Serum Protein Electrophoresis in Tuberculosis

Serial serum protein electrophoretic determinations at two-month intervals were carried out on 84 tuberculous patients undergoing treatment in a sanatorium. An attempt was made to correlate changes in the albumin/alpha-2 globulin ratios and gamma globulin levels with clinical and roentgenographic status. It was observed that before treatment of the tuberculous process the albumin/alpha-2 globulin ratios were low and the gamma globulin levels were increased. As improvement occurred, albumin/alpha-2 globulin ratios increased and gamma globulin values decreased. A poor prognosis was indicated by decreasing albumin/alpha-2 globulin ratios. Electrophoretograms are of particular value in assessing the effect of surgery, especially when roentgenographic studies are not informative. They are also a valuable guide in deciding upon the duration of therapy necessary for individual cases.     

The Metabolism of Serum Proteins in the Hen and Chick and Secretion of Serum Proteins by the Ovary of the Hen

In the chicken, serum gamma globulin (CGG) is preferentially transferred by the follicular epithelium of the ovary to the developing ova. The concentration of gamma globulin in the yolk of the unfertilized egg is many times the concentration of chicken serum albumin (CSA). This transfer occurs largely during the 4 to 5 days preceding ovulation when the growth of the ovum is most rapid. Thus, in the chicken, the follicular epithelium of the ovary serves the same purpose in the passive immunization of offspring as does the acinar epithelium of the udder in ungulates and the extraembryonic membranes in rabbits and man. The amount of gamma globulin synthesis by the chick is low during the first 2 weeks of life and is associated with low levels of serum gamma globulin. By the end of the 1st month of life, the level of serum gamma globulin increases, presumably reflecting an increased rate of synthesis. In the adult hens the half-life of I¹³¹-labeled CSA is 66 hours and that of I¹³¹-labeled CGG, 35 hours, while in the newly hatched chick for I¹³¹-labeled CSA it is 42 hours and for I¹³¹-labeled CGG, 72 hours. Thus, this species shows a gamma globulin sparing in the first days of life, as do most mammalian species.     

The effect of human gamma globulin on tbe production of antibodies to the surface antigen of the hepatitis B virus in an experiment on animals

The biological assay for the determination of HBsAg in gamma globulin is proposed. The assay is based on the immunizing action of immune complexes and some specific features of secondary immune response. For this purpose, the highly purified preparation of HBsAg is injected into guinea pigs. Subsequently the animals receive human gamma globulin. An increase in the titer of anti-HBsAg antibodies in the animals preimmunized with the antigen is indicative of the presence HBsAg in human gamma globulin. In accordance with another variant of this assay, human gamma globulin is introduced into mice and 21 days later the animals are immunized with HBsAg. The appearance of anti-HBsAg antibodies in the animals, previously treated with gamma globulin, on day 4 after the injection of the antigen indicate that the animals experience the second penetration of HBsAg, i. e. its presence in previously injected human gamma globulin.     

Plasma protein regulation of platelet function and metabolism

Summary This reviews summarizes our evidence suggesting that the plasma protein environment influences platelet aggregation potential and metabolic activity.Cationic proteins are capable of restoring the aggregation potential of washed human platelets. The aggregation restoring effect of gamma globulin is inhibited by more anionic proteins in subfractions of Cohn fraction IV and fractions V and VI. Artificial enhancement of the net negative charge of plasma proteins through acylation produces derivatives capable of inhibiting platelet aggregation in platelet rich plasma.The oxygen consumption of washed human platelets is lower than in platelet rich plasma while the lactate production is identical. Autologous plasma, albumin or IgG immunoglobulin restores the oxygen consumption of washed platelets to values comparable to those obtained for platelet rich plasma, while the lactate production is unaffected. Fibrinogen or IgA myeloma protein increases the lactate production, but not the oxygen consumption. Cyclic AMP levels are considerably lower in washed platelets than in platelet rich plasma. Gamma globulin and albumin causes a further decrease, which is progressive with time. Fibrinogen causes no change in platelet cyclic AMP content.It is suggested that these observations may in part be explained by the equilibrium between anionic and cationic proteins in the platelet microenvironment.This hypothesis appears applicable in certain clinical situations.     

