tumor cells. Focal HMFG expression in the luminal or outer surface of the nests was observed in three cases. From CKs expression, MCS was speculated to differentiated mainly toward the secretory cells of the sweat glands, and some tumor cells toward the transient portion between the dermal duct and the secretory portion. Focal HMFG expression suggested either a consequence of malignant transformation or apocrine differentiation. No expression of CK 20 in MCS suggests that we may exclude the diagnosis of metastatic colorectal MC which expressed CK 20.

Genetic variants determining body fat distribution and sex hormone-binding globulin among Chinese female young adults.

PubMed

Shi, Juan; Li, Lijuan; Hong, Jie; Qi, Lu; Cui, Bin; Gu, Weiqiong; Zhang, Yifei; Miao, Lin; Wang, Rui; Wang, Weiqing; Ning, Guang

2014-11-01

Measures of body fat distribution (i.e. waist : hip ratio [WHR]) are major risk factors for diabetes, independent of overall adiposity. The genetic variants related to body fat distribution show sexual dimorphism and particularly affect females. Substantial literature supports a role for sex hormone-binding globulin (SHBG) in the maintenance of glucose homeostasis. The aim of the present study was to examine the association of the genetic risk score of body fat distribution with SHBG levels and insulin resistance in young (14-30 years) Chinese females. In all, 675 young Chinese females were evaluated in the present study. A genetic risk score (GRS) was calculated on the basis of 12 established variants associated with body fat distribution. The main outcome variable was serum SHBG levels and homeostasis model assessment of insulin resistance (HOMA-IR). The GRS of body fat distribution was significantly associated with decreasing serum SHBG levels (P = 0.018), independent of body mass index and WHR. In addition, the GRS and SHBG showed additive effects on HOMA-IR (P = 0.004). The GRS of body fat distribution reflects serum SHBG levels, and the GRS and SHBG jointly influence the risk of insulin resistance. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Pericarditis mediated by respiratory syncytial virus in a hematopoietic stem cell transplant patient.

PubMed

Rubach, M P; Pavlisko, E N; Perfect, J R

2013-08-01

We describe a case of pericarditis and large pericardial effusion in a 63-year-old African-American man undergoing autologous hematopoietic stem cell transplant for multiple myeloma. Pericardial tissue biopsy demonstrated fibrinous pericarditis, and immunohistochemistry stains were positive for respiratory syncytial virus. The patient improved with oral ribavirin and intravenous immune globulin infusions. © 2013 John Wiley & Sons A/S.

In immune defense: redefining the role of the immune system in chronic disease.

PubMed

Rubinow, Katya B; Rubinow, David R

2017-03-01

The recognition of altered immune system function in many chronic disease states has proven to be a pivotal advance in biomedical research over the past decade. For many metabolic and mood disorders, this altered immune activity has been characterized as inflammation, with the attendant assumption that the immune response is aberrant. However, accumulating evidence challenges this assumption and suggests that the immune system may be mounting adaptive responses to chronic stressors. Further, the inordinate complexity of immune function renders a simplistic, binary model incapable of capturing critical mechanistic insights. In this perspective article, we propose alternative paradigms for understanding the role of the immune system in chronic disease. By invoking allostasis or systems biology rather than inflammation, we can ascribe greater functional significance to immune mediators, gain newfound appreciation of the adaptive facets of altered immune activity, and better avoid the potentially disastrous effects of translating erroneous assumptions into novel therapeutic strategies.

Immune system and melanoma biology: a balance between immunosurveillance and immune escape.

PubMed

Passarelli, Anna; Mannavola, Francesco; Stucci, Luigia Stefania; Tucci, Marco; Silvestris, Francesco

2017-12-01

Melanoma is one of the most immunogenic tumors and its relationship with host immune system is currently under investigation. Many immunomodulatory mechanisms, favoring melanomagenesis and progression, have been described to interfere with the disablement of melanoma recognition and attack by immune cells resulting in immune resistance and immunosuppression. This knowledge produced therapeutic advantages, such as immunotherapy, aiming to overcome the immune evasion. Here, we review the current advances in cancer immunoediting and focus on melanoma immunology, which involves a dynamic interplay between melanoma and immune system, as well as on effects of "targeted therapies" on tumor microenvironment for combination strategies.

Tolerance induction of IgG+ memory B cells by T cell-independent type II antigens.

PubMed

Haniuda, Kei; Nojima, Takuya; Ohyama, Kyosuke; Kitamura, Daisuke

2011-05-15

Memory B cells generated during a T cell-dependent immune response rapidly respond to a secondary immunization by producing abundant IgG Abs that bind cognate Ag with high affinity. It is currently unclear whether this heightened recall response by memory B cells is due to augmented IgG-BCR signaling, which has only been demonstrated in the context of naive transgenic B cells. To address this question, we examined whether memory B cells can respond in vivo to Ags that stimulate only through BCR, namely T cell-independent type II (TI-II) Ags. In this study, we show that the TI-II Ag (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll cannot elicit the recall response in mice first immunized with the T cell-dependent Ag NP-chicken γ-globulin. Moreover, the NP-Ficoll challenge in vivo as well as in vitro significantly inhibits a subsequent recall response to NP-chicken γ-globulin in a B cell-intrinsic manner. This NP-Ficoll-mediated tolerance is caused by the preferential elimination of IgG(+) memory B cells binding to NP with high affinity. These data indicate that BCR cross-linking with a TI-II Ag does not activate IgG(+) memory B cells, but rather tolerizes them, identifying a terminal checkpoint of memory B cell differentiation that may prevent autoimmunity.

Passive immunization of mice pups through oral immunization of dams with a plant-derived vaccine.

PubMed

Walmsley, Amanda M; Kirk, Dwayne D; Mason, Hugh S

2003-03-03

Passive immunization plays an important role in protecting young mammals against pathogens before the maturation of their own immune systems. Although many reports have shown active immunization of animals and human through the use of plant-derived vaccines, only one report has given evidence of passive immunization of offspring through oral immunization of parents using plant-derived vaccines. In this case, a challenge alone provided the evidence of passive immunization and the mechanism through which this occurred was not investigated. This report describes the first step in elucidating the mechanism of passive immunization of offspring through actively immunizing the female parent through an orally delivered, plant-derived vaccine. The authors found passive immunization of offspring was caused by transfer of antigen-specific IgG through either transplacental transfer or ingesting colostrum. Future studies will investigate the roles of transplacental antibody transfer and ingesting colostrum in passive immunization and the possible involvement of IgA in this immunization route.

Immune System

EPA Science Inventory

A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

γδ T cell and other immune cells crosstalk in cellular immunity.

PubMed

He, Ying; Wu, Kangni; Hu, Yongxian; Sheng, Lixia; Tie, Ruxiu; Wang, Binsheng; Huang, He

2014-01-01

γδ T cells have been recognized as effectors with immunomodulatory functions in cellular immunity. These abilities enable them to interact with other immune cells, thus having the potential for treatment of various immune-mediated diseases with adoptive cell therapy. So far, the interactions between γδ T cell and other immune cells have not been well defined. Here we will discuss the interactivities among them and the perspective on γδ T cells for their use in immunotherapy could be imagined. The understanding of the crosstalk among the immune cells in immunopathology might be beneficial for the clinical application of γδ T cell.

Anti-thymocyte globulin induces neoangiogenesis and preserves cardiac function after experimental myocardial infarction.

PubMed

Lichtenauer, Michael; Mildner, Michael; Werba, Gregor; Beer, Lucian; Hoetzenecker, Konrad; Baumgartner, Andrea; Hasun, Matthias; Nickl, Stefanie; Mitterbauer, Andreas; Zimmermann, Matthias; Gyöngyösi, Mariann; Podesser, Bruno Karl; Klepetko, Walter; Ankersmit, Hendrik Jan

2012-01-01

Acute myocardial infarction (AMI) followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries. Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG) was evaluated in this study. AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat) was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01). Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG. These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI.

Cancer immunoediting by the innate immune system in the absence of adaptive immunity

PubMed Central

O’Sullivan, Timothy; Saddawi-Konefka, Robert; Vermi, William; Koebel, Catherine M.; Arthur, Cora; White, J. Michael; Uppaluri, Ravi; Andrews, Daniel M.; Ngiow, Shin Foong; Teng, Michele W.L.; Smyth, Mark J.; Schreiber, Robert D.

2012-01-01

Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3′methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2−/−, and RAG2−/−x γc−/− mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2−/−x γc−/− mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting. PMID:22927549

[Mucosal immunity with emphasis on urinary tract immunity and diabetes].

PubMed

Krejsek, J; Kudlová, M; Kolácková, M; Novosad, J

2008-05-01

Protective immune response in urinary tract is frequently impaired in patients with diabetes. Immunity in this mucosal compartment displays unique characteristics; e.g. absence of physiological microflora and lack of mucus. Pathogens are identified by the PRR receptors expressed on both epithelial and immune cells. Inflammatory response characterised by the acumulation ofgranulocytes is followed. Both protective and harm characteristics of inflammatory response are inseparable linked and delineated by gene polymorphisms in PRR receptors.

Validation of Procedures for Monitoring Crewmember Immune Function SDBI-1900, SMO-015 - Integrated Immune

NASA Technical Reports Server (NTRS)

Crucian, Brian; Stowe, Raymond; Mehta, Satish; Uchakin, Peter; Nehlsen-Cannarella, Sandra; Morukov, Boris; Pierson, Duane; Sams, Clarence

2007-01-01

There is ample evidence to suggest that space flight leads to immune system dysregulation. This may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk from prolonged immune dysregulation during space flight are not yet determined, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. Each of the clinical events resulting from immune dysfunction has the potential to impact mission critical objectives during exploration-class missions. To date, precious little in-flight immune data has been generated to assess this phenomenon. The majority of recent flight immune studies have been post-flight assessments, which may not accurately reflect the in-flight condition. There are no procedures currently in place to monitor immune function or its effect on crew health. The objective of this Supplemental Medical Objective (SMO) is to develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. This SMO will assess the clinical risks resulting from the adverse effects of space flight on the human immune system and will validate a flight-compatible immune monitoring strategy. Characterization of the clinical risk and the development of a monitoring strategy are necessary prerequisite activities prior to validating countermeasures. This study will determine, to the best level allowed by current technology, the in-flight status of crewmembers immune system. Pre-flight, in-flight and post-flight assessments of immune status, immune function, viral reactivation and physiological stress will be performed. The in-flight samples will allow a distinction between legitimate in-flight alterations and the physiological stresses of landing and readaptation which are believed to alter landing day assessments. The overall status of the immune system during flight (activation

Immunization Equity.

