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The interaction mechanism of spherical gold nanoparticles (AuNPs) and rod-shaped gold nanoparticles (AuNRs) with γ-globulin and hemoglobin was comprehensively and comparatively analyzed. γ-Globulin and hemoglobin have high affinity with AuNPs, and with two different types of binding sites on AuNRs surface. Except hemoglobin interaction with the first binding site of AuNRs, the interaction between γ-globulin/hemoglobin and AuNPs/AuNRs is the spontaneous, endothermic and entropy-driven process, and hydrophobic interaction plays a dominant role. The molecular adsorption mechanism of γ-globulin/hemoglobin on AuNPs and AuNRs surface conforms to Langmuir model and Freundlich model, respectively. The kinetic molecular mechanism between them conforms to the pseudo-second-order model, and chemisorption is the rate-limiting step. AuNPs result in the loosening and unfolding of γ-globulin backbone. AuNRs have no significant effect on γ-globulin backbone. AuNPs/AuNRs result in no significant changes in hemoglobin structure and heme group microenvironment. AuNPs/AuNRs decrease the hydrophobicity of Trp microenvironment of γ-globulin, but there is an intramolecular energy transfer from Trp residue to Tyr residue of hemoglobin. The β-sheet of γ-globulin and the α-helix of hemoglobin reduce by increasing concentrations of AuNPs/AuNRs. Molecular docking is suggesting that the specific amino acid residues of γ-globulin and hemoglobin interaction with AuNPs/AuNRs, and validates the experimental results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The pattern of serum proteins, the typical features of the electrophoretogram in newborn piglets and during their postnatal development is not completely described. Therefore, the aim of this study was to characterize the changes in serum protein electrophoretic pattern and features of the electrophoretograms during the early postnatal period. Significant changes during the monitored period were found in all evaluated parameters (P < 0.001). The most marked changes were observed mainly in the period before weaning. The concentrations of total proteins, albumin and γ-globulins were before colostrum intake low, γ-globulins represented the smallest proportion of protein fractions. The proportion of α 1 -globulins was after birth a dominant protein fraction. Significant increase of total proteins, α 2 -, β- and γ-globulins and decrease of α 1 -globulins was found 2 days after colostrum intake. The albumin and A/G values increased after birth gradually until weaning. After weaning a significant changes were found in absolute concentrations of total protein and albumin, and in relative values of β-globulin fractions. Presented results showed marked developmental alterations in the serum protein pattern in piglets along with the age. The study also brings new knowledge in the field of description of typical features of electrophoretograms in the observed period of piglet's life., (© 2021. The Author(s).)

Patients with haematological malignancies are considered to be a risk group for developing severe Coronavirus disease (Covid-19). Because of the limitations of therapeutic options, the development of new treatment strategies is mandatory, such as convalescent plasma (CP). Herein we report the use of CP therapy as an off-label indication in two lymphoma patients with relapsed COVID-19 in the setting of low gammaglobulin levels because of previous rituximab chemo-immunotherapy. Both were PCR positive for SARS-CoV-2 but had an absence of antibodies to the virus more than one month later of symptoms initiation. They developed important respiratory and neurological complications. After CP infusion, neutralising antibodies were detected and viral load dissapeared in both patients leading to clinical improvement with no more Covid-19 relapse., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Dogs are the main reservoir hosts of Leishmania infantum; nevertheless, recent investigations indicate a likely role for cats in the epidemiology of Leishmania infection. Feline leishmaniosis (FeL) remains poorly characterised, partly due to the lack of suitable diagnostic tools. This study aimed to compare serum amyloid A (SAA) levels and serum protein electrophoresis (SPE) profiles (specifically, alpha 2 and gamma globulins) in cats naturally exposed to or infected by L. infantum from southern Italy versus those of healthy controls and versus cats with neoplastic or inflammatory conditions from non-endemic areas., Methods: Serum or plasma samples from four cohorts of cats were analysed for SAA levels and by SPE: (i) G1: healthy controls from Leishmania-non-endemic regions of Switzerland; (ii) G2: cats pre-diagnosed with neoplastic or inflammatory conditions available from the University of Cambridge sample archive; (iii) G3: L. infantum-seropositive, quantitative (q)PCR-negative cats from southern Italy; (iv) G4: L. infantum-seropositive and qPCR-positive cats from southern Italy. SAA data were assessed for normality and homoscedasticity using the Shapiro-Wilk and Levene's tests, respectively; the Kruskall-Wallis test, followed by Dunn's test with Bonferroni correction were subsequently used to compare SAA serum levels between groups. A weighted generalised linear model with a binomial distribution was used to assess statistically significant differences in the numbers of animals displaying elevated gamma globulins and increased alpha 2 globulins between groups., Results: Overall, 68 samples were analysed (G1: n = 16, G2: n = 20, G3: n = 20, G4: n = 12). Cats suffering from neoplastic and inflammatory conditions (G2 ) showed significantly higher SAA levels than healthy controls (G1) (median values [interquartile range]: G1: 0.00 [0.00-0.00] mg/l versus G2: 0.85 [0.00-49.55] mg/l). G2, G3 and G4 cats showed higher percentages of individuals with increased alpha 2 globulins (percentages ± standard error: G1 = 20.0% ± 10.3, G2 = 80.0% ± 8.9, G3 = 70.0% ± 10.2, G4 = 75.0% ± 12.5) and gamma globulins (G1 = 0.0% ± 0, G2 = 65.0% ± 10.7, G3 = 50.0% ± 11.2, G4 = 58.3% ± 14.2) than healthy control cats (G1). For all three markers, no significant difference between cats within G2, G3 and G4 was recorded., Conclusions: This study indicates that the proportions of animals with elevated levels of alpha 2 and gamma globulins are significantly higher in cats exposed to and infected with L. infantum. Levels of SAA and alpha 2 and gamma globulins may not be used to differentiate between L. infantum infection or exposure, and neoplastic and/or inflammatory conditions.