Locomotion and adhesion of neutrophil granulocytes : Effects of albumin, fibrinogen and gamma globulins studied by reflection contrast microscopy

Proteins as well as materials of low molecular weight have marked effects on the rate of locomotion, adhesion and cell shape of human neutrophil granulocytes in vitro. Plasma protein preparations differ qualitatively with respect to their chemokinetic activity. Human serum albumin (HSA), fibrinogen and acid-treated gamma globulin without polymers have a positive chemokinetic effect on neutrophils suspended in Gey's solution. Standard gamma globulin (SGG) or acid-treated gamma globulin with polymers have marked negative chemokinetic activity. Three different mechanisms are presumably responsible for the low rate of locomotion observed in Gey's solution alone, Gey's solution containing acid-treated gamma globulin with polymers or SGG, respectively: (a) too firm adhesion to the substratum; (b) lack of adhesion to the substratum; and (c) impaired capacity to perform shape changes. The relationship between attachment of cells to the substratum and the rate of neutrophil locomotion has been investigated. It appears that the pattern of adhesion rather than cell attachment as measured by the proportion of neutrophils adhering to the substratum is a meaningful correlate to locomotion. Two different patterns of adhesion can be distinguished by means of reflection-contrast microscopy: (a) the pattern characterized by uniform grey areas is compatible with efficient locomotion; (b) a pattern characterized by large black areas at the cell periphery. It is associated with neutrophils in Gey's solution which fail to displace themselves efficiently. This suggests that reflection-contrast microscopy may be helpful in distinguishing contacts allowing locomotion to occur from contacts impeding neutrophil locomotion.     

The cellular biology of megakaryocytes

Megakaryocytes show a pattern of cellular proliferation and maturation which is unique in mammalian biology. Cells mature to the point of cytoplasmic fragmentation in three major ploidy classes, 8n, 16n, and 32n and the three are fed from a precursor committed stem cell. Two-thirds of the cells belong in the 16n class, and approximately one-sixth in the 8n and 32n classes. The cytoplasm of cells in each ploidy class has a characteristic concentration of granules and demarcation membrane system which appears to be translated into the characteristic features of the platelet progeny from each class. These differ from normal young platelets. Megakaryocytes release fragments of cytoplasm into marrow sinusoids and these differ from platelets in that they do not have the peripheral microtubular bundle or sub-marginal dense tubular system. Transition from fragment to circulating platelet presumably takes place elsewhere in the circulation. With stimulation of platelet production, "stress" platelets are produced, from megakaryocytes which show changes with respect to content of polyribosomes, glycogen and membrane.     

Platelet activation induces increased Fc gamma receptor expression

Platelet contain Fc gamma RII. However, little is known about how the expression of these receptors is regulated. Inasmuch as platelet activation by a variety of agonists increases the expression of several proteins on the platelet surface, we used flow cytometry to study the effect of platelet activation on the expression of platelet Fc gamma R by measuring the binding of fluorescein-labeled oligomeric IgG (FITC-IgG oligomer) and fluorescein-labeled mAb IV.3 (FITC-IV.3), a mAb that recognizes Fc gamma RII, to platelets. The number of Fc gamma R per platelet was determined by relating the binding to platelets of FITC-IV.3, measured by flow cytometry, to the binding of 125I-labeled IV.3, measured using a standard filtration assay. Nonactivated, gel-filtered platelets from nine healthy donors expressed a mean of 891 Fc gamma R per platelet, whereas platelets activated at 25 degrees C by thrombin or PMA expressed a mean of 1382 Fc gamma R an average increase of 55% (p less than 0.001). Binding of FITC-IgG oligomer increased to a similar extent when platelets were stimulated by these agonists. A smaller increase in the number of Fc gamma R expressed on the platelet surface was measured when platelets were stimulated with ADP, though no increase was observed with epinephrine. The agonist-dependent increase in Fc gamma R expression did not occur when platelets were studied at 4 degrees C or in the presence of agents that elevate intracellular levels of cAMP, suggesting that platelet activation was required for this process. Agonist-stimulated Fc gamma R expression did not depend on dense-granule secretion, because it was observed at low agonist concentrations in the absence of 14C-serotonin release. These studies demonstrate that the number of Fc gamma R expressed on the platelet surface increases when platelets are activated by several agonists, perhaps as a result of the exposure of Fc gamma R located along the surface-connected open canalicular system, or the fusion of platelet alpha-granule and plasma membranes during the activation process. Increased Fc gamma R expression may promote the clearance of IgG-containing immune complexes from the circulation, and contribute to the development of immune complex-mediated thrombocytopenia.     