PubMed

Hinman, Alan R; McKinlay, Mark A

2015-12-01

Health inequities are the unjust differences in health among different social groups. Unfortunately, inequities are the norm, both in terms of health status and access to, and use of, health services. Childhood immunizations reduce the incidence of vaccine-preventable diseases and represent a cost-effective way to foster health equity. This paper reflects a 2015 review of data from surveys conducted in developing countries from 2005 to 2011 that show significant inequities in immunization coverage and discusses several initiatives currently underway (including Gavi, the Vaccine Alliance) that are directed at increasing childhood immunizations or reducing or abolishing overall health inequities. These initiatives have already had a significant impact on disease burden and childhood mortality and give rise to optimism that health disparities may further be reduced and health equity achieved as a result of investments made in immunization. Copyright © 2015 2015 by American Journal of Preventive Medicine and Els. Published by Elsevier Inc. All rights reserved.

Instant Childhood Immunization Schedule

MedlinePlus

... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

Unsolved Puzzles Surrounding HCV Immunity: Heterologous Immunity Adds Another Dimension.

PubMed

Agrawal, Babita; Singh, Shakti; Gupta, Nancy; Li, Wen; Vedi, Satish; Kumar, Rakesh

2017-07-27

Chronic infection with hepatitis C virus (HCV) afflicts 3% of the world's population and can lead to serious and late-stage liver diseases. Developing a vaccine for HCV is challenging because the correlates of protection are uncertain and traditional vaccine approaches do not work. Studies of natural immunity to HCV in humans have resulted in many enigmas. Human beings are not immunologically naïve because they are continually exposed to various environmental microbes and antigens, creating large populations of memory T cells. Heterologous immunity occurs when this pool of memory T cells cross-react against a new pathogen in an individual. Such heterologous immunity could influence the outcome when an individual is infected by a pathogen. We have recently made an unexpected finding that adenoviruses, a common environmental pathogen and an experimental vaccine vector, can induce robust cross-reactive immune responses against multiple antigens of HCV. Our unique finding of previously uncharacterized heterologous immunity against HCV opens new avenues to understand HCV pathogenesis and develop effective vaccines.

Origins of adaptive immunity.

PubMed

Liongue, Clifford; John, Liza B; Ward, Alister

2011-01-01

Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

Immunity, ageing and cancer

PubMed Central

Derhovanessian, Evelyna; Solana, Rafael; Larbi, Anis; Pawelec, Graham

2008-01-01

Compromised immunity contributes to the decreased ability of the elderly to control infectious disease and to their generally poor response to vaccination. It is controversial as to how far this phenomenon contributes to the well-known age-associated increase in the occurrence of many cancers in the elderly. However, should the immune system be important in controlling cancer, for which there is a great deal of evidence, it is logical to propose that dysfunctional immunity in the elderly would contribute to compromised immunosurveillance and increased cancer occurrence. The chronological age at which immunosenescence becomes clinically important is known to be influenced by many factors, including the pathogen load to which individuals are exposed throughout life. It is proposed here that the cancer antigen load may have a similar effect on "immune exhaustion" and that pathogen load and tumor load may act additively to accelerate immunosenescence. Understanding how and why immune responsiveness changes in humans as they age is essential for developing strategies to prevent or restore dysregulated immunity and assure healthy longevity, clearly possible only if cancer is avoided. Here, we provide an overview of the impact of age on human immune competence, emphasizing T-cell-dependent adaptive immunity, which is the most sensitive to ageing. This knowledge will pave the way for rational interventions to maintain or restore appropriate immune function not only in the elderly but also in the cancer patient. PMID:18816370

Immunization of complex networks

NASA Astrophysics Data System (ADS)

Pastor-Satorras, Romualdo; Vespignani, Alessandro

2002-03-01

Complex networks such as the sexual partnership web or the Internet often show a high degree of redundancy and heterogeneity in their connectivity properties. This peculiar connectivity provides an ideal environment for the spreading of infective agents. Here we show that the random uniform immunization of individuals does not lead to the eradication of infections in all complex networks. Namely, networks with scale-free properties do not acquire global immunity from major epidemic outbreaks even in the presence of unrealistically high densities of randomly immunized individuals. The absence of any critical immunization threshold is due to the unbounded connectivity fluctuations of scale-free networks. Successful immunization strategies can be developed only by taking into account the inhomogeneous connectivity properties of scale-free networks. In particular, targeted immunization schemes, based on the nodes' connectivity hierarchy, sharply lower the network's vulnerability to epidemic attacks.

[Relationship between BCG immunization coverage and the immunization delivery system in the Tama area of Tokyo].

PubMed

Sugishita, Yoshiyuki; Hayashi, Kunihiko; Mori, Toru; Horiguchi, Itsuko; Marui, Eiji

2012-03-01

The BCG immunization has long been performed in Japan. Although the BCG immunization service is the responsibility of the municipality, the manner in which the BCG immunization is delivered differs from municipality to municipality. The purpose of this study was to clarify how the different manner of the BCG immunization delivery systems influenced the BCG immunization coverage. The study of BCG immunization coverage was conducted in the Tama area located in the western suburbs of Tokyo in 2004. The birth data and the immunization history by the age of 3 years were collected in the three-year-old health check-up from a total of 2,341 children residing in the Tama area. Based on the age at immunization for each child, the BCG immunization coverage was calculated according to the types of the BCG immunization delivery system. The immunization types were defined as follows; the BCG immunization given on the occasion of the mass health check-up (Group 1); the exclusive mass BCG immunization in a monthly service (Group 2); the exclusive mass BCG immunization in a bimonthly service (Group 3); the exclusive mass BCG immunization in services of fewer than every two months (Group 4); and the immunization given on an individual basis by a general practitioner (Group 5). A univariate analysis was performed to examine the relationship between the BCG immunization coverage by the age of 6 months and the difference among the BCG immunization delivery systems, followed by a multivariate regression analysis to adjust for the factors related to the demography, health care services and the socio-economic status of the municipalities. Unadjusted odds ratios and adjusted odds ratios for BCG unimmunized children under the age of 6 months by the BCG immunization delivery manner groups were OR 1 reference, adj. OR 1 reference in Group 1; OR 1.42 CI 0.87-2.29, adj. OR 4.01 CI 2.24-7.11 in Group 2; OR 4.96 CI 3.66-6.82, adj. OR 15.59 CI 10.10-24.49 in Group 3;OR 18.60 CI 13.77-25.49, adj

Immune system

USDA-ARS?s Scientific Manuscript database

This chapter is an update on the swine Immune System. It will be Chapter 16 in the 11th Edition (2018) of Diseases of Swine. The chapter outlines all aspects of the swine immune system in development and in responses to infection and vaccination. It illustrates the tremendous influence that the immu...

Immune Disorder HSCT Protocol

ClinicalTrials.gov

2017-11-17

Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

STUDIES ON THE ANTIGENIC PROPERTIES OF COMPLEMENT

PubMed Central

Klein, Paul G.; Burkholder, Peter M.

1960-01-01

Evidence is presented to show that guinea pig complement fixed on sensitized sheep red cells acts as a specific agglutinogen. Agglutinating antibodies that react with cell-fixed complement can be produced by immunizing rabbits with a complex of stromata-amboceptor-complement or with guinea pig serum globulin. These agglutinins can be removed by precipitation with guinea pig serum. They are, therefore, distinct from immunoconglutinins. PMID:14409702

Cellular Sites of Immunologic Unresponsiveness*

PubMed Central

Chiller, Jacques M.; Habicht, Gail S.; Weigle, William O.

1970-01-01

The reconstitution of the immune response of lethally irradiated mice to human γ-globulin is dependent on the synergistic action of bone marrow with thymus cells. Immunologic unresponsiveness appears to involve a functional defect at each of these cellular levels, inasmuch as neither bone marrow nor thymus cells from unresponsive donors are capable of demonstrating synergism in combination with their normal counterpart. PMID:4192271

Innate immune memory in plants.

PubMed

Reimer-Michalski, Eva-Maria; Conrath, Uwe

2016-08-01

The plant innate immune system comprises local and systemic immune responses. Systemic plant immunity develops after foliar infection by microbial pathogens, upon root colonization by certain microbes, or in response to physical injury. The systemic plant immune response to localized foliar infection is associated with elevated levels of pattern-recognition receptors, accumulation of dormant signaling enzymes, and alterations in chromatin state. Together, these systemic responses provide a memory to the initial infection by priming the remote leaves for enhanced defense and immunity to reinfection. The plant innate immune system thus builds immunological memory by utilizing mechanisms and components that are similar to those employed in the trained innate immune response of jawed vertebrates. Therefore, there seems to be conservation, or convergence, in the evolution of innate immune memory in plants and vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immune drug discovery from venoms.

PubMed

Jimenez, Rocio; Ikonomopoulou, Maria P; Lopez, J Alejandro; Miles, John J

2018-01-01

This review catalogues recent advances in knowledge on venoms as standalone therapeutic agents or as blueprints for drug design, with an emphasis on venom-derived compounds that affects the immune system. We discuss venoms and venom-derived compounds that affect total immune cell numbers, immune cell proliferation, immune cell migration, immune cell phenotype and cytokine secretion. Identifying novel compounds that 'tune' the system, up-regulating the immune response during infectious disease and cancer and down-regulating the immune response during autoimmunity, will greatly expand the tool kit of human immunotherapeutics. Targeting these pathways may also open therapeutic options that alleviate symptoms of envenomation. Finally, combining recent advances in venomics with progress in low cost, high-throughput screening platforms will no doubt yield hundreds of prototype immune modulating compounds in the coming years. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immune Antibody Libraries: Manipulating The Diverse Immune Repertoire for Antibody Discovery.

PubMed

Lim, Theam Soon; Chan, Soo Khim

2016-01-01

Antibody phage display is highly dependent on the availability of antibody libraries. There are several forms of libraries depending mainly on the origin of the source materials. There are three major classes of libraries, mainly the naïve, immune and synthetic libraries. Immune antibody libraries are designed to isolate specific and high affinity antibodies against disease antigens. The pre-exposure of the host to an infection results in the production of a skewed population of antibodies against the particular infection. This characteristic takes advantage of the in vivo editing machinery to generate bias and specific immune repertoire. The skewed but diverse repertoire of immune libraries has been adapted successfully in the generation of antibodies against a wide range of diseases. We envisage immune antibody libraries to play a greater role in the discovery of antibodies for diseases in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Immune-based therapies.