Exploration of simple and universal methods to quantitatively measure nanoparticle (NP)-protein interaction is of great importance. In this work, pulsed streaming potential (SP) measurement has been used to evaluate the interaction between NPs and proteins within microchannels. Graphene oxide (GO) and SiO 2 NPs were selected to represent two kinds of NPs. Lysozyme and common blood proteins, including albumin V, γ-globulins, and fibrinogen, were used as model proteins. The linear relationship between the initial adsorption rate ( S = d E r /d t ) and the concentration of proteins was observed. Combined with the Hill equation, the microscopic dissociation constant ( K D ) and the Hill coefficient ( n ) between NPs and proteins were calculated based on the relationship between S and the concentration of each protein. The concentration of free proteins which have not interacted with the NPs in the NPs-protein mixture could also be measured. The influence of pH, conductivity, and ionic strengths of the incubation buffer on the interaction between GO and lysozyme was evaluated based on the constant K D . The interaction intensity between NPs and proteins was defined as charge neutralization efficiency Q C , which could be calculated from the value of S . It takes only 150 s to get the whole set of data under the optimized experiment parameters. The measurement solely depends on the surface charge, no intrinsic fluorescence is required for either the NPs or the proteins, and no labeling or immobilization process is involved as well.

Background: Loss of response to anti-TNFα treatment occurs frequently in IBD- patients. We evaluatedthe predictive value of serum albumin and γ-globulin concentrations for treatment failure., Methods: Prospectively, all patients treated for the first time with either infliximab or adalimumab for IBD between 2007 and 2018 were included. All patients were tested for serum albumin and γ-globulin concentrations and were followed up until June 2018., Results: 128 patients (95 Crohn's disease, 67 females, age 40.1 ± 13.7 years) were included in the study. 81patients (63.3%) received infliximab and 47 (36.7%) adalimumab first line. Eight patients (6.3%) were primary non-responders, 50 patients (39.0%) showed a sustained clinical remission and 70 patients (54.7%) developed a secondary loss of response. Meantime to develop secondary loss of response was 24.5 ± 20.5 months. Albumin serum concentrations in the clinical response group were significantly higher than in the secondary loss of response group (39.8 ± 5.7 g/L vs. 35.0 ± 5.4 g/L). γ-globulin serum concentrations in the sustained response group were significantly lower than in the secondary loss of response group (11.8 ± 2.8 g/L vs. 14.7 ± 4.5 g/L). Hypoalbuminemia and hypergammaglobulinemia were associated with the loss of response. Immunosuppressant co-medication in patients with high γ-globulin serum concentrations reduced the risk of secondary loss of response., Conclusion: Low albumin and increased γ-globulin serum concentrations are strongly associated with a higher risk for loss of response to an anti-TNFα treatment. Increased serum γ-globulin concentrations may have a higher risk to produce anti-drug antibodies or a different phenotype of disease less responsive to anti-TNFα treatment.

Objective: To determine altered manifestation of plasma proteins in X-rays technicians who are regularly exposed to low doses of radiations over a long period during their job., Study Design: Descriptive study., Place and Duration of Study: District Headquarters Hospital and Mufti Mahmood Memorial Teaching Hospital; from January 2017 to January 2018., Methodology: The study enrolled 70 individuals consisting of 50 X-ray technicians working 8 to 12 hours/day for five days per week and 20 unexposed healthy controls. The serum protein expression pattern (concentrations of various serum proteins) was evaluated through cellulose acetate electrophoresis and serum antioxidant status was measured through ferric reducing ability of plasma (FRAP) assay., Results: The antioxidant assay showed significantly low trolox-equivalent antioxidant capacity (TEAC) status and FRAP value in X-ray technicians as compared to controls (p<0.001). Analysis of serum protein demonstrated a significantly reduced concentrations of albumin (p<0.001) and elevated level of the Ɣ-globulins (p<0.001), while other globulins fractions like α1 and β remain unchanged. There was a strong negative correlation (p<0.001) according to Pearson coefficient (r=87%⁽⁻⁾) between albumin and Ɣ-globulins fraction. Whereas, a positive correlation (p<0.001) (r=46%⁽⁺⁾) between alpha 1 globulin and albumin fraction was observed. A correlation between other globulin fractions and albumin was found statistically significant (p<0.001)., Conclusion: Elevated serum gamma globulins may be a potential protein biomarker for triage and detection of X-radiation induced damages.

Objective: The production of antibody, also referred immunoglobulin, is the principal functions of B cells. Gamma globulin fraction determined by serum protein electrophoresis is composed almost entirely of immunoglobulin. This study aimed to investigate the association between gamma globulin level and oncological outcomes in patients with nonmuscle-invasive bladder cancer (NMIBC)., Patients and Methods: A total of 274 patients with NMIBC who underwent transurethral surgery between 2000 and 2015 were identified. One hundred forty-four patients (52.6%) had received adjuvant intravesical bacillus Calmette-Guérin. Gamma globulin fraction (%) was determined by serum protein electrophoresis, and gamma globulin level (mg/dl) was calculated by multiplying the total protein level (mg/dl) by the gamma globulin fraction (%). The association between gamma globulin levels and oncological outcomes was statistically evaluated., Results: During a median follow-up period of 39 months, 99 (36.1%) patients experienced at least 1 tumor recurrence and 16 (5.8%) patients had disease progression. The median (interquartile range) gamma globulin level was 1.2 (1.0-1.3) mg/dl. Recurrence-free survival rate of patients with gamma globulin levels of ≥1.4 mg/dl was significant lower than that of patients with gamma globulin levels of <1.4 mg/dl (P < 0.01). There was no significant difference in progression-free survival between the 2 groups (P = 0.17). Multivariate analysis revealed that gamma globulin level of ≥1.4 mg/dl is significantly associated with higher recurrence rate (hazard ratio = 1.83, P < 0.01)., Conclusion: Gamma globulin level is significantly associated with tumor recurrence. Our results suggest that B cell immunity may be involved in tumor recurrence in patients with NMIBC., (Copyright © 2019. Published by Elsevier Inc.)