Development and trial of a heterogenous antistaphylococcal gamma-globulin

Antitoxic and antibacterial equine gamma globulin for the treatment of staphylococcal infection has been developed and introduced into medical practice. The pronounced effectiveness of the preparation has been demonstrated in comparison with the ineffectiveness of traditional therapeutic measures. The development of mild forms of the serum disease in 33% of cases indicates that further investigations on the purification of gamma globulin preparations are necessary.     

Prevention of infections hepatitis by gamma globulin

Infectious hepatitis, a viral disease, has become increasingly more important in recent years. It is believed that the great increase in reported cases is not due entirely to better reporting, but that there has been an actual increase in the incidence of this disease. The comparatively long incubation period in infectious hepatitis, the high incidence in persons in close contact with patients who have the disease, and the fact that in most instances contact between persons is the mode of spread, makes this disease particularly suitable for the use of an immunizing agent which would be administered after exposure. From the studies reviewed it is apparent that gamma globulin is of value in preventing hepatitis both when administered as mass prophylaxis in an epidemic, and when given to persons in close contact with a person who has the disease. Widespread use of gamma globulin prophylactically among persons who have been in close contact with the occasional patients with infectious hepatitis seen by practicing physicians might often obviate the need for mass immunization. It should be stated that there is little evidence for the effectiveness of gamma globulin in the therapy of infectious hepatitis. In a study in which very large amounts (average dose 45 cc.) of gamma globulin were given very early in the disease, no significant difference was observed between those injected and a control group.     

PREVENTION OF INFECTIOUS HEPATITIS BY GAMMA GLOBULIN

Infectious hepatitis, a viral disease, has become increasingly more important in recent years. It is believed that the great increase in reported cases is not due entirely to better reporting, but that there has been an actual increase in the incidence of this disease. The comparatively long incubation period in infectious hepatitis, the high incidence in persons in close contact with patients who have the disease, and the fact that in most instances contact between persons is the mode of spread, makes this disease particularly suitable for the use of an immunizing agent which would be administered after exposure.From the studies reviewed it is apparent that gamma globulin is of value in preventing hepatitis both when administered as mass prophylaxis in an epidemic, and when given to persons in close contact with a person who has the disease. Widespread use of gamma globulin prophylactically among persons who have been in close contact with the occasional patients with infectious hepatitis seen by practicing physicians might often obviate the need for mass immunization. It should be stated that there is little evidence for the effectiveness of gamma globulin in the therapy of infectious hepatitis. In a study in which very large amounts (average dose 45 cc.) of gamma globulin were given very early in the disease, no significant difference was observed between those injected and a control group.     

Effect of multiple gamma globulin administration on the effectiveness of seroprophylaxis in hepatitis A

The data provided by immunological and epidemiological studies carried out to determine the influence of the multiple injections of 10% commercial gamma globulin on the level of antigamma globulin formation and, in this connection, on the effectiveness of the prophylaxis of hepatitis A are discussed. A sharp increase in the titers of antigamma globulin in persons receiving multiple gamma globulin injections is shown. The increased amount of antibodies to gamma globulin, appearing as the result of the multiple use of this preparation, decreases the effectiveness of the seroprophylaxis of hepatitis A.     

