Increase In Gamma Globulin Research Articles

Familial lipochrome pigmentation of histiocytes with hyperglobulinemia, pulmonary infiltration, splenomegaly, arthritis and susceptibility to infection

Three sisters, aged twenty-six, twenty-one and sixteen, were discovered to have a similar disease characterized by lipochrome granulation of histiocytes, hyperglobulinemia, splenomegaly and pulmonary infiltrations. In addition, the twenty-six year old subject had marked susceptibility to infection, the twenty-one year old sister had transient episodes of arthritis, and the sixteen year old had juvenile rheumatoid arthritis with nodules. Histiocytes containing lipochrome-pigmented granules were found in biopsy specimens from all three girls and in the sputum of one. Rheumatoid factor was present in each girl and the serum of one, when examined by ultra-centrifugation, showed a small amount of globulin with a faster sedimentation rate than the 19S globulins. The hyperglobulinemia consisted mainly of an increase in gamma globulin but the alpha 2 globulins were also increased. No abnormalities were detected in serum lipids and no hepatic or renal dysfunction was demonstrable. Blood platelet counts were moderately elevated in the sixteen year old girl and slightly elevated in the other two. The twenty-six year old woman with a susceptibility to infections had a poor typhoid H antibody response to T.A.B. vaccination. It is hypothesized that the lipochrome granulation of the histiocytes is the basic genetic defect, the other clinical and laboratory manifestations of the syndrome being secondary.

Auto-immune thyroiditis

The study of thyroid auto-immunity is still in its early stages and much work remains to be done. Thus, it is still uncertain whether the thyroid auto-antibodies arise because of some subtle alteration in the chemical constitution of the thyroid auto-antigens, because of failure to acquire tolerance or because of some derangement of the antibody-forming mechanism which renders it incapable of recognizing self; or whether the thyroid auto-antibodies merely reflect the pathologic changes brought about by other immunity mechanisms such as “cell-bound” or “delayed” hypersensitivity. Nevertheless, the auto-immune concept has had important repercussions in the diagnosis and treatment of thyroid disease. Auto-immune thyroiditis can readily be differentiated from other forms of thyroid disease on the basis of a combination of clinical and laboratory findings including serologic, biochemical and radioiodine tests. The precipitin test is the most reliable laboratory test, but the occasional occurrence of a positive test in thyroid neoplasm makes it necessary to carry out thyroid biopsy when the clinical findings are equivocal. The Hyland Laboratories T-A test provides a rapid screening procedure for auto-immune thyroiditis, but false positives may occur in patients with rheumatoid arthritis. On the other hand, the tanned red cell hemagglutination and complement fixation tests are too sensitive for routine diagnostic purposes. Increases in gamma globulin, abnormal flocculation tests, and an accelerated erythrocyte sedimentation rate are of diagnostic value in auto-immune thyroiditis and the results of routine radioiodine tests may be helpful, although occasionally misleading in the euthyroid patient who manifests symptoms of thyrotoxicosis. In the difficult case additional radioiodine tests, such as the perchlorate discharge, thyroxin or triiodothyronine suppression, and thyrotropin stimulation, or stable iodine studies may be necessary to establish the diagnosis without recourse to thyroid biopsy. The treatment of choice in auto-immune thyroiditis is thyroxin in a daily dose of between 0.2 and 0.3 mg. by mouth. This results in a variable but significant shrinkage of the goiter and a return toward normal of the biochemical abnormalities. Thyroxin should be prescribed to all patients irrespective of their clinical status and should be continued indefinitely. In rare instances surgical intervention will be necessary to relieve pressure symptoms or when a thyroid neoplasm is suspected. There is now good evidence that hypothyroidism without goiter, i.e., “primary” hypothyroidism, and auto-immune thyroiditis are variants of the same pathologic process, and that the chronic thyroiditis present in the thyrotoxic gland is a focal lesion of the same type. Patients with thyrotoxicosis who have positive precipitin tests have severe and extensive thyroiditis present in the gland and should be treated with long-term antithyroid drug therapy. Thyrotoxic patients with positive tanned red cell and complement-fixation tests are also best treated with antithyroid drugs, unless there is a definite indication for surgery or radioiodine therapy.

Stimulation of acquired resistance to Schistosoma mansoni in monkeys: Role of eggs and worms