Background: Despite the development of early detection methods and new antiviral drugs, cytomegalovirus (CMV) infection remains a persistent and sometimes severe complication of stem cell transplantation (SCT). CMV antigenemia has become widely used for early detection of CMV infection after SCT., Procedure: We retrospectively analyzed risk factors for CMV antigenemia in pediatric patients following allogeneic SCT. We analyzed 74 pediatric patients who received allogeneic SCT at Sapporo Hokuyu Hospital between April 2007 and March 2018 and were alive over three months after SCT., Results: Of the 74 patients, 22 (29.7%) were CMV antigenemia positive. On univariate analyses, many patients with CMV antigenemia tested positive for CMV antibody before SCT (P < 0.001), and had lower gamma globulin levels before conditioning (P = 0.014). Multivariate analysis additionally confirmed that pre-SCT CMV antibody positivity (P < 0.001) and preconditioning gamma globulin levels under 655 mg/dL (P = 0.004) were independent risk factors for post-SCT CMV antigenemia., Conclusions: These results indicate the importance of assessing gamma globulin levels in pediatric patients prior to SCT., (© 2018 Wiley Periodicals, Inc.)

This study reports on the real-time binding assessment between heavy metal ions and blood proteins immobilized onto nanoporous anodic alumina photonic crystals (NAA-PCs) by reflectometric interference spectroscopy (RIfS). The surface of NAA-PCs is chemically functionalized with γ-globulin (GG), transferrin (TFN), and serum albumin (HSA), the major proteins present in human blood plasma. Protein-modified NAA-PC platforms are exposed to analytical solutions of mercury ions of different concentrations. Dynamic changes in the effective optical thickness of protein-modified NAA-PCs in response to heavy metal ions are assessed in real time to evaluate the binding kinetics, affinity, and mechanism. Protein molecules undergo conformational changes upon exposure to mercury ions, with HSA exhibiting the strongest affinity. The combination of protein-modified NAA-PCs with RIfS allows real-time monitoring of protein-heavy metal ions interactions under dynamic flow conditions. This system is capable of detecting dynamic conformational changes in these proteins upon exposure to heavy metal ions. Our results provide new insights into these binding events, which could enable new methodologies to study the toxicity of heavy metal ions and other biomolecular interactions.

Objectives: To evaluate the levels of the serum gamma globulin fraction in proteinograms as a biomarker to assess the severity, and to predict the mortality and new exacerbations in patients admitted for an exacerbation of a COPD., Patients and Methods: The VIRAE study was carried out on a cohort of patients hospitalized for an exacerbation of probable infectious origin of COPD over a period of 2 years. The levels of the serum gamma globulin fraction were analyzed in the proteinogram of 120 patients. The main clinical indicators of severity were also evaluated. Key features were compared in 2 groups (gamma fraction in the proteinogram greater or less than 6.6g/dl)., Results: The levels of the serum gamma fraction in the proteinogram correlated with the FEV 1 (P=.009), the CRP (P=.04), and the number of readmissions after 6 months of hospitalization (P=.04). We observed a good association with the GOLD scale, the BODE index and the mMRC dyspnea scale; and also with treatment with oral corticoids and home oxygen therapy. We did not find it to be a good predictor of mortality, despite observing increased mortality rates one year after hospital admission in patients with low levels of the factor., Conclusions: The levels of the gamma globulin fraction in proteinograms has a good correlation with the FEV 1 . In addition, they are associated with a greater severity of patients with COPD. This simple biomarker may be useful in identifying high-risk patients., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

We report the development of thermoresponsive 4-mercaptoethylpyridine (MEP)-based chromatographic microsphere based resins for antibody separation that show switchable release abilities by adsorbing immunoglobulins at 40 °C and releasing the proteins at 5 °C. The thermoswitchable release properties were introduced to the porous resins by the grafting of linear poly(N-isopropylacrylamide) (PNIPAM) chains synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, which were modified to possess MEP end functionalities. Adsorption of γ-globulins as a model antibody on the shortest PNIPAM-MEP (3 kDa) grafted microparticles display binding capacities of up to 20 g L(-1) at 40 °C and a significant decrease in binding capacity to less than 2.5 g L(-1) at 5 °C. By switching the temperature to 5 °C, the release of bound γ-globulins is shown to be as high as 90%. The effects of polymer chain length on the binding capacity are studied in detail and found to be critical as they influence the density of MEP functionalities on the particle surfaces.

Biocompatibility of nanoparticles depends on their binding behavior with biomolecules. Herein, we have reported the interaction of three different biological macromolecules such as hemoglobin, gamma globulin and transferrin with hydroxyl group functionalized Multi-Walled Carbon Nanotubes (OH-MWCNTs). Multiple spectroscopic methods were utilized to identify the binding cum structural changes in biomolecules upon their interaction. Hyperchromic effect observed in the UV-visible spectra, and the quenching behavior from fluorescence emission evidences the existence of bio-nanotube complex formation. Synchronous and three-dimensional fluorescence spectra of biomolecules, in correspondence with Trp and Tyr residues showed the possible disturbance towards their aromatic micro-environment. Changes observed in the FTIR and FT-Raman amide bands, and amino acid residue position of biomolecules upon interaction with CNTs showed the possible effect towards their secondary structure. Further studies with CD spectroscopy indicated the loss of alpha-helical structures quantitatively. The study remains significant in evaluating the biosafety profile of functionalized MWCNTs for their in vivo biomedical applications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: Hepatitis A virus (HAV) infection tends to be a self-limiting disease without serious sequelae, but fulminant hepatitis, with a high mortality, develops in 0.1-0.2% of the cases. Sometimes, HAV infection precipitates autoimmune hepatitis (AIH). We aimed to assess the frequency and clinical significance of serologic markers of autoimmunity during hepatitis A infection with an acute or fulminant presentation compared with those in AIH., Methods: The study included 126 children: 46 with HAV infection (33 with acute and 13 with fulminant presentation), 53 with AIH, and 27 healthy controls. In all, we measured autoantibodies titer (antinuclear antibody, antismooth muscle antibody, and liver kidney microsomal antibody-1) and serum gammaglobulins., Results: Autoantibodies were detected in the majority of HAV (63.1%) and AIH (79.2%) groups, but in none of the controls. Gammaglobulins were significantly higher in the HAV group (1.93±0.57 g/dl) than in the controls (1.32±0.29 g/dl), but lower than that in the AIH group (2.93±1.2 g/dl) (P<0.0001 for all). In the HAV group, gammaglobulins were significantly higher in those with fulminant (2.21±0.46 g/dl) than in those with acute presentation (1.82±0.57 g/dl) (P=0.019), but comparable with that in AIH (P=0.095). Gammaglobulins correlated significantly with disease severity in both HAV and AIH groups., Conclusion: Hypergammaglobulinemia and a high occurrence of autoantibodies are encountered in HAV infection. This may support the immunological basis of its pathogenesis. Moreover, the higher gammaglobulins in fulminant HAV, with an insignificant difference from that in AIH, suggest that a more aggressive immunological reaction is related to this presentation.