PubMed

Lein, B

1995-12-01

Several immune-based HIV therapy studies presented at the Interscience Conference on Antimicrobial Agents Chemotherapy (ICAAC) are summarized. These studies involve the following therapies: HIV-IT, a gene therapy approach to augmenting the body's anti-HIV responses; interferon-alpha n3, a new formulation of alpha interferon with fewer toxicities; transfer of immune responses from one individual to another, also called passive immune therapy; and interleukin-2 (IL-2) in combination with protease inhibitors.

Sex hormone-binding globulin b expression in the rainbow trout ovary prior to sex differentiation.

PubMed

Pérez, Claudio; Araneda, Cristian; Estay, Francisco; Díaz, Nelson F; Vizziano-Cantonnet, Denise

2018-04-01

Salmonids have two sex hormone-binding globulin (Shbg) paralogs. Shbga is mainly expressed in the liver, while Shbgb is secreted by the granulosa cells of the rainbow trout ovary. Coexpression of shbgb and the gonadal aromatase cyp19a1a mRNAs been observed in granulosa cells, suggesting a physiological coordination between Shbgb expression and estrogen synthesis. As estrogens are essential for female sex determination in the fish ovary, we propose that Shbgb participates in early ovarian differentiation, either by binding with estrogen or through another mechanism that remains to be discovered. To elucidate this potential role, monosex populations of female trout were studied during the molecular ovarian differentiation period (28-56 dpf). shbgb mRNA expression was measured using qPCR and compared with expression of genes for other ovarian markers (cyp19a1a, foxl2, follistatin, and estrogen receptors). shbgb transcript expression was detected during the final stages of embryonic development (21-26 dpf) and during molecular ovarian differentiation (32-52 dpf) after hatching (which occurred at 31 dpf). In situ hybridization localized shbgb transcription to the undifferentiated ovary at 42 dpf, and shbgb and cyp19a1a mRNA showed similar expression patterns. These results suggest that Shbgb is involved in early ovarian differentiation, supporting an important role for the salmonid shbgb gene in sex determination. Copyright © 2017 Elsevier Inc. All rights reserved.

Your Child's Immunization Record

MedlinePlus

Your Child’s Immunization Record It’s important to keep up-to-date records of all your child’s immunizations, beginning at birth and continuing through ... receives a vaccination by filling in the date. Record of Immunizations Date Given: Where Given: Reaction: Hepatitis ...

Effects of dietary onion (Allium cepa) powder on growth, innate immune response and hemato-biochemical parameters of beluga (Huso huso Linnaeus, 1754) juvenile.

PubMed

Akrami, Raza; Gharaei, Ahmad; Mansour, Majid Razeghi; Galeshi, Ali

2015-08-01

The present study was aimed at determining the effects of dietary onion powder on growth, innate immune response and hemato-biochemical parameters of beluga juvenile (Huso huso). Basal diets containing onion powder 0 (control), 0.5 and 1% of feed were fed to beluga juvenile. At the end of the experiment, the highest weight gain (WG%) and specific growth rate (SGR) was observed in group fed with 1% onion (P < 0.05). There were no significant difference (P > 0.05) about feed conversion ratio (FCR) in treatment groups that fed diets containing various levels of onion powder. After 8 weeks, serum lysozyme activity, superoxide dismutase activity (SOD), respiratory burst activity and serum total immunoglobulin (Ig) showed a significant increase in treatment group with 1% onion powder compared to other groups (P < 0.05). The group fed 1% onion showed a significantly increases in the number of erythrocytes (RBC), leucocyte (WBC), haematocrit (Hct) levels compared to the control group (P < 0.05). Haemoglobin, monocyte, lymphocyte and neutrophil had no significant change (P > 0.05) in treatment groups and control. The analysis of AST and LDH levels showed a significant decrease in 1% onion compared to the control and 0.5% onion diet (P < 0.05), while ALT and ALP levels were not influenced (P > 0.05). The blood glucose, total protein, triglyceride, cholesterol, albumin and globulin levels were lower in treated groups compared with the control (P < 0.05). The results of this study demonstrated that dietary onion powder could be an improvement in growth, hematological parameters and immune function of beluga juvenile. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hapten-specific T-Cell Unresponsiveness Induced by Benzylpenicilloyl Autologous Gamma Globulin Conjugates in Human Lymphocytes In Vitro

PubMed Central

Geha, Raif S.; Fruchter, Lazar; Borel, Yves

1980-01-01

The aim of these studies was to determine whether unresponsiveness to the main determinant of penicillin, benzylpenicilloyl, can be induced in human peripheral lymphocytes in vitro by conjugates of benzylpenicilloyl (BPO) autologous gamma globulin (HGG). Initially it was shown that conjugates of BPO-keyhole limpet hemocyanin (KLH) elicited lymphocyte proliferation in the peripheral blood lymphocytes of six out of nine adult individuals in vitro. In contrast, conjugates of dinitrophenylated KLH and of BPO-HGG and the carriers HGG and KLH alone failed to do so. Similarly, release of the non-specific helper factor, lymphocyte mitogenic factor (LMF) occurred only after BPO-KLH stimulation. LMF activity was measured by B-cell proliferation and incorporation of radioactive amino acids into secreted immunoglobulin. Treatment with BPO-HGG for 24 h in vitro inhibited BPO-KLH-induced lymphocyte proliferation and LMF release. Treatment with either HGG, dinitrophenylated HGG, BPO-KLH, or BPO-human serum albumin failed to abrogate T-cell lymphocyte proliferation of human lymphocytes in vitro. The antigen specificity of the reduced immunologic responsiveness was further demonstrated by the observation that lymphocytes treated with BPO-HGG for 24 h in vitro responded normally to tetanus toxoid antigen. The data suggest that conjugates of BPO-HGG induce hapten-specific helper T-cell unresponsiveness in vitro. PMID:6157701

Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning.

PubMed

Rezvani, A R; Kanate, A S; Efron, B; Chhabra, S; Kohrt, H E; Shizuru, J A; Laport, G G; Miklos, D B; Benjamin, J E; Johnston, L J; Arai, S; Weng, W-K; Negrin, R S; Strober, S; Lowsky, R

2015-10-01

We describe 47 patients with lymphoma and failed prior autologous hematopoietic cell transplantation (HCT) who received TLI-ATG (anti-thymocyte globulin) conditioning followed by allogeneic HCT. Thirty-two patients had non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma (n=19), T-cell NHL (n=6), mantle cell lymphoma (n=4) or other B-cell subtypes (n=3)), and 15 had Hodgkin lymphoma. The median follow-up was 4.9 (range, 2.1-11.9) years. The cumulative incidence of grade II-IV acute GvHD at day +100 was 12%, and the cumulative incidence of extensive chronic GvHD at 1 year was 36%. The 3-year cumulative incidences of overall survival (OS), PFS and non-relapse mortality (NRM) were 81%, 44% and 7%, respectively. Fifteen patients died (relapse, n=10; NRM, n=5). Among the 25 patients with relapse after allogeneic HCT, 11 (44%) achieved durable (>1 year) CRs following donor lymphocyte infusion or chemoradiotherapy. The majority of surviving patients (75%; n=24) were able to discontinue all immunosuppression. For patients with relapsed lymphoma after autologous HCT, allogeneic HCT using TLI-ATG conditioning is a well-tolerated, predominantly outpatient therapy with low NRM (7% at 3 years), a low incidence of GvHD, durable disease control and excellent OS (81% at 3 years).

Immunometabolic circuits in trained immunity.

PubMed

Arts, Rob J W; Joosten, Leo A B; Netea, Mihai G

2016-10-01

The classical view that only adaptive immunity can build immunological memory has recently been challenged. Both in organisms lacking adaptive immunity as well as in mammals, the innate immune system can adapt to mount an increased resistance to reinfection, a de facto innate immune memory termed trained immunity. Recent studies have revealed that rewiring of cellular metabolism induced by different immunological signals is a crucial step for determining the epigenetic changes underlying trained immunity. Processes such as a shift of glucose metabolism from oxidative phosphorylation to aerobic glycolysis, increased glutamine metabolism and cholesterol synthesis, play a crucial role in these processes. The discovery of trained immunity opens the door for the design of novel generations of vaccines, for new therapeutic strategies for the treatment of immune deficiency states, and for modulation of exaggerated inflammation in autoinflammatory diseases. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immune Dysfunction in Cirrhosis

PubMed Central

Noor, Mohd Talha; Manoria, Piyush

2017-01-01

Abstract Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body. Cirrhosis-associated immune dysfunction leads to alterations in both innate and acquired immunity, due to defects in the local immunity of liver as well as in systemic immunity. Cirrhosis-associated immune dysfunction is a dynamic phenomenon, comprised of both increased systemic inflammation and immunodeficiency, and is responsible for 30% mortality. It also plays an important role in acute as well as chronic decompensation. Immune paralysis can accompany it, which is characterized by increase in anti-inflammatory cytokines and suppression of proinflammatory cytokines. There is also presence of increased gut permeability, reduced gut motility and altered gut flora, all of which leads to increased bacterial translocation. This increased bacterial translocation and consequent endotoxemia leads to increased blood stream bacterial infections that cause systemic inflammatory response syndrome, sepsis, multiorgan failure and death. The gut microbiota of cirrhotic patients has more pathogenic microbes than that of non-cirrhotic individuals, and this disturbs the homeostasis and favors gut translocation. Prompt diagnosis and treatment of such infections are necessary for better survival. We have reviewed the various mechanisms of immune dysfunction and its consequences in cirrhosis. Recognizing the exact pathophysiology of immune dysfunction will help treating clinicians in avoiding its complications in their patients and can lead to newer therapeutic interventions and reducing the morbidity and mortality rates. PMID:28507927

Immunity in the spleen and blood of mice immunized with irradiated Toxoplasma gondii tachyzoites.