Development of resistance in rabbits to immature stages of the Ixodid tick Rhipicephalus appendiculatus

A study of acquired resistance in rabbits to larvae and nymphs of Rhipicephalus appendiculatus Neumann showed a positive correlation between the levels of gamma globulin in the serum and the resistance developed by the host. A negative correlation between the weight of engorged ticks and gamma globulin levels was also demonstrated during this study. Repeated infestations with ticks evoked a typical antibody response to antigenic challenge. The levels of gamma globulin stabilized after three infestations and no further decrease in the weight of ticks was observed. The mechanism of the acquisition of resistance by the rabbits, the production of antibodies and the involvement of complement are discussed.     

Characterization of the Fc gamma receptor on human platelets

IgG-containing immune complexes may play a role in the immune destruction of human platelets by interacting with an Fc gamma receptor on the platelet surface. We studied the platelet Fc gamma receptor and characterized its interaction with IgG ligand and anti-Fc gamma receptor monoclonal antibodies. Oligomers of IgG, but not monomeric IgG, bound to platelets and the number of binding sites was significantly increased at low ionic strength. Ligand-binding studies indicated that normal human platelets express a single Fc gamma receptor (Fc gamma RII) with 8559 +/- 852 sites per cell, Kd = 12.5 +/- 1.7 X 10(-8) M using trimeric IgG. Results of studies with bivalent and Fab monoclonal anti-Fc gamma RII were consistent with each Fc gamma receptor expressing two epitopes recognized by the antibody. The number of Fc gamma binding sites and affinity of binding were unchanged by the presence of 2.0 mM Mg2+ or 10 micrograms/ml cytochalasin B. Platelet stimulation with thrombin or ADP in the presence of fibrinogen also did not alter the number of Fc gamma binding sites or the affinity of binding. However, platelets preincubated with 5 microM dexamethasone expressed a decreased number of Fc gamma binding sites as well as decreased IgG-dependent platelet aggregation. Platelets from patients with Glanzmann's thrombasthenia and from patients with the Bernard Soulier syndrome expressed a normal number and affinity of Fc gamma binding sites. The data suggest that platelet Fc gamma RII binding of trimeric IgG occurs independent of actin filament interaction, Mg2+, ADP, or thrombin and does not require GPIIb/IIIa or GPIIb/IIIa-fibrinogen interaction. Furthermore, this receptor appears to be normally expressed on GPIb-deficient platelets and susceptible to modulation by glucocorticoids. Finally, the Fc gamma-binding protein was isolated from whole platelets as a 220-kDa protein which upon reduction dissociates into 50,000 Mr subunits.     

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

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.     

Evaluation of the prophylactic effect of gamma globulin in meningococcal infection.

Results of two controlled epidemiological tests evaluating the prophylactic effect of gamma globulin of Monogolian and Soviet production against meningococcal infection are presented. Observations were carried out on children aged 3 months to 4 years, not attending children's establishments. The results of the observation revealed the following prophylactic effect of gamma globulin of Mongolian production in the first two months after administration: index of efficiency--5.0, coefficient of efficiency--80%, P greater than 0.01. The efficiency of the prophylactic effect of Soviet gamma globulin was limited to one month: the index of efficiency amounted to 5.3, the coefficient of efficiency to 82.2%, P greater than 0.01. The course of meningococcal infection in the children who had received gamma globulin was less severe than in the children of the control group. Lethal outcome was recorded only in the group of children who had not received gamma globulin. The duration of the prophylactic effect of gamma globulin was found to depend on the height of the titres of specific antibodies in the preparation. The preparations are recommended as prophylactic means for children aged from 3 months to 4 years in doses of 1.5 ml (one dose) in the foci of meningococcal infection.     