Autonomous self-propelled catalytic microjets are envisaged as an important technology in biomedical applications, including drug delivery, micro/nanosurgery, and active dynamic bioassays. The direct in vivo application of these microjets, specifically in blood, is however impeded by insufficient knowledge on the in vivo viability of the technique. This study highlights the effect of blood proteins on the viability of the microjets. The presence of blood proteins, including serum albumin and γ-globulins at physiological concentrations, has been found to dramatically reduce the viability of the microjets. The reduction of viability has been measured in terms of a lower number of active microjets and a decrease in the velocity of propulsion. It is clear from this study that in order for microjets to function in biomedical applications, different modes of propulsion besides platinum-catalyzed oxygen bubble ejection must be employed. These findings have serious implications for the biomedical applications of catalytic microjets., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

As a model for understanding how molecular crowding influences diffusion and transport of proteins in cellular environments, we combined experimental and theoretical approaches to study the diffusion of proteins in highly concentrated protein solutions. Bovine serum albumin and γ-Globulin were chosen as molecular crowders and as tracers. These two proteins are representatives of the main types of plasma protein and have different shapes and sizes. Solutions consisting of one or both proteins were studied. The self-diffusion coefficients of the fluorescently labeled tracer proteins were measured by means of fluorescence correlation spectroscopy at a total protein concentration of up to 400 g/L. γ-Globulin is found to have a stronger influence as a crowder on the tracer self-diffusion coefficient than Bovine serum albumin. Brownian dynamics simulations show that the excluded volume and the shape of the crowding protein have a significantly stronger influence on translational and rotational diffusion coefficients, as well as transient oligomerization, than hydrodynamic or direct interactions. Anomalous subdiffusion, which is not observed at the experimental fluorescence correlation spectroscopy timescales (>100 μs), appears only at very short timescales (<1 μs) in the simulations due to steric effects of the proteins. We envision that the combined experimental and computational approach employed here can be developed to unravel the different biophysical contributions to protein motion and interaction in cellular environments by systematically varying protein properties such as molecular weight, size, shape, and electrostatic interactions., (Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes formed by them with human serum γ-globulin induce the production of early (24-h incubation) IL-1β by human blood cells. The protein modified by Zn cations 1.2 times more actively (p<0.01) induced early IL-1β than the control γ-globulin, while γ-globulin metal complex with copper was 1.4 times less active (p<0.1) than the control protein. The regularities of induction changed over the course of 48-h incubation: zinc cations chelated by γ-globulin fraction protein reduced, while copper cations stimulated the realization of the protein induction potential in the metal complex.

Serum protein electrophoresis is widely used in clinical laboratories to measure the relative abundance of each obtained fraction. Moreover, we found that the migration time of the γ-globulin fraction can be reproducibly determined (CV = 1.1%). Immunoglobulins were purified from serum using protein L-agarose and their N-glycosylation was studied using CE on a DNA sequencer. Liver fibrosis patients showed a lower level of sialylation and this moderately correlates with the migration time of the γ-globulins (r = 0.2-0.4). This allowed us to differentiate healthy individuals from these patients with an acceptable diagnostic accuracy (area under the curve = 0.75). This glycomics approach could become a significant added value to a daily, routine clinical test.

Objective: Rituximab seems well tolerated in patients with rheumatoid arthritis (RA). However, variations in the gammaglobulin profile that might increase the infection risk have been reported. Here, our objective was to evaluate gammaglobulin concentrations and the infection risk in patients receiving rituximab therapy for RA in everyday practice., Methods: Prospective single-center observational study of 65 patients with refractory RA (median age, 59 years; range, 26-83) treated with rituximab 1 g twice 15 days apart, with or without a further 1-g dose at least 6 months later depending on the clinical response. Gammaglobulins were assayed before each rituximab dose., Results: The median cumulative rituximab dose was 4 g (1-16) and the median time to retreatment was 8 months (6-16). Rituximab therapy significantly improved the DAS-28 score. The gammaglobulin concentration decreased significantly between the first and last rituximab dose (from 11.6 g/L [5-26] to 8.2 g/L [3-20], a -2.6 g/L difference; P<0.05). The decrease was larger in the 24 patients with cumulative rituximab doses greater than 5 g than in the 41 other patients (difference of -4 vs. -2.7 g/L; P<0.05). Three patients experienced severe infections, two in the high-dose group and one in the other group (P=0.5)., Conclusion: These data obtained in everyday practice constitute further evidence that rituximab is well-tolerated in patients with RA. Rituximab therapy was associated with a decrease in gammaglobulin concentrations that was greater in patients receiving higher cumulative doses., (Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

In relation to the interplay between C-reactive protein (CRP) and its various ligands, including extracellular matrix proteins or plasma proteins, herein we compared the effectiveness of modified CRP (mCRP) in modulation of platelet function under different experimental conditions. mCRP (100 μg/ml) was significantly more effective in stimulation of platelet activation when measured in suspensions of isolated platelets than in whole blood (fraction of CD62-positive platelets was 73.4 ± 5.3 vs. 0.8 ± 1.0% in isolated platelets and 7.0 ± 1.8 vs. 1.3 ± 0.4% in whole blood). Platelet adhesion to fibrinogen was almost seven-fold higher in suspensions of isolated platelets compared to platelet-rich plasma (PRP) (P < 0.005). Furthermore, mCRP enhanced platelet aggregation in a whole blood but it had no effect in PRP. The effectiveness of mCRP in stimulation of platelet response in plasma has been associated with the proportions of gamma globulin and albumin in human serum (rp = 0.78, P < 0.0001 for gamma globulin and Rp = -0.52, P = 0.02 for albumin concentrations; for albumin/gamma globulin ratio rp = -0.72, P < 0.0005). Such associations have been further confirmed by experiments showing that mCRP interacts with some immunoglobulins. Taken together, the modulation of platelet function by mCRP seems to be strongly determined by the presence of the gamma globulin fraction in platelet milieu.