PubMed

Zorgi, Nahiara Esteves; Galisteo, Andrés Jimenez; Sato, Maria Notomi; do Nascimento, Nanci; de Andrade, Heitor Franco

2016-08-01

Toxoplasma gondii infection induces a strong and long-lasting immune response that is able to prevent most reinfections but allows tissue cysts. Irradiated, sterilized T. gondii tachyzoites are an interesting vaccine, and they induce immunity that is similar to infection, but without cysts. In this study, we evaluated the cellular immune response in the blood and spleen of mice immunized with this preparation by mouth (v.o.) or intraperitoneally (i.p.) and analyzed the protection after challenge with viable parasites. BALB/c mice were immunized with three i.p. or v.o. doses of irradiated T. gondii tachyzoites. Oral challenge with ten cysts of the ME-49 or VEG strain at 90 days after the last dose resulted in high levels of protection with low parasite burden in the immunized animals. There were higher levels of specific IgG, IgA and IgM antibodies in the serum, and the i.p. immunized mice had higher levels of the high-affinity IgG and IgM antibodies than the orally immunized mice, which had more high-affinity IgA antibodies. B cells (CD19(+)), plasma cells (CD138(+)) and the CD4(+) and CD8(+) T cell populations were increased in both the blood and spleen. Cells from the spleen of the i.p. immunized mice also showed antigen-induced production of interleukin-10 (IL-10), interferon gamma (IFN-γ) and interleukin 4 (IL-4). The CD4(+) T cells, B cells and likely CD8(+) T cells from the spleens of the i.p. immunized mice proliferated with a specific antigen. The protection was correlated with the spleen and blood CD8(+) T cell, high-affinity IgG and IgM and antigen-induced IL-10 and IL-4 production. Immunization with irradiated T. gondii tachyzoites induces an immune response that is mediated by B cells and CD4(+) and CD8(+) T cells, with increased humoral and cellular immune responses that are necessary for host protection after infection. The vaccine is similar to natural infection, but free of tissue cysts; this immunity restrains infection at challenge and can be an

Estimation of immunization providers' activities cost, medication cost, and immunization dose errors cost in Iraq.

PubMed

Al-lela, Omer Qutaiba B; Bahari, Mohd Baidi; Al-abbassi, Mustafa G; Salih, Muhannad R M; Basher, Amena Y

2012-06-06

The immunization status of children is improved by interventions that increase community demand for compulsory and non-compulsory vaccines, one of the most important interventions related to immunization providers. The aim of this study is to evaluate the activities of immunization providers in terms of activities time and cost, to calculate the immunization doses cost, and to determine the immunization dose errors cost. Time-motion and cost analysis study design was used. Five public health clinics in Mosul-Iraq participated in the study. Fifty (50) vaccine doses were required to estimate activities time and cost. Micro-costing method was used; time and cost data were collected for each immunization-related activity performed by the clinic staff. A stopwatch was used to measure the duration of activity interactions between the parents and clinic staff. The immunization service cost was calculated by multiplying the average salary/min by activity time per minute. 528 immunization cards of Iraqi children were scanned to determine the number and the cost of immunization doses errors (extraimmunization doses and invalid doses). The average time for child registration was 6.7 min per each immunization dose, and the physician spent more than 10 min per dose. Nurses needed more than 5 min to complete child vaccination. The total cost of immunization activities was 1.67 US$ per each immunization dose. Measles vaccine (fifth dose) has a lower price (0.42 US$) than all other immunization doses. The cost of a total of 288 invalid doses was 744.55 US$ and the cost of a total of 195 extra immunization doses was 503.85 US$. The time spent on physicians' activities was longer than that spent on registrars' and nurses' activities. Physician total cost was higher than registrar cost and nurse cost. The total immunization cost will increase by about 13.3% owing to dose errors. Copyright © 2012 Elsevier Ltd. All rights reserved.

General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP).

PubMed

2011-01-28

This report is a revision of the General Recommendations on Immunization and updates the 2006 statement by the Advisory Committee on Immunization Practices (ACIP) (CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2006;55[No. RR-15]). The report also includes revised content from previous ACIP recommendations on the following topics: adult vaccination (CDC. Update on adult immunization recommendations of the immunization practices Advisory Committee [ACIP]. MMWR 1991;40[No. RR-12]); the assessment and feedback strategy to increase vaccination rates (CDC. Recommendations of the Advisory Committee on Immunization Practices: programmatic strategies to increase vaccination rates-assessment and feedback of provider-based vaccination coverage information. MMWR 1996;45:219-20); linkage of vaccination services and those of the Supplemental Nutrition Program for Women, Infants, and Children (WIC program) (CDC. Recommendations of the Advisory Committee on Immunization Practices: programmatic strategies to increase vaccination coverage by age 2 years-linkage of vaccination and WIC services. MMWR 1996;45:217-8); adolescent immunization (CDC. Immunization of adolescents: recommendations of the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American Medical Association. MMWR 1996;45[No. RR-13]); and combination vaccines (CDC. Combination vaccines for childhood immunization: recommendations of the Advisory Committee on Immunization Practices [ACIP], the American Academy of Pediatrics [AAP], and the American Academy of Family Physicians [AAFP]. MMWR 1999;48[No. RR-5]). Notable revisions to the 2006 recommendations include 1) revisions to the tables of contraindications and precautions to vaccination, as well as a separate table of conditions that are commonly misperceived as contraindications and precautions; 2

Immunizations for foreign travel.

PubMed Central

Hill, D. R.

1992-01-01

One of the most important aspects of preparing travelers for destinations throughout the world is providing them with immunizations. Before administering any vaccines, however, a careful health and immunization history and travel itinerary should be obtained in order to determine vaccine indications and contraindications. There are three categories of immunizations for foreign travel. The first category includes immunizations which are routinely recommended whether or not the individual is traveling. Many travelers are due for primary vaccination or boosting against tetanus-diphtheria, measles-mumps-rubella, pneumococcal pneumonia, and influenza, for example, and the pre-travel visit is an ideal time to administer these. The second category are immunizations which might be required by a country as a condition for entry; these are yellow fever and cholera. The final category contains immunizations which are recommended because there is a risk of acquiring a particular disease during travel. Typhoid fever, meningococcal disease, rabies, and hepatitis are some examples. Travelers who are pregnant or who are infected with the human immunodeficiency virus require special consideration. Provision of appropriate immunizations for foreign travel is an important aspect of preventing illness in travelers. PMID:1337807

Rebuilding immunity with Remune.

PubMed

Whitfield, L

1998-01-01

Remune, an immune response therapy composed of inactivated HIV, is designed to enhance the immune system's ability to recognize and kill HIV proteins. Developed by Dr. Jonas Salk, researchers hope Remune's actions can alter the course of HIV infection and slow disease progression. Remune has gained Food and Drug Administration (FDA) approval to enter the critical Phase III trial stage. Two clinical trials are tracking Remune's immunogenicity (ability to provoke an immune response), its immunogenicity relative to dose level, and its effect on viral load. An ongoing trial, approved in February of 1996, enrolled 2,500 patients at 74 sites. The manufacturer, Immune Response Corporation (IRC), announced earlier this year that treatment with Remune induces an immune response to HIV that cross-reacts with different strains of the virus. This immune response is crucial for developing an effective worldwide treatment. Remune decreases levels of tumor necrosis factor alpha (TNF-a). IRC recently began a Phase I clinical trial in Great Britain that combines Remune with a protease inhibitor, two antiviral nucleoside analogues, and Interleukin-2. The trial is designed to determine the role that the drug may play in restoring immune response.

Nationwide survey on the use of horse antithymocyte globulins (ATGAM) in patients with acquired aplastic anemia: A report on behalf of the French Reference Center for Aplastic Anemia.

PubMed

Peffault de Latour, Régis; Tabrizi, Reza; Marcais, Ambroise; Leblanc, Thierry; Lamy, Thierry; Mohty, Mohamad; Tavitian, Suzanne; Jubert, Charlotte; Pasquet, Marlène; Galambrun, Claire; Nguyen, Stéphanie; Cahn, Jean Yves; Braun, Thorsten; Deconinck, Eric; Bay, Jacques Olivier; Sicre de Fontbrune, Flore; Barraco, Fiorenza; Socié, Gérard

2018-05-01

Antithymocyte globulins (ATG) plus cyclosporine (CSA) is the gold standard immunosuppressive treatment (IST) for patients with aplastic anemia. A prospective randomized trial showed in 2011 that hATG was superior to rabbit ATG for first-line treatment of severe AA. The French Health Agency (ANSM) permitted a patient-named authorization for temporary use (ATU) program of hATG (ATGAM, Pfizer) in patients with AA in 2011 since commercial access to hATG is not approved. We took advantage of this program to analyze the outcomes of 465 patients who received antithymocyte globulins (ATGAM) plus CSA as first line treatment (n = 379; 81.5%), or for refractory (n = 26) or relapsed disease (n = 33), from September 2011 to March 2017. In the entire cohort one year, 72% of the patients had partial and 13% had complete response, with worse response for patients with severe AA and a longer interval between diagnosis and IST (more than 6 months). Severe adverse events were mainly linked to infections (24%), hemorrhages (6%), and elevated liver function tests (5%). Overall at 12 months, 9.7% of patients required second line IST and 15.6% received transplantation. Fifty-five patients died during the study mainly because of infections (53%). Factors predicting independently worse survival were age over 40 years, neutrophils less than 0.5 × 10 9 /L, male gender and longer delay between diagnosis and hATG (>6 months period). This study does illustrate the results of ATGAM with CSA in a true-life perspective and confirms ATGAM as standard of care IST to treat patients with AA not eligible for HSCT. © 2018 Wiley Periodicals, Inc.

HIV-associated chronic immune activation

PubMed Central

Paiardini, Mirko; Müller-Trutwin, Michaela

2013-01-01

Summary Systemic chronic immune activation is considered today as the driving force of CD4+ T-cell depletion and acquired immunodeficiency syndrome (AIDS). A residual chronic immune activation persists even in HIV-infected patients in which viral replication is successfully inhibited by antiretroviral therapy, with the extent of this residual immune activation being associated with CD4+ T-cell loss. Unfortunately, the causal link between chronic immune activation and CD4+ T-cell loss has not been formally established. This article provides first a brief historical overview on how the perception of the causative role of immune activation has changed over the years and lists the different kinds of immune activation that have been observed to be characteristic for human immunodeficiency virus (HIV) infection. The mechanisms proposed to explain the chronic immune activation are multiple and are enumerated here, as well as the mechanisms proposed on how chronic immune activation could lead to AIDS. In addition, we summarize the lessons learned from natural hosts that know how to ‘show AIDS the door’, and discuss how these studies informed the design of novel immune modulatory interventions that are currently being tested. Finally, we review the current approaches aimed at targeting chronic immune activation and evoke future perspectives. PMID:23772616

Pretransplant thymic function predicts acute rejection in antithymocyte globulin-treated renal transplant recipients.