Specificity of peroxidase-labeled antibodies to rabbit, mouse and human immunoglobulins

The comparative study of different types of conjugates (antirabbit, antimouse and antihuman) has shown that gamma globulin fractions actively interact not only with homologous peroxidase-labelled antibodies, but also with heterologous ones. Cross reactions were most pronounced between antimouse conjugates and the preparations of human gamma globulin and, vice versa, between antihuman conjugate and mouse gamma globulin. The study has shown that the main cause of cross reactions is the presence of common antigenic determinants in the preparations of mouse and human gamma globulin.     

Labeling of human IgG with rhodium-105 using a new pentadentate bifunctional ligand

We report the labeling of human gamma globulin with the 105Rh complex of a new pentadentate bifunctional ligand, 1,7-bis(2-hydroxybenzyl)-4-(p-aminobenzyl)diethylenetriamine. Complexes of this ligand with 105Rh were prepared by refluxing rhodium carrier spiked with 105Rh at pH9 in bicarbonate buffer. The complex was treated with an excess concentration of thiophosgene to prepare the isothiocyanate derivative which was extracted into CHCl3. The CHCl3 extract was dried and dissolved in DMF and reacted with a borate solution of human gamma globulin. Labeling yields were generally high and varied from 73% to 93%, depending upon the concentration of human gamma globulin and the isothiocyanate derivative of the complex used. The overall recovery of rhodium activity varied from 59% to 75% without taking into account activity lost due to decay. The conjugation reaction was complete by 4 h. From 0.4 to 8.5 atoms of Rh could be incorporated per molecule of protein by this method. The activated isothiocyanate complex did not show any degradation when stored at room temperature for up to 4 days and then used for conjugation.     

Antibody prophylaxis and therapy against West Nile virus infection in wild-type and immunodeficient mice

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

丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗重症手足口病患儿的临床研究

目的:探讨丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗重症手足口病(HFMD)患儿的临床效果。方法:选择我院2013年1月至2014年1月收治的重症HFMD患儿80例,按随机数字表法平均分为两组,研究组及对照组各40例。对照组患者在常规治疗基础上给予甲泼尼龙琥珀酸钠治疗,研究组患者给予丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗,比较两组患儿治疗疗效,发热、疱疹、神经系统受累症状消退时间及住院时间。结果:研究组患儿治疗总有效率为97.5%,明显高于对照组87.5%,比较差异具有统计学意义(x2=3.85,P0.05)。研究组患儿发热消退时间、疱疹消退时间、神经系统受累症状消退时间及住院时间均明显短于对照组,比较差异具有统计学意义(均P0.05)。结论:丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗重症HFMD患儿疗效显著,可有效改善患儿临床症状,值得临床推广应用。     

The Metabolism of Serum Proteins in Neonatal Rabbits

1. Incorporation of S³⁵-labeled amino acids into serum proteins has been studied in neonatal and developing rabbits. It was found that, per unit weight, neonatal rabbits synthesized only about 1/36 of the gamma globulin, 1/7 of the beta globulin, ½ of the alpha globulin, and ⅛ of the albumin that an adult synthesized. The growing rabbit developed the ability to synthesize various serum proteins at different times. 2. Plasma volumes and serum protein concentrations were determined at different times during the growth period of the rabbit. Plasma volumes were found to be 1 and ½ times larger in newborn animals than in adults, with a gradual decline to the adult level. The total serum protein concentration at birth was about 60 to 65 per cent of the adult value and gradually increased with growth as the plasma volume decreased. 3. Half-lives of homologous albumin and gamma globulin were studied. The half-life of albumin in neonates was nearly twice as long as the half-life in adults, the latter value being reached at 1 month of age. The half-life of gamma globulin in neonates was more than twice as long as the half-life in adults and reached adult values at 2 to 3 months. 4. Attempts were made to alter serum protein metabolism. Gamma globulin synthesis early in life was augmented with antigen injections.