Purpose: The aim of the present study was to gain insight into the penetration, biodistribution, and fate of globulins in the brain after 2-O-hexyldiglycerol-induced blood-brain barrier opening., Procedures: The spatial distribution of fluorescence probes was investigated after blood-brain barrier opening with intracarotid 2-O-hexyldiglycerol injection. Fluorescence intensity was visualized by microscopy (mice and rats) and by in vivo time-domain optical imaging., Results: There was an increased 2-O-hexyldiglycerol-mediated transfer of fluorescence-labeled globulins into the ipsilateral hemisphere. Sequential in vivo measurements revealed that the increase in protein concentration lasted at least 96 h after administration. Ex vivo detection of tissue fluorescence confirmed the results obtained in vivo., Conclusion: Globulins enter the healthy brain in conjunction with 2-O-hexyldiglycerol. Sequential in vivo near-infrared fluorescence measurements enable the visualization of the spatial distribution of antibodies in the brain of living small animals.

Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes they form with human serum γ-globulin induce the production of IFN-α by human blood cells throughout the periods of up to 72 h. Zinc cation-modified protein by 1.6 times (p<0.05) more actively induces late IFN-α than the control γ-globulin; γ-globulin-copper metal complex is 2-fold (p<0.002) more effective than the control protein. The results indicate that functional relationships between the components inducing the production of late IFN-α differ from the effects realized during the early period of induction.

Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes formed by these cations and human serum γ-globulin induce blast transformation of splenocytes from BALB/c mice at a level comparable to that induced by concanavalin A. Zinc bound to γ-globulin reduces by 25% and copper in complex with this protein stimulates by 1.6 times its capacity to induce blast transformation. Combinations with concanavalin A reproduce the effects of γ-globulin-metal complex under conditions of mitogen induction. Incorporation of(3)H-thymidine in splenocytes incubated with combinations of γ-globulin-copper metalcomplex, copper cations, and control protein with concanavalin A was by 1.4, 1.3 (p<0.1), and 1.25 times higher (p<0.05), respectively, than after incubation with concanavalin A alone.

The molecular property-affinity relationship of dietary flavonoids for bovine gamma-globulin (γ-globulin) was investigated by fluorescence titration analysis. The quenching effects of flavonoids on γ-globulin fluorescence depended on the structures of flavonoids. The magnitudes of binding constants between flavonoids and γ-globulin were within the range of 10(3)-10(5) L mol(-1). These data were much smaller than the affinities between flavonoids and purified bovine and human serum albumins. The affinities of flavonoids for γ-globulin were strongly influenced by the structural differences of the compounds under study. The affinities for γ-globulin decreased with increasing partition coefficients and increased with increasing hydrogen bond acceptor numbers of flavonoids, which suggested that the binding interaction was mainly caused by hydrogen bond forces.

Objectives: To determine the capacity of human serum proteins to bind to titanium dioxide (TiO(2)) particles of different polymorphs and sizes., Methods: TiO(2) particles were mixed with diluted human serum, purified human serum albumin (HSA) or purified human serum gamma-globulin (HGG) solutions. After incubation at 37°C for 1 h, the particles were sedimented by centrifugation, and proteins in the supernatant, as well as those bound to the particles, were analyzed., Results: The total protein concentration in the supernatant was lowered by TiO(2), whereas the albumin/globulin ratio was elevated by the particles. Incubation with TiO(2) also lowered the immunoglobulin, pre-albumin, beta2-microglobulin, ceruloplasmin and retinol-binding protein levels, but not ferritin levels, in the supernatant. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), proteins in the supernatant, especially HGG, were observed to decrease, while those released from the particles (after adding 1% SDS and heating) increased, depending on the dose of TiO(2). Purified HGG and HSA were also bound to TiO(2), although the former appeared to have a higher affinity. All the proteins tested showed the highest binding potency to the amorphous particles (<50 nm) and the lowest to the rutile particles (<5,000 nm), while binding to anatase particles was intermediate. The affinity to the larger anatase was higher than that to smaller anatase particles in most cases., Conclusions: Human serum proteins, including the two major components, HSA and HGG, are bound by TiO(2) particles. The polymorph of the particles seems to be important for determining the binding capacity of the particles and it may affect distribution of the particles in the body.

The mechanisms by which proteins adsorb to surfaces of biomaterials have long been of interest. The present work started with the premise that small/hard and large/soft proteins will yield different sets of normalized frequency shift and dissipation signals when studied with a quartz crystal microbalance. The aim was to evaluate the usefulness of these raw data to study protein competition using protein incubations in sequence and from mixtures of albumin (BSA) and gamma-globulin (BGG) at various ratios. Increasing the concentration of BSA decreases the adsorption of subsequently incubated BGG. For BSA/BGG mixtures the dissipation is similar for all logarithmic molar ratios BGG/BSA below 1 but soon decreases when the molar ratio of BSA/BGG (and opposite for the normalized frequency shift) is above 1, indicating preferential binding of BGG. Modelling indicated that differences in the film shear modulus and viscosity depend more on the properties of the self-assembling mono-layers (SAMs) than on the proteins. Films high in BSA tentatively differ in film shear modulus and viscosity from that of films high in BGG but only on the hydrophobic surfaces. The results were encouraging as the raw data were deemed to be able to point at protein adsorption competition., (2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

A new approach has recently been proposed for the purification of 'mammalian-type' IgG, consisting of exclusion binding. The technique uses a gel ('Melon gel'; Pierce) that binds to all plasma proteins, but not to IgGs, thus allowing IgGs to be recovered in the FT (flow-through) fraction. Here, the technique was applied to camelid IgGs, which are known to be composed of not only classic mammalian-type IgGs (IgG1) but also HC-IgGs (heavy chain IgGs). Both mammalian type and HC-IgGs can be purified in the FT fraction of dromedary (Camelus dromedarius) plasma samples with less than 8.5% contamination, by making minor improvements to the conditions recommended by the manufacturer. The contaminant proteins, as determined by LC-MS/MS (liquid chromatography-tandem MS), are mainly transferrin and albumin. The recovery rate is elevated for both types of IgGs (95+/-14% and 88+/-25% for IgG1 and HC-IgGs respectively). IgGs thus purified maintain their ability to bind to their antigen, as measured by surface plasmon resonance and Western ligand blotting. Furthermore, IgGs can be purified from plasma samples of all camelid species in a similar manner, although the ratio of HC-IgGs to total IgGs was lower for Lama (llama) and Vicugna (vicuña) than for Camelus species. The 'Melon gel' technique can thus be used to satisfactorily purify IgG1 and HC-IgGs from all camelid species.