PubMed

Bamoulid, Jamal; Courivaud, Cécile; Crepin, Thomas; Carron, Clémence; Gaiffe, Emilie; Roubiou, Caroline; Laheurte, Caroline; Moulin, Bruno; Frimat, Luc; Rieu, Philippe; Mousson, Christiane; Durrbach, Antoine; Heng, Anne-Elisabeth; Rebibou, Jean-Michel; Saas, Philippe; Ducloux, Didier

2016-05-01

Lack of clear identification of patients at high risk of acute rejection hampers the ability to individualize immunosuppressive therapy. Here we studied whether thymic function may predict acute rejection in antithymocyte globulin (ATG)-treated renal transplant recipients in 482 patients prospectively studied during the first year post-transplant of which 86 patients experienced acute rejection. Only CD45RA(+)CD31(+)CD4(+) T cell (recent thymic emigrant [RTE]) frequency (RTE%) was marginally associated with acute rejection in the whole population. This T-cell subset accounts for 26% of CD4(+) T cells. Pretransplant RTE% was significantly associated with acute rejection in ATG-treated patients (hazard ratio, 1.04; 95% confidence interval, 1.01-1.08) for each increased percent in RTE/CD4(+) T cells), but not in anti-CD25 monoclonal (αCD25 mAb)-treated patients. Acute rejection was significantly more frequent in ATG-treated patients with high pretransplant RTE% (31.2% vs. 16.4%) or absolute number of RTE/mm(3) (31.7 vs. 16.1). This difference was not found in αCD25 monclonal antibody-treated patients. Highest values of both RTE% (>31%, hazard ratio, 2.50; 95% confidence interval, 1.09-5.74) and RTE/mm(3) (>200/mm(3), hazard ratio, 3.71; 95% confidence interval, 1.59-8.70) were predictive of acute rejection in ATG-treated patients but not in patients having received αCD25 monoclonal antibody). Results were confirmed in a retrospective cohort using T-cell receptor excision circle levels as a marker of thymic function. Thus, pretransplant thymic function predicts acute rejection in ATG-treated patients. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

A successful desensitization protocol for horse-derived antithymocyte globulin in severe aplastic anemia.

PubMed

Demir, Esen; Cigerci Günaydın, Nurşen; Karadaş, Nihal; Gülen, Figen; Tanac, Remziye; Yılmaz, Deniz

2015-03-01

Horse antithymocyte globulin (h-ATG) (ATGAM(®) ) is the first choice of treatment in very severe patients with aplastic anemia who do not have any HLA matched sibling donor. h-ATG is a heterologous serum that may cause anaphylaxis. Alternative treatment strategies must be planned in case of hypersensitivity. Desensitization must be considered in patients without an alternative treatment of choice. We aimed to present the h-ATG desensitization protocol and consider its effectiveness in patients with aplastic anemia who are hypersensitized with h-ATG and do not have an alternative treatment of choice. Skin prick tests were performed with non-diluted solution in eight very severe patients with aplastic anemia who are followed up in Ege University Children's Hospital. Although skin prick test was found negative in these eight patients, different dilution h-ATG intradermal tests were performed and found positive in all patients. h-ATG desensitization program was started to these hypersensitized patients. Desensitization program was started to six male and two female very severe patients with aplastic anemia whose ages were between seven and 19 yr (median: 12.9 yr). All of the patients completed the desensitization program. While local reaction was seen in two patients, systemic reaction was seen in one patient and late reaction was seen in one patient during and after desensitization program. A successful desensitization program with h-ATG in children with aplastic anemia is presented. Even though there is not an exposure before to such high allergy potential heterologous serum, skin tests should be performed and desensitization must be started to patients who are hypersensitized to h-ATG. As the expected effectiveness of the treatment is so much, the desensitization protocol can be carried out safely and effectively with trained stuff although allergic reactions can be seen. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Tumor Profile in Primary Immune Deficiencies Challenges the Cancer Immune Surveillance Concept.

PubMed

Satgé, Daniel

2018-01-01

Under the concept of cancer immune surveillance, individuals with primary immune deficiencies would be expected to develop many more malignancies and show an excess of all types of cancers, compared to people with a normal immune system. A review of the nine most frequent and best-documented human conditions with primary immune deficiency reveals a 1.6- to 2.3-fold global increase of cancer in the largest epidemiological studies. However, the spectrum of cancer types with higher frequencies is narrow, limited mainly to lymphoma, digestive tract cancers, and virus-induced cancers. Increased lymphoma is also reported in animal models of immune deficiency. Overstimulation of leukocytes, chronic inflammation, and viruses explain this tumor profile. This raises the question of cancers being foreign organisms or tissues. Organisms, such as bacteria, viruses, and parasites as well as non-compatible grafts are seen as foreign (non-self) and identified and destroyed or rejected by the body (self). As cancer cells rarely show strong (and unique) surface antibodies, their recognition and elimination by the immune system is theoretically questionable, challenging the immune surveillance concept. In the neonatal period, the immune system is weak, but spontaneous regression and good outcomes occur for some cancers, suggesting that non-immune factors are effective in controlling cancer. The idea of cancer as a group of cells that must be destroyed and eliminated appears instead as a legacy of methods and paradigms in microbiological medicine. As an alternative approach, cancer cells could be considered part of the body and could be controlled by an embryonic and neonatal environment.

Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease.

PubMed

Vallejo, Abbe N

2007-03-01

Immunological studies of aging and of patients with chronic immune-mediated diseases document overlap of immune phenotypes. Here, the term "immune remodeling" refers to these phenotypes that are indicative of biological processes of deterioration and repair. This concept is explored through lessons from studies about the changes in the T-cell repertoire and the functional diversity of otherwise oligoclonal, senescent T cells. Immune remodeling suggests a gradual process that occurs throughout life. However, similar but more drastic remodeling occurs disproportionately among young patients with chronic disease. In this article, I propose that immune remodeling is a beneficial adaptation of aging to promote healthy survival beyond reproductive performance, but acute remodeling poses risk of premature exhaustion of the immune repertoire and, thus, is detrimental in young individuals.

The effect of maternal and paternal immune challenge on offspring immunity and reproduction in a cricket.

PubMed

McNamara, K B; van Lieshout, E; Simmons, L W

2014-06-01

Trans-generational immune priming is the transmission of enhanced immunity to offspring following a parental immune challenge. Although within-generation increased investment into immunity demonstrates clear costs on reproductive investment in a number of taxa, the potential for immune priming to impact on offspring reproductive investment has not been thoroughly investigated. We explored the reproductive costs of immune priming in a field cricket, Teleogryllus oceanicus. To assess the relative importance of maternal and paternal immune status, mothers and fathers were immune-challenged with live bacteria or a control solution and assigned to one of four treatments in which one parent, neither or both parents were immune-challenged. Families of offspring were reared to adulthood under a food-restricted diet, and approximately 10 offspring in each family were assayed for two measures of immunocompetence. We additionally quantified offspring reproductive investment using sperm viability for males and ovary mass for females. We demonstrate that parental immune challenge has significant consequences for the immunocompetence and, in turn, reproductive investment of their male offspring. A complex interaction between maternal and paternal immune status increased the antibacterial immune response of male offspring. This increased immune response was associated with a reduction in son's sperm viability, implicating a trans-generational resource trade-off between investment into immunocompetence and reproduction. Our data also show that these costs are sexually dimorphic, as daughters did not demonstrate a similar increase in immunity, despite showing a reduction in ovary mass. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

The cell-mediated immunity of Drosophila melanogaster: hemocyte lineages, immune compartments, microanatomy and regulation.

PubMed

Honti, Viktor; Csordás, Gábor; Kurucz, Éva; Márkus, Róbert; Andó, István

2014-01-01

In the animal kingdom, innate immunity is the first line of defense against invading pathogens. The dangers of microbial and parasitic attacks are countered by similar mechanisms, involving the prototypes of the cell-mediated immune responses, the phagocytosis and encapsulation. Work on Drosophila has played an important role in promoting an understanding of the basic mechanisms of phylogenetically conserved modules of innate immunity. The aim of this review is to survey the developments in the identification and functional definition of immune cell types and the immunological compartments of Drosophila melanogaster. We focus on the molecular and developmental aspects of the blood cell types and compartments, as well as the dynamics of blood cell development and the immune response. Further advances in the characterization of the innate immune mechanisms in Drosophila will provide basic clues to the understanding of the importance of the evolutionary conserved mechanisms of innate immune defenses in the animal kingdom. Copyright © 2013 Elsevier Ltd. All rights reserved.

Exercise and immunity

MedlinePlus

... medlineplus.gov/ency/article/007165.htm Exercise and immunity To use the sharing features on this page, ... know exactly if or how exercise increases your immunity to certain illnesses. There are several theories. However, ...

Immune System and Kidney Transplantation.

PubMed

Shrestha, Badri Man

2017-01-01

The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

The immune system as a biomonitor: explorations in innate and adaptive immunity

PubMed Central

Thomas, Niclas; Heather, James; Pollara, Gabriel; Simpson, Nandi; Matjeka, Theres; Shawe-Taylor, John; Noursadeghi, Mahdad; Chain, Benjamin

2013-01-01

The human immune system has a highly complex, multi-layered structure which has evolved to detect and respond to changes in the internal microenvironment of the body. Recognition occurs at the molecular or submolecular scale, via classical reversible receptor–ligand interactions, and can lead to a response with great sensitivity and speed. Remarkably, recognition is coupled to memory, such that responses are modulated by events which occurred years or even decades before. Although the immune system in general responds differently and more vigorously to stimuli entering the body from the outside (e.g. infections), this is an emergent property of the system: many of the recognition molecules themselves have no inherent bias towards external stimuli (non-self) but also bind targets found within the body (self). It is quite clear that the immune response registers pathophysiological changes in general. Cancer, wounding and chronic tissue injury are some obvious examples. Against this background, the immune system ‘state’ tracks the internal processes of the body, and is likely to encode information regarding both current and past disease processes. Moreover, the distributed nature of most immune responses (e.g. typically involving lymphoid tissue, non-lymphoid tissue, bone marrow, blood, extracellular interstitial spaces, etc.) means that many of the changes associated with immune responses are manifested systemically, and specifically can be detected in blood. This provides a very convenient route to sampling immune cells. We consider two different and complementary ways of querying the human immune ‘state’ using high-dimensional genomic screening methodologies, and discuss the potentials of these approaches and some of the technological and computational challenges to be overcome. PMID:24427535

Protective immunity against Trypanosoma cruzi provided by oral immunization with Phytomonas serpens: role of nitric oxide.