Polyclonal intravenous immunoglobulins (IVIGs) can modulate the host immune response and may improve outcomes in some patients. In this prospective, noninterventional study, we assessed the time-course of gamma-globulin concentrations in 21 patients with septic shock and evaluated the relationship of gamma-globulin concentrations to disease severity and outcome. Six patients (28.5%) died. Sixteen patients (76%) had hypo-gamma-globulinemia at admission: 12 (57%) had low IgG concentrations (G650 mg/dL), 2 had low IgA concentrations (G70 mg/dL), and 9 had low IgM concentrations (G40 mg/dL). Two patients had low concentrations of all three gamma-globulins; these patients both died from refractory shock within 2 days. Patients with low IgG concentrations were indistinguishable at baseline from patients with normal IgG concentrations but had fewer vasopressor-free days (over 28 days) and more frequently developed acute lung injury/acute respiratory distress syndrome (3/9 vs. 10/12; P = 0.02). All deaths occurred in the patients with low IgG concentrations (6/ 12 vs. 0/9). There was a variable increase in kappa and lambda free light chains, a marker of gamma-globulin synthesis, over time with no significant difference between low and normal IgG groups. This pilot study indicates that low concentrations of gamma-globulins, especially IgG, are common in patients with community-acquired septic shock and persist over time even when sepsis resolves. Despite similar presentation, patients with hypo-IgG had greater vasopressor requirements, were more likely to develop acute lung injury/acute respiratory distress syndrome, and had higher mortality. Patients with low IgG concentrations may represent a logical target group to study the effects of Ig supplementation in septic shock.

Plasma gamma-globulin fraction proteins, copper and zinc cations, and metal-modified gamma-globulins induce the production of IFN by human leukocytes. Binding of zinc cations attenuates the realization of the IFN-inducing effects of human serum gamma-globulin, while binding of copper cations potentiated this effect. Activity of IFN and the dynamics of its production correspond to those in response to phytohemagglutinin stimulation. The pool of induced IFN contains acid-labile (up to 60%) and acid-stable (up to 40%) constituents. Anti-IFN-alpha antibodies do not modify activity of produced IFN. The results indicate the possibility of gamma-globulin conformation allowing stimulation or attenuation of the protein capacity to induce the production of IFN pool with predominant content of IFN-gamma.

Samples of human serum gamma-globulin with specifically bound copper or zinc cations were studied in Mancini's radial immunodiffusion test with human antibodies to IgG (H+L). The intensity of antibody binding to zinc-modified protein was 10-20% higher in comparison with the reference sample, while detection of gamma-globulin with bound copper by antibodies was 20-30% lower than in the corresponding reference sample. Comparison with the results of native gamma-globulin testing indicates limitations of Mancini's method as the quantitative assay for practical diagnosis, because under certain clinical conditions the traditional method can give over- and underestimated results.

The non-random association of Gaucher disease with polyclonal and monoclonal gammopathy has been known since 1950. The effect of treatment on monoclonal gammopathy is not well documented. We report on the long-term evolution of a biclonal gammopathy in a patient with type I Gaucher disease who was treated with splenectomy and enzyme replacement therapy. A 44-year-old man presented with hepatomegaly and massive splenomegaly. Bone marrow aspirate contained typical Gaucher cells and beta-glucosidase was low in peripheral blood leukocytes. Mutations N370S and R120W were detected. Serum protein electrophoresis disclosed two spikes in gammaglobulins. Immunofixation identified two monoclonal components: IgG kappa and IgA kappa. Gammaglobulin concentration was 31.6 g/L. A splenectomy was performed on September 2003 because of massive splenomegaly (9500 g). Two months after the splenectomy, gammaglobulin concentration was 25.2 g/L. Enzyme replacement therapy (Cerezyme 45 UI/kg every two weeks) was prescribed from April 2004 because of significant hepatomegaly and cholestasis. In April 2007 (3 years after the beginning of treatment), serum electrophoresis showed the persistence of two spikes with gammaglobulin concentration at 20.5 g/L. Simultaneously, chitotriosidase activity decreased from 6181 to 2877 nkat/L. Our observation and previous reports suggest that enzyme replacement therapy is more effective in polyclonal hypergammaglobulinaemia than in monoclonal gammopathy.

Samples of human serum gamma-globulin modified by equimolar binding of copper and zinc cations were obtained using the method of molecular ultrafiltration. Conformation characteristics of the protein were studied by UV spectrophotometry. Immunochemical study included radial immunodiffusion test, direct and sandwich enzyme immunoassays. Conformation changes in gamma-globulin caused by incorporation of solitary metal cations into the protein molecule modified presentation of antigenic determinants on the globule surface and their availability for recognition by specific antibodies. New antigenic determinants and new antigenic specificity of gamma-globulin are not formed under these conditions.