PubMed

Pinge-Filho, P; Peron, J P S; de Moura, T R; Menolli, R A; Graça, V K; Estevão, D; Tadokoro, C E; Jankevicius, J V; Rizzo, L V

2005-01-31

We have previously demonstrated that Phytomonas serpens, a tomato parasite, shares antigens with Trypanosoma cruzi, the protozoa that causes Chagas' disease. These antigens are recognized by human sera and induce protective immunity in Balb/c mice. In the present study, inducible nitric oxide synthase (iNOS) knockout (KO) mice and C57BL/6 mice treated with the nitric oxide inhibitor, aminoguanidine (AG, 50 mg kg(-1)) infected with T. cruzi, were used to demonstrate the role of nitric oxide (NO) to host protection against T. cruzi infection achieved by oral immunization with live P. serpens. A reduction in parasitaemia and an increase in survival were observed in C57BL/6 infected mice and previously immunized with P. serpens, when compared to non-immunized mice. iNOS (KO) mice immunized and C57BL/6 immunized and treated with AG presented parasitaemia and mortality rates comparable to those of infected and non-immunized mice. By itself, immunization with P. serpens did not induce inflammation in the myocardium, but C57BL/6 mice so immunized showed fewer amastigotes nests in the heart following an acute T. cruzi infection than those in non-immunized mice. These results suggest that protective immunity against T. cruzi infection induced by immunization with P. serpens is dependent upon enhanced NO production during the acute phase of T. cruzi infection.

Immunity in urogenital protozoa.

PubMed

Malla, N; Goyal, K; Dhanda, R S; Yadav, M

2014-09-01

Innate and adaptive immunity play a significant role in urogenital infections. Innate immunity is provided by the epithelial cells and mucus lining along with acidic pH, which forms a strong physical barrier against the pathogens in female reproductive tract. Cells of innate immune system, antimicrobial peptides, cytokines, chemokines and adaptive immunity in the reproductive tract are evolved during infection, and a pro-inflammatory response is generated to fight against the invading pathogen Trichomonas vaginalis, a primary urogenital protozoa, the etiological agent of human trichomoniasis, a curable sexually transmitted infection. The involvement of the urogenital tract by other protozoal infections such as P. falciparum, Trypanosoma, Leishmania, Toxoplasma, Entamoeba histolytica and Acanthamoeba infection is rarely reported. Trichomonas induce pro-inflammatory and immunosuppressive responses in infected subjects. Multifactorial pathogenic mechanisms including parasite adherence, cysteine proteases, lipophosphoglycan, free radical, cytokine generation and Toll-like receptors appear to interplay with the induction of local and systemic immune responses that ultimately determine the outcome of the infection. However, the involvement of urogenital pathogen-specific immune mechanisms and effect of normal local resident flora on the outcome (symptomatic vs. asymptomatic) of infection are poorly understood. Moreover, immune interactions in trichomoniasis subjects co-infected with bacterial and viral pathogens need to be elucidated. © 2014 John Wiley & Sons Ltd.

Rapid Link of Innate Immune Signal to Adaptive Immunity by Brain–Fat Axis

PubMed Central

Kim, Min Soo; Yan, Jingqi; Wu, Wenhe; Zhang, Guo; Zhang, Yalin; Cai, Dongsheng

2015-01-01

Innate immunity signals induced by pathogen/damage-associated molecular patterns are essential for adaptive immune responses, but it is unclear if the brain plays a role in this process. Here we show that while tumor necrosis factor (TNF) quickly increased in the brain of mice following bacterial infection, intra-brain TNF delivery mimicked bacterial infection to rapidly increase peripheral lymphocytes, especially in the spleen and fat. Multiple mouse models revealed that hypothalamic responses to TNF were accountable for this increase of peripheral lymphocytes in response to bacterial infection. Finally, hypothalamic induction of lipolysis was found to mediate the brain's action in promoting this increase in peripheral adaptive immune response. Thus, the brain-fat axis is important for rapidly linking innate immunity to adaptive immunity. PMID:25848866

Is there still an immunity gap in high-level national immunization coverage, Iran?

PubMed

Zahraei, Seyed Mohsen; Eshrati, Babak; Gouya, Mohammad Mehdi; Mohammadbeigi, Abolfazl; Kamran, Aziz

2014-10-01

As there is a significant number of Iranian immigrant and illegal refugees living in marginal areas of large cities that might induce immunization gap in these areas.  The aim of this study was to provide reliable information on vaccination status of these people. A cross sectional study was conducted on children 24-47 month old who lived in the suburb areas of five large cities of Iran in 2013. Proportional cluster sampling method was used in each city and standard questionnaire of the World Health Organization applied for the purpose of data collection. The survey counts immunizations based on immunization card plus the history of vaccination according to the mother's memory. All gathered data were analyzed using SPSS software (version 16). Overall, 4502 children (49.2% female) aged 24-47 month participated in this survey among which 88.1% were Iranian and 11.9% were Afghan or other nationalities. Totally, 4479 (99.4%, CI 95%: 99.2%-99.6%) of the children had a vaccination card while 828 (18.5%, CI 95%; 15.8%-21.1%) could not present it to the interviewers. 96.8% of children were fully immunized, 3.2% were partially immunized and 0.1% were not immunized. There was no significant difference in terms of vaccine coverage among males and females. The prevalence of partially immunization in non-Iranian children was six fold of Iranian children (11.9% vs. 2%). Immunization program is implemented appropriately with high coverage rates in suburb areas of the country. However, there is still an immunity gap in non-Iranian immigrants, which should be a health system considered as a high-risk group by the health system.

Neural circuitry and immunity

PubMed Central

Pavlov, Valentin A.; Tracey, Kevin J.

2015-01-01

Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine. PMID:26512000

Immune-related neurological toxicities among solid tumor patients treated with immune checkpoint inhibitors: a systematic review.

PubMed

Eltobgy, Mostafa; Oweira, Hani; Petrausch, Ulf; Helbling, Daniel; Schmidt, Jan; Mehrabi, Arianeb; Schöb, Othmar; Giryes, Anwar; Decker, Michael; Abdel-Rahman, Omar

2017-07-01

Immune-related neurologic toxicities are uncommon but serious adverse events that may be associated with the use of immune checkpoint inhibitors. The objective of this review is to assess the incidence and risk of neurologic toxicities which are potentially immune-related and occur with immune checkpoint treatment of solid tumors. Areas covered: PubMed database has been searched till January 2017. Clinical trials, case series and case reports reporting the occurrence of immune-related neurologic toxicities in solid tumor patients treated with immune checkpoint inhibitors were included. Eighteen trials with 4469 participants were included. The most common neurologic toxicities reported with these agents included sensory and motor peripheral neuropathies. Moreover, 17 case reports describing immune-related neurological events occurring with 22 patients were included. Expert commentary: Immune-related neurological toxicities occur uncommonly in cancer patients treated immune checkpoint inhibitors. Further studies are needed to better describe the course of these events (i.e. time to onset, time to resolution and responsiveness to different immunosuppressives).

False contraindications to childhood immunization.

PubMed Central

Kinder, J; Teare, L; Rao, M; Bridgman, G; Kurian, A

1992-01-01

An immunization advisory clinic was set up in mid-Essex in 1988 to provide a referral facility for professionals and parents who were unsure about the eligibility of certain children to receive immunization. This paper describes four typical cases. The history and management of each case are described and the fact that all the children were successfully immunized is highlighted. It is hoped that by sharing the experiences of the immunization advisory clinic with other professional staff, more positive decisions regarding immunizations will be made. PMID:1586553

False contraindications to childhood immunization.

PubMed

Kinder, J; Teare, L; Rao, M; Bridgman, G; Kurian, A

1992-04-01

An immunization advisory clinic was set up in mid-Essex in 1988 to provide a referral facility for professionals and parents who were unsure about the eligibility of certain children to receive immunization. This paper describes four typical cases. The history and management of each case are described and the fact that all the children were successfully immunized is highlighted. It is hoped that by sharing the experiences of the immunization advisory clinic with other professional staff, more positive decisions regarding immunizations will be made.

The discontinuity theory of immunity

PubMed Central

Pradeu, Thomas; Vivier, Eric

2017-01-01

Some biological systems detect the rate of change in a stimulus rather than the stimulus itself only. We suggest that the immune system works in this way. According to the discontinuity theory of immunity, the immune system responds to sudden changes in antigenic stimulation and is rendered tolerant by slow or continuous stimulation. This basic principle, which is supported by recent data on immune checkpoints in viral infections, cancers, and allergies, can be seen as a unifying framework for diverse immune responses. PMID:28239677

The Immune System Game

ERIC Educational Resources Information Center

Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

2015-01-01

We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

Arkansas community pharmacists' opinions on providing immunizations.

PubMed

Pace, Anne C; Flowers, Schwanda K; Hastings, Jan K

2010-10-01

To determine community pharmacists' attitudes and knowledge on providing immunizations including perceived barriers to immunizing. The study also examined the percentage of Arkansas pharmacists providing immunizations and the utilization of student pharmacists. Survey. Arkansas community pharmacies from February to March 2009. Community pharmacists. Mailed survey. Perceived barriers to providing immunizations, pharmacists' attitudes regarding immunizations, number of immunization-certified pharmacists, immunization administration rates within the last year, and senior student pharmacists utilization. A total of 350 surveys were mailed, and 129 were returned. In all, 79% of the respondents believed administering immunizations has advanced or significantly advanced the profession. Being certified and attitude toward providing immunizations were correlated; 37% of the respondents held certification to immunize, of which 77% reported immunizing within the last year. Commonly reported barriers included time (76%) followed by reimbursement and legal liability. Only half the respondents realized fourth year student pharmacists could immunize and only 33% of certified pharmacists utilized student pharmacists to immunize. Pharmacists perceive many barriers to providing immunizations. Training student pharmacists to give immunizations may not result in them providing immunizations upon graduation. Additional education on overcoming potential barriers and using senior student pharmacists to administer immunizations is needed.

A peptide derived from enzymatic digestion of globulins from amaranth shows strong affinity binding to the replication origin of Tomato yellow leaf curl virus reducing viral replication in Nicotiana benthamiana.