The histone deacetylase inhibitors (HDA-CIs) butyrate and trichostatin A activate gamma-globin expression via a p38 mitogen-activating protein kinase (MAPK)-dependent mechanism. We hypothesized that down-stream effectors of p38 MAPK, namely activating transcription factor-2 (ATF-2) and cyclic AMP response element (CRE) binding protein (CREB), are intimately involved in fetal hemoglobin induction by these agents. In this study, we observed increased ATF-2 and CREB1 phosphorylation mediated by the HDACIs in K562 cells, in conjunction with histone H4 hyperacetylation. Moreover, enhanced DNA-protein interactions occurred in the CRE in the (G)gamma-globin promoter (G-CRE) in vitro after drug treatments; subsequent chromatin immunoprecipitation assay confirmed ATF-2 and CREB1 binding to the G-CRE in vivo. Enforced expression of ATF-2 and CREB produced (G)gamma-promoter trans-activation which was abolished by a 2-base pair mutation in the putative G-CRE. The data presented herein demonstrate that gamma-gene induction by butyrate and trichostatin A involves ATF-2 and CREB1 activation via p38 MAPK signaling.

Protein composition of blood plasma was an object of investigation in 29 Russian cosmonauts flown on the MIR station from 125 to 366 days. Protein fractions were analyzed using acetate cellulose electrophoresis. Concentration of total protein was determined with the help of the biuret reaction on an automated analyzer. On the second day post flight, mean concentration of total protein and percentage of the protein fractions were equal to baseline values. In the interval between days 7 and 14 post flight, total protein was statistically reduced, alphal- N alpha2-globulins increased and y-globulin reduced, whereas albumin and beta-globulins were unchanged in the average. These results may point to development of an acute reaction in the early period of readaptation to the return from long-duration space flight.

The binding of wogonin to HGG was studied by spectroscopic method including circular dichroism (CD), fourier transformation infrared spectra (FT-IR), fluorescence spectra. The binding parameters and the thermodynamic parameters for the reaction have been calculated according to Sips method and Gibbs-Helmholtz equation, respectively, at different temperatures. AutoDock3.05 program was used to calculate the interaction modes between the drug and HGG. The Sips plots indicated that the binding of HGG to wogonin at 297, 304, 310 and 317 K is characterized by two binding sites with the average affinity constant Ko at 2.102x10(4), 2.078x10(4), 1.956x10(4) and 1.931x10(4), respectively. The binding process was exothermic, spontaneous and entropy driven, as indicated by the thermodynamic analyses, and the major part of binding energy is electrostatic interaction accompanied by hydrophobic interaction and hydrogen bond. The secondary structure compositions of free HGG and its wogonin complexes were estimated by the FT-IR spectra and the curve-fitted results of amide I band, which are in good agreement with the analyses of CD spectra. Furthermore, the average binding distance between wogonin and HGG (5.60 nm) was obtained on the basis of the theory of Förster energy transfer.

Paw use in a task consisting of the removal of a piece of adhesive paper from the snout was investigated in 80 mongrel and pure-bred domestic dogs (Canis familiaris). Population lateralisation was observed, but in opposite directions in the two sexes (animals were not desexed): males preferentially used their left paw, females their right paw. The relationship between immune function and paw preference was then investigated. Some immune parameters (total number of white blood cells including lymphocytes, granulocytes and monocytes; leukocyte formula; total proteins; gamma-globulins) were investigated in a sample of left-pawed (n = 6), right-pawed (n = 6) and ambidextrous (n = 6) dogs. The results showed that the percentage of lymphocytes was higher in left-pawed than in right-pawed and ambidextrous dogs, whereas granulocytes percentage was lower in left-pawed than in right-pawed and ambidextrous dogs. Moreover, total number of lymphocytes cells was higher in left-pawed than in right-pawed and ambidextrous dogs, whereas the number of gamma-globulins was lower in left-pawed than in right-pawed and ambidextrous dogs. These findings represent the first evidence that brain asymmetry modulates immune responses in dogs.

In rats exposed for 28 days (5 hours a day) to ozone at a concentration of 0.5 ppm and receiving alpha-tocopherol at doses of 4.5 mg/rat and 15 mg/rat, levels of acute phase proteins (APP)--C-reactive protein (CRP), ceruloplasmin (Cp), total protein, gamma-globulins, and activity of lysozyme in blood serum were studied. The assays were performed in the presence of respective control groups, i.e. rats receiving the same doses of alpha-tocopherol but not exposed to ozone, a group of animals not supplemented with vitamin but exposed to ozone, a group of animals injected with physiological fluid and a control group not subjected to any of the treatments. The study revealed that the ozone-exposed animals had an increased lysozyme activity and a decreased total protein level. However, in rats protected by alpha-tocopherol and exposed to ozone, the concentration of APP, lysozyme activity and total protein were found to be decreased. Similar relationships also occurred in animals receiving alpha-tocopherol and not exposed to ozone.

Seven commercially available colostrum replacers were tested for their ability to substitute for goat colostrum as a source of gammaglobulin for goat kids. One hundred kids were fed with goat colostrum or colostrum replacer after separation from their mothers at birth. Blood samples were taken from ten kids at birth, and from all kids at 48 hours after birth. Samples were used to measure the total protein content and gammaglobulin concentration of serum. Kids fed with goat colostrum had higher gammaglobulin concentrations than newborn kids or kids fed with replacer. For three replacers, the gammaglobulin concentrations were the same as those of newborn kids. For three other replacers, the gammablobulin concentrations were similar but higher than those of newborn kids. For one replacer, the levels of gammaglobulin were higher than those of in newborn kids and higher than those measured after feeding of the other replacers. None of the replacers was an adequate substitute for goat colostrum as a source of gammaglobulins.

A new method for evaluating the ratio of two structurally different proteins or other compounds in a mixture that does not require any preseparation steps and is based on using the aqueous two-phase partition technique is described. Mathematical analysis of the partitioning of a mixture of two solutes demonstrates its ability to quantitatively evaluate the ratio of the concentrations of the solutes in the initial mixture. It also provides the means for detecting interactions between the two solutes. Experimental results confirm the analysis to be correct for mixtures of low-molecular-weight compounds as well as for mixtures of structurally different proteins. An example of analysis of a clinically relevant mixture of two proteins-transferrin and carbohydrate-deficient transferrin-is provided. An analysis of interactions between two proteins and/or peptides is also illustrated using two examples., (Copyright 2001 Academic Press.)