PubMed

Mendoza-Figueroa, J S; Kvarnheden, A; Méndez-Lozano, J; Rodríguez-Negrete, E-A; Arreguín-Espinosa de Los Monteros, R; Soriano-García, M

2018-02-01

Tomato yellow leaf curl virus (TYLCV; genus Begomovirus; family Geminiviridae) infects mainly plants of the family Solanaceae, and the infection induces curling and chlorosis of leaves, dwarfing of the whole plant, and reduced fruit production. Alternatives for direct control of TYLCV and other geminiviruses have been reported, for example, the use of esterified whey proteins, peptide aptamer libraries or artificial zinc finger proteins. The two latter alternatives affect directly the replication of TYLCV as well as of other geminiviruses because the replication structures and sequences are highly conserved within this virus family. Because peptides and proteins offer a potential solution for virus replication control, in this study we show the isolation, biochemical characterization and antiviral activity of a peptide derived from globulins of amaranth seeds (Amaranthus hypochondriacus) that binds to the replication origin sequence (OriRep) of TYLCV and affects viral replication with a consequent reduction of disease symptoms in Nicotiana benthamiana. Aromatic peptides obtained from papain digests of extracted globulins and albumins of amaranth were tested by intrinsic fluorescent titration and localized surface resonance plasmon to analyze their binding affinity to OriRep of TYLCV. The peptide AmPep1 (molecular weight 2.076 KDa) showed the highest affinity value (Kd = 1.8 nM) for OriRep. This peptide shares a high amino acid similarity with a part of an amaranth 11S globulin, and the strong affinity of AmPep1 could be explained by the presence of tryptophan and lysine facilitating interaction with the secondary structure of OriRep. In order to evaluate the effect of the peptide on in vitro DNA synthesis, rolling circle amplification (RCA) was performed using as template DNA from plants infected with TYLCV or another begomovirus, pepper huasteco yellow vein virus (PHYVV), and adding AmPep1 peptide at different concentrations. The results showed a decrease in

Immunization alters body odor.

PubMed

Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

2014-04-10

Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

Immune dysfunction in cirrhosis

PubMed Central

Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

2014-01-01

Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

Immune dysfunction in cirrhosis.

PubMed

Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

2014-03-14

Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality.

Child Indicators: Immunization of Young Children.

ERIC Educational Resources Information Center

Lewit, Eugene M.; Mullahy, John

1994-01-01

Focuses on the immunization status of children aged 19 to 35 months. Recommended immunizations are described and contrasted with the actual status of immunization. In response to unacceptably low levels of immunization among very young children, the government is aiming at 90% immunization by the year 2000. (SLD)

Male pregnancy and biparental immune priming.

PubMed

Roth, Olivia; Klein, Verena; Beemelmanns, Anne; Scharsack, Jörn P; Reusch, Thorsten B H

2012-12-01

In vertebrates, maternal transfer of immunity via the eggs or placenta provides offspring with crucial information on prevailing pathogens and parasites. Males contribute little to such transgenerational immune priming, either because they do not share the environment and parasite pressure of the offspring or because sperm are too small for transfer of immunity. In the teleost group of Syngnathids (pipefish, seahorses, and sea dragons), males brood female eggs in a placenta-like structure. Such sex-role-reversed species provide a unique opportunity to test for adaptive plasticity in immune transfer. Here, males and females should both influence offspring immunity. We experimentally tested paternal effects on offspring immunity by examining immune cell proliferation and immune gene expression. Maternal and paternal bacterial exposure induced offspring immune defense 5 weeks after hatching, and this effect persisted in 4-month-old offspring. For several offspring immune traits, double parental exposure (maternal and paternal) enhanced the response, whereas for another group of immune traits, the transgenerational induction already took place if only one parent was exposed. Our study shows that sex role reversal in connection with male pregnancy opens the door for biparental influences on offspring immunity and may represent an additional advantage for the evolution of male pregnancy.

Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

PubMed

Fazio, V M; Ria, F; Franco, E; Rosati, P; Cannelli, G; Signori, E; Parrella, P; Zaratti, L; Iannace, E; Monego, G; Blogna, S; Fioretti, D; Iurescia, S; Filippetti, R; Rinaldi, M

2004-03-01

Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

[Effect of vitamine A on mice immune response induced by specific periodontal pathogenic bacteria-immunization].

PubMed

Lin, Xiao-Ping; Zhou, Xiao-Jia; Liu, Hong-Li; DU, Li-Li; Toshihisa, Kawai

2010-12-01

The aim of this study was to investigate the effect of vitamine-A deficiency on the induction of specific periodontal pathogenic bacteria A. actinomycetetemcomitans(Aa) immunization. BALB/c mice were fed with vitamine A-depleted diet or control regular diet throughout the whole experiment period. After 2 weeks, immunized formalin-killed Aa to build immunized models, 6 weeks later, sacrificed to determine specific antibody-IgG, IgM and sub-class IgG antibody titers in serum, and concentration of IL-10, IFN-γ, TNF-α and RANKL in T cell supernatant were measured by ELISA and T cell proliferation was measured by cintilography. SPSS 11.5 software package was used for statistical analysis. The levels of whole IgG and IgM antibody which were immunized by Aa significantly elevated, non-immune group was unable to produce any antibody. Compared with Aa immunized+RD group, the level of whole IgG in Aa immunized+VAD group was significantly higher (P<0.05); The levels of IgG2a increased obviously, whereas the levels of IgG1 subtype antibody conspicuous decreased, with a significant difference (P<0.05). Aa immunized group could induce body to produce a strong specific T-cell immune response, but Aa immunized+VAD group had a higher T cell proliferate response compared with Aa immunized+RD group, with a statistically significant difference (P<0.05); The expression of RANKL, IFN-γ and TNF-α supernatant increased, while the expression of IL-10 decreased (P<0.05). The lack of vitamin-A diet can increase the immunized mice's susceptibility to periodontal pathogenic bacteria and trigger or aggravate immune inflammatory response. Adequate vitamin A is an important factor in maintaining body health. Supported by Natural Science Foundation of Liaoning Province (Grant No.20092139) and Science and Technology Program of Shenyang Municipality (Grant No.F10-149-9-32).

Management of the Critically Ill Marrow Transplant Patient

DTIC Science & Technology

1988-01-01

dose-limiting factor diation (TBI) on serum amylase. Total serum amylase (21, 81). In addition, in allogeneic (non-self) was measured on 30 patients...refractory lo other Iherapy. By Polyclonal immune serum globulin (ISC) or nature of the production process, however. antilymphocyte immuioglobulin (ALG) anti...8217 .tients by giving CMV-negative blood products struction of lymphocytes. In severe cases, hy- and by avoiding the use of CMV-positive mar- potension

Varicella Zoster Virus (Chickenpox) Infection in Pregnancy

PubMed Central

Lamont, Ronald F.; Sobel, Jack D; Carrington, D; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Vaisbuch, Edi; Romero, Roberto

2011-01-01

Congenital varicella syndrome, maternal varicella zoster virus pneumonia and neonatal varicella infection are associated with serious feto-maternal morbidity and not infrequently with mortality. Vaccination against Varicella zoster virus can prevent the disease and outbreak control limits the exposure of pregnant women to the infectious agent. Maternal varicella zoster immune globulin (VZIG) administration before rash development, with or without antivirals medications can modify progression of the disease. PMID:21585641

Self-eating and self-defense: autophagy controls innate immunity and adaptive immunity.

PubMed

Liu, Guangwei; Bi, Yujing; Wang, Ruoning; Wang, Xianghui

2013-04-01

Autophagy (macroautophagy; "self-eating") is a degradation process, in which cytoplasmic content is engulfed and degraded by the lysosome. And, immunity is an important mechanism of the "self-defense" system. Autophagy has long been recognized as a stress response to nutrient deprivation. This will provide energy and anabolic building blocks to maintain cellular bioenergetic homeostasis. Thus, autophagy plays critical roles in regulating a wide variety of pathophysiological processes, including tumorigenesis, embryo development, tissue remodeling, and most recently, immunity. The latter shows that a self-eating (autophagy) process could regulate a self-defense (immune) system. In this review, we summarize the recent findings regarding the regulatory and mechanistic insights of the autophagy pathway in immunity.

Agouron and immune response to commercialize remune immune-based treatment.

PubMed

James, J S

1998-06-19

Agouron Pharmaceuticals agreed in June to collaborate with The Immune Response Corporation on the final development and marketing of an immune-based treatment for HIV. Remune, the vaccine developed by Dr. Jonas Salk, is currently in Phase III randomized trials with 2,500 patients, and the trials are expected to be completed in April 1999. Immune-based treatments have been difficult to test, as there is no surrogate marker, like viral load, to determine if the drug is working. Agouron agreed to participate in the joint venture after reviewing encouraging results from preliminary trials in which remune was taken in combination with highly active antiretroviral drugs.

The Scaffold Immune Microenvironment: Biomaterial-Mediated Immune Polarization in Traumatic and Nontraumatic Applications.

PubMed

Sadtler, Kaitlyn; Allen, Brian W; Estrellas, Kenneth; Housseau, Franck; Pardoll, Drew M; Elisseeff, Jennifer H

2017-10-01

The immune system mediates tissue growth and homeostasis and is the first responder to injury or biomaterial implantation. Recently, it has been appreciated that immune cells play a critical role in wound healing and tissue repair and should thus be considered potentially beneficial, particularly in the context of scaffolds for regenerative medicine. In this study, we present a flow cytometric analysis of cellular recruitment to tissue-derived extracellular matrix scaffolds, where we quantitatively describe the infiltration and polarization of several immune subtypes, including macrophages, dendritic cells, neutrophils, monocytes, T cells, and B cells. We define a specific scaffold-associated macrophage (SAM) that expresses CD11b + F4/80 + CD11c +/- CD206 hi CD86 + MHCII + that are characteristic of an M2-like cell (CD206 hi ) with high antigen presentation capabilities (MHCII + ). Adaptive immune cells tightly regulate the phenotype of a mature SAM. These studies provide a foundation for detailed characterization of the scaffold immune microenvironment of a given biomaterial scaffold to determine the effect of scaffold changes on immune response and subsequent therapeutic outcome of that material.

A plant effector-triggered immunity signaling sector is inhibited by pattern-triggered immunity.