The TiO2 photocatalyzed oxidation of the proteins serum albumin, ovalbumin and gamma globulin, is reported. All the amino acids were susceptible to photocatalytic oxidation. However, some were especially vulnerable. Tyrosine was particularly sensitive, as was the semiaromatic histidine, although to a lesser extent. The lack of an activating group on the aromatic ring in Phe, renders the system less amenable to degradation. The photocatalytic degradation of the aliphatic amino acids Gly and Asp, was particularly slow, like in the Fenton oxidation where production of glycine was observed during the cleavage of collagen induced by hydroxyl radicals. Intermediate degradation rate was noticed in Ser, Arg, Val, Cys and Phe.

In this study, which was performed on a Dutch dairy goat farm, several aspects of the administration of colostrum to new-born goat kids were examined. Time of colostrum administration and amount and type of colostrum administered were compared. Effectiveness was measured as total serum protein content and gamma globulin fraction. No significant differences in serum gamma globulin titre were observed between kids that received colostrum at 30 or 60-90 minutes post partum, respectively. Titres were significantly lower in kids that received 100 ml of colostrum instead of 150-200 ml. The effect of sheep colostrum replacer or cow colostrum was also examined. Gamma globulin titres were significantly high with goat colostrum than with cow colostrum or sheep colostrum replacer, and titres were higher with cow colostrum than with sheep colostrum replacer. Based on the results of this experiment, the following protocol is suggested for colostrum administration to goat kids: single administration of 150-200 ml of goat colostrum within 90 minutes of birth. Use of cow colostrum is not advised because it may lead to transmission of paratuberculosis. Use of sheep colostrum replacer as a source of passive immunity is not recommended.

In 3 female patients, aged 65, 83 and 76 years, with severe renal failure, light chain multiple myeloma was diagnosed, following a substantial delay on the part of the doctors concerned. Either the diagnosis had not suspected or the serum proteins had been misinterpreted. After a while, the first two patients declined further treatment with chemotherapy and haemodialysis, and subsequently died. The third patient attained a creatinine clearance of 20 ml/min and was subsequently treated for the multiple myeloma in the outpatients department. The absence of a paraprotein peak in the serum does not exclude the possibility of a multiple myeloma. In the case of light chain disease, the gammaglobulin region is, in fact, often empty. Treatment of multiple myeloma consists of a rapid rehydration and forced diuresis; the usefulness of plasmapheresis has not been demonstrated.

We document and evaluate a serous retinal detachment in a patient with hyperviscocity syndrome. Optical coherence tomographic images of the serous retinal detachment in a patient with hyperviscocity syndrome were correlated with slit-lamp biomicroscopic findings, fundus photographs, fluorescein angiograms, and indocyanine green angiograms. Fluorescein angiography demonstrated venous and capillary bed abnormalities but no leakage or pooling of fluorescein corresponding to the retinal pigment epithelial detachment (PED) beneath the serous retinal detachment. Indocyanine green angiogram disclosed a delay of intrachoroidal circulation. Optical coherence tomography (OCT) revealed a large retinal pigment epithelial detachment beneath the serous retinal detachment. The occult retinal PED beneath the neurosensory retinal detachment was detected only by OCT in a patient with hyperviscosity syndrome. We suggest that gamma globulin, which is the hyperviscosity material, accumulated in the subretinal pigment epithelial space and blocked the leakage or pooling of fluorescein corresponding to the retinal pigment epithelial detachment.

In the first week of the primary immune response to the (4-hydroxy-3-nitrophenyl)acetyl (NP) hapten, plasmacytic foci and germinal centers (GCs) in C57BL/6 mice are comprised of polyclonal populations of B lymphocytes bearing the lambda1 L-chain (lambda1+). The Ig H-chains of these early populations of B cells are encoded by a variety of VH and D exons undiversified by hypermutation while later, oligoclonal populations are dominated by mutated rearrangements of the VH186.2 and DFL16.1 gene segments. To assess directly Ab affinities within these defined splenic microenvironments, representative VDJ rearrangements were recovered from B cells participating in the early immune response to NP, inserted into Ig H-chain expression cassettes, and transfected into J558L (H-; lambda1+) myeloma cells. These transfectoma Abs expressed a remarkably wide range of measured affinities (Ka = 5 x 10(4)-1.3 x 10(6) M(-1)) for NP. VDJs recovered from both foci and early GCs generated comparable affinities, suggesting that initial differentiation into these compartments occurs stochastically. We conclude that Ag normally activates B cells bearing an unexpectedly wide spectrum of Ab affinities and that this initial, promiscuous clonal activation is followed by affinity-driven competition to determine survival and clonal expansion within GCs and entry into the memory and bone marrow plasmacyte compartments.

The interaction for silver (I) ion with gamma-globulin has been investigated by resonance spectroscopy. It is shown that 2 or 4 coordination species for amino acid residues of gamma-globulin with Ag (I) ion were formed and their resonance spectra appear to be different in amide bands region. It has been studied that effect of reaction time on resonance Raman(RR) spectra in heat condition. Results showed that the intensity of RR has maximum at about 15 min of reaction, and after the time, Ag (I) ion on species will reduced to elemental silver.

Effects of long-term oral administration of ginseng extract on serum protein profile and immunoglobulin (Ig) isotypes were studied in mice. Ginseng extract was orally administered to healthy female mice for 52 days at doses of 30 and 150 mg/kg per day and serum protein electrophoretograms and Ig isotypes levels were evaluated. Serum level of gamma-globulin was decreased dose dependently to 82% (P < 0.05) and 56% (P < 0.01) of control values at the doses of 30 and 150 mg/kg per day, respectively. Levels of total protein, albumin, alpha2- and beta-globulin fractions, as well as the ratio of albumin to globulin (A/G) did not change significantly. However, the alpha1-globulin level increased by 24% (P < 0.05) at the doses of 30 and 150 mg/kg per day. Among the Ig isotypes, including IgG1, IgG2a, IgG2b, IgG3, IgM and IgA, serum IgG1 was dose dependently decreased to 68% (P < 0.05) of control values at the dose of 150 mg/kg per day without significant changes in other Ig isotypes. As IgG1 isotype is rarely cytotoxic and can act as a blocking antibody, it is suggested that the selective decrease in serum IgG1 induced by ginseng extract without changes in the cytotoxic antibodies such as IgG2a may be helpful for the prevention and inhibition of cancer.