PubMed

Hatsugai, Noriyuki; Igarashi, Daisuke; Mase, Keisuke; Lu, You; Tsuda, Yayoi; Chakravarthy, Suma; Wei, Hai-Lei; Foley, Joseph W; Collmer, Alan; Glazebrook, Jane; Katagiri, Fumiaki

2017-09-15

Since signaling machineries for two modes of plant-induced immunity, pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), extensively overlap, PTI and ETI signaling likely interact. In an Arabidopsis quadruple mutant, in which four major sectors of the signaling network, jasmonate, ethylene, PAD4, and salicylate, are disabled, the hypersensitive response (HR) typical of ETI is abolished when the Pseudomonas syringae effector AvrRpt2 is bacterially delivered but is intact when AvrRpt2 is directly expressed in planta These observations led us to discovery of a network-buffered signaling mechanism that mediates HR signaling and is strongly inhibited by PTI signaling. We named this mechanism the ETI-Mediating and PTI-Inhibited Sector (EMPIS). The signaling kinetics of EMPIS explain apparently different plant genetic requirements for ETI triggered by different effectors without postulating different signaling machineries. The properties of EMPIS suggest that information about efficacy of the early immune response is fed back to the immune signaling network, modulating its activity and limiting the fitness cost of unnecessary immune responses. © 2017 The Authors.

Pharmacists as immunizers: a survey of community pharmacists' willingness to administer adult immunizations.

PubMed

Edwards, Nicholas; Gorman Corsten, Erin; Kiberd, Mathew; Bowles, Susan; Isenor, Jennifer; Slayter, Kathryn; McNeil, Shelly

2015-04-01

Adult immunization rates worldwide fall below desired targets. Pharmacists are highly accessible healthcare providers with the potential to increase immunization rates among adults by administering vaccines in their practice setting. To determine the attitudes of community-based Canadian pharmacists with respect to expanding their scope of practice to include administration of immunizations. An internet-based survey was emailed to community pharmacists across Canada. The survey was piloted through focus groups for qualitative feedback, tested for content validity, and test-retest reliability prior to dissemination. There were 495 responses to the survey. The majority (88 %) agreed that pharmacists as immunizers would increase public access, improve rates (84 %), and be acceptable to the public (72 %). However, only 68 % agreed that pharmacists should be permitted to immunize. The majority of respondents (90 %) agreed that certification in vaccine administration should be required for pharmacists to administer vaccines. Pharmacists identified education, reimbursement, and negative interactions with other providers as barriers to pharmacists administering vaccines. Canadian pharmacists are willing to expand their scope of practice to include immunization. However, implementation requires professional development and certification in vaccine administration.

Insect Immunity to Entomopathogenic Fungi.

PubMed

Lu, H-L; St Leger, R J

2016-01-01

The study of infection and immunity in insects has achieved considerable prominence with the appreciation that their host defense mechanisms share many fundamental characteristics with the innate immune system of vertebrates. Studies on the highly tractable model organism Drosophila in particular have led to a detailed understanding of conserved innate immunity networks, such as Toll. However, most of these studies have used opportunistic human pathogens and may not have revealed specialized immune strategies that have arisen through evolutionary arms races with natural insect pathogens. Fungi are the commonest natural insect pathogens, and in this review, we focus on studies using Metarhizium and Beauveria spp. that have addressed immune system function and pathogen virulence via behavioral avoidance, the use of physical barriers, and the activation of local and systemic immune responses. In particular, we highlight studies on the evolutionary genetics of insect immunity and discuss insect-pathogen coevolution. Copyright © 2016 Elsevier Inc. All rights reserved.

The National Immunization Information Hotline.

PubMed

Gust, D A; Gangarosa, P; Hibbs, B; Wilkins, C; Ford, K; Stuart, M; Brown-Bryant, R; Wallach, G; Chen, R T

2004-01-01

The National Immunization Information Hotline (NIIH) has been providing information regarding immunizations to the public and to health care professionals since March 1997. We describe the operations of the NIIH, its experience over the first two and a half years of operation and lessons learned for other immunization hotlines. From 1998-2000, the hotline answered 246,859 calls. Calls concerning immunization information requests totaled 175,367; data about the calls were collected from 35,102. Approximately a third of the 35,102 calls were from health care providers. Of the remaining calls from the public, the greatest number of calls concerned childhood immunizations. Immunization schedule queries from the public increased 323.0% from 1998 to 2000. While the major goal of the NIIH is to provide accurate and reliable information to the public and to health care providers, data from the hotline can be used to monitor changes over time in calls concerning inquiries about the immunization schedule in addition to other variables of interest.

Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices.

PubMed

Manning, Susan E; Rupprecht, Charles E; Fishbein, Daniel; Hanlon, Cathleen A; Lumlertdacha, Boonlert; Guerra, Marta; Meltzer, Martin I; Dhankhar, Praveen; Vaidya, Sagar A; Jenkins, Suzanne R; Sun, Benjamin; Hull, Harry F

2008-05-23

These recommendations of the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations on human rabies prevention (CDC. Human rabies prevention--United States, 1999: recommendations of the Advisory Committee on Immunization Practices. MMWR 1999;48 [No. RR-1]) and reflect the status of rabies and antirabies biologics in the United States. This statement 1) provides updated information on human and animal rabies epidemiology; 2) summarizes the evidence regarding the effectiveness/efficacy, immunogenicity, and safety of rabies biologics; 3) presents new information on the cost-effectiveness of rabies postexposure prophylaxis; 4) presents recommendations for rabies postexposure and pre-exposure prophylaxis; and 5) presents information regarding treatment considerations for human rabies patients. These recommendations involve no substantial changes to the recommended approach for rabies postexposure or pre-exposure prophylaxis. ACIP recommends that prophylaxis for the prevention of rabies in humans exposed to rabies virus should include prompt and thorough wound cleansing followed by passive rabies immunization with human rabies immune globulin (HRIG) and vaccination with a cell culture rabies vaccine. For persons who have never been vaccinated against rabies, postexposure antirabies vaccination should always include administration of both passive antibody (HRIG) and vaccine (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]). Persons who have ever previously received complete vaccination regimens (pre-exposure or postexposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have previously had a documented rabies virus neutralizing antibody titer should receive only 2 doses of vaccine: one on day 0 (as soon as the exposure is recognized and administration of vaccine can be arranged) and the second on day 3. HRIG is administered only once (i.e., at the beginning

Proteomic Analysis of Albumins and Globulins from Wheat Variety Chinese Spring and Its Fine Deletion Line 3BS-8

PubMed Central

Ma, Chao-Ying; Gao, Li-Yan; Li, Ning; Li, Xiao-Hui; Ma, Wu-Jun; Appels, Rudi; Yan, Yue-Ming

2012-01-01

The relationship between chromosome deletion in wheat and protein expression were investigated using Chinese Spring and fine deletion line 3BS-8. Through 2-DE (2-D electrophoresis) analysis, no differentially expressed proteins (DEPs) were found in leaf samples; however, 47 DEPs showed at least two-fold abundance variation (p < 0.05) in matured wheat grains and 21 spots were identified by tandem MALDI-TOF/TOF-MS. Among the identified spots, four were cultivar-specific, including three (spots B15, B16, and B21) in Chinese Spring and one in 3BS-8 (spot B10). Among variety-different DEPs between Chinese Spring and 3BS-8, most spots showed a higher express profile in CS; only four spots showed up-regulated expression tendency in 3BS-8. An interesting observation was that more than half of the identified protein spots were involved in storage proteins, of which 11 spots were identified as globulins. According to these results, we can presume that the encoded genes of protein spots B15, B16, and B21 were located on the chromosome segment deleted in 3BS-8. PMID:23202959

Immune System Dysfunction in the Elderly.

PubMed

Fuentes, Eduardo; Fuentes, Manuel; Alarcón, Marcelo; Palomo, Iván

2017-01-01

Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

The most common friend first immunization

NASA Astrophysics Data System (ADS)

Nian, Fu-Zhong; Hu, Cha-Sheng

2016-12-01

In this paper, a standard susceptible-infected-recovered-susceptible(SIRS) epidemic model based on the Watts-Strogatz (WS) small-world network model and the Barabsi-Albert (BA) scale-free network model is established, and a new immunization scheme — “the most common friend first immunization” is proposed, in which the most common friend’s node is described as being the first immune on the second layer protection of complex networks. The propagation situations of three different immunization schemes — random immunization, high-risk immunization, and the most common friend first immunization are studied. At the same time, the dynamic behaviors are also studied on the WS small-world and the BA scale-free network. Moreover, the analytic and simulated results indicate that the immune effect of the most common friend first immunization is better than random immunization, but slightly worse than high-risk immunization. However, high-risk immunization still has some limitations. For example, it is difficult to accurately define who a direct neighbor in the life is. Compared with the traditional immunization strategies having some shortcomings, the most common friend first immunization is effective, and it is nicely consistent with the actual situation. Project supported by the National Natural Science Foundation of China (Grant No. 61263019), the Program for International Science and Technology Cooperation Projects of Gansu Province, China (Grant No. 144WCGA166), and the Program for Longyuan Young Innovation Talents and the Doctoral Foundation of Lanzhou University of Technology, China.

[Potency testing of anti-lymphocyte Globulins: In vitro alternatives for the monkey skin-graft assay

PubMed

Conrad, Christoph; Kabelitz, Dieter; Schäffner, Gabriele

1998-01-01

Antilymphocyte globulins (ALG) are immunosuppressive agents of animal origin currently used in clinical transplantation medicine and for the treatment of severe aplastic anemia. The potency of each batch is tested in vivo using primates as hosts for allogeneic skin transplantation. The test is done with a maximum of three animals, one as a control and two after the treatment with ALG. The two in vitro methods in use are a cytotoxic assay and the rosette inhibition assay. These methods are evaluated with the microscope. Besides wellfare aspects these methods require a lot of experience, are subjective, difficult to validate and the information about the biological potency of the sera is questionable. The aim of our study is a better biological characterisation as a prerequisite to subsequently define an in vitro alternative for the potency test in monkeys. Using a competition assay with monoclonal antibodies we can identify several specificities directed against functional molecules on T cells (e.g., CD2, CD3, CD5, CD28), B Cells (CD19), macrophages and natural killer cells (CD16) and nonlineage specificities such as CD18, CD25, CD29, CD95. This method could describe a part of the biological potency and control homogeneity of batches. The cytotoxic capacity of ALG either with or without complement as well as DNA-fragmentation characteristic for apoptosis can be analysed by flowcytometry using propidiumiodide- (PI) incorporation. Immunoprecipitation of cell-lysate with ALG