1. 1. Two rhesus monkeys ( Macaca mulatta) were given 10 injections of viable Schistosoma mansoni eggs during a 20–21 week period. The injections were given either subcutaneously or intravenously, and the injected eggs totalled 381,000 for one monkey and 351,000 for the other. As a result of the injections, the two monkeys gave positive “Cercarienhüllenreaktions” (CHR) of high titers, positive circumoval precipitin tests (COP), and they developed other antibodies against eggs and cercariae demonstrated by the Ouchterlony technique. There was however, no indication in either monkey of resistance to a challenge with 1,000 S. mansoni cercariae. 2. 2. One rhesus monkey was given eight intravenous injections of an alum-precipitated aqueous extract of crushed freeze-dried S. mansoni eggs. The injections, which contained extracts from 235,000 eggs, were given every 2nd or 3rd day. As a result of the injections the monkey gave a positive CHR of high titer, a positive COP, and developed other antibodies against eggs and cercariae demonstrated by the Ouchterlony technique. The monkey however, showed no sign of resistance to challenge with 1,000 S. mansoni cercariae. 3. 3. Four rhesus monkeys were each exposed to 2,000–2,500 S. mansoni cercariae of one sex; three monkeys were exposed to female cercariae, and one monkey to male cercariae. No changes occurred in the serum proteins of the monkeys up to 12 weeks after infection. All the monkeys produced positive CHR of relatively low titers, and two monkeys produced weakly positive COP. When these monkeys were challenged with a bisexual infection of 1,000 cercariae 23 weeks after the unisexual infection, a partial but significant resistance against the parasite had developed. 4. 4. It is concluded from these results that the presence of living S. mansoni worms, even though sexually immature, can stimulate acquired resistance to the parasite, and that the presence of eggs is not essential for the development of this resistance. Furthermore, monkeys can develop resistance even though there has been no increase in gamma globulin, and antibodies against egg and cercariae demonstrated by CHR and COP do not by themselves provide protection .

A comparison of tests for thyroglobulin antibody.

A comparison is made of tests for thyroglobulin antibody, using gel diffusion, electroprecipitin, bentonite flocculation, tanned red cell agglutination, and latex slide agglutination techniques on sera from cases of Hashimoto's disease and other thyroid disorders. Any increase in gamma globulin was also noted from the serum electrophoretic pattern. The gel diffusion and electroprecipitin tests are shown to be comparable in their sensitivity, as are the bentonite flocculation and tanned red cell agglutination tests. The flocculation and agglutination tests were oversensitive. The latex slide test in conjunction with the electro-precipitin test is recommended for routine use in the detection of Hashimoto's disease.

Immunoelectrophoresis of Serum in "Lupoid" Hepatitis.

SummaryImmuno- and paper strip electrophoresis of serum proteins were performed on 6 patients with “lupoid” hepatitis and compared with the findings in 13 patients with Laennec's cirrhosis. The following changes were observed in “lupoid” hepatitis: There was a decrease in albumin, alphas haptoglobin, alpha2-beta1 lipoproteins and beta1 A globulin and an elevation in alpha2 M, beta2 A, beta2 M and gamma globulins. Immunoelectrophoresis in Laennec's cirrhosis revealed only an increase in beta2 A, beta2 M and gamma globulins. Paper strip electrophoresis revealed in both diseases a decrease in the albumin fraction and an increase in gamma globulins. The significance of these alterations in the serum proteins is discussed. The beta1 A globulin has been identified with one of the components of the complement and is diminished both in SLE and in “lupoid” hepatitis. This suggests that a similar immunologic process is operating in both diseases.

Serum antibody and protein studies following adrenalectomy in rabbits.

SummaryIncreased circulating levels of antibody following a single intravenous injection of bovine serum albumin were demonstrated in adrenalectomized rabbits, as compared with normal intact controls. Additionally, there was a delay in appearance of maximum titers of antibody in the test group of animals. In animals previously immunized with bovine serum albumin, adrenalectomy produced increased gamma globulin concentrations but failed to recall specific anti-BSA antibody into circulation.

Electrophoretic Serum Studies Studies of Children with Frequently Recurring Acute Tonsillitis

Bruton, 1 in 1952, in his paper on agammaglobulinemia first called attention to the fact that an abnormality in plasma proteins may be responsible for recurrent bacterial infections in a person. Since then, many authors 2 have confirmed that in some cases of increased susceptibility to infections, deficiency of circulating plasma gamma globulin may play a decisive role. It has been established that immune bodies are mainly in the gamma globulin fraction, and gamma globulin formation is connected with resistance to infection. Nevertheless, there is no doubt now that the gamma globulin content, as determined by paper electrophoresis of the serum proteins, is not directly related to resistance to infections of the upper respiratory tract. Payne and Forsyth 3 state that the increase in gamma globulin found in chronic infections is greater than could be accounted for by a rise in specific antibodies, as they form an infinitesimal part of

Hypergammaglobulinemia in mink.

SummaryThe electrophoretic patterns of normal and Aleutian disease affected mink have been determined. The serum from diseased animals had increased total serum proteins, increased gamma globulin, and decreased albumin.

Electrophoretic serum protein studies in chronic human Manson's schistosomiasis.

Summary The serum proteins of 67 patients with chronic schistosomiasis and of 37 controls were studied by paper electrophoresis. Compared to the controls, slight but significant changes consisting of decrease of serum albumin and increase of gamma globulin were found in the infected group. The changes were more pronounced in patients with hepatosplenomegaly than in those without hepatosplenomegaly, but the differences were not significant. No significant relationship was found between the protein abnormalities and the hepatic functional impairment determined by the bromsulfalein retention test. The protein abnormalities had no relation to previous treatment with antimonial agents. The changes were significantly more marked in patients who had an abnormal cephalin flocculation test than in those whose cephalin flocculation test was normal. The gamma globulin was significantly higher in those sera that produced a large amount of precipitate (2+ to 4+) in the circumoval precipitation test than in those that produced either no or a small amount of precipitate (0 to 1+). However, no correlation between the circumoval precipitation test and the cephalin flocculation test was found. These findings indicate that decrease of serum albumin and increase of serum gamma globulin represent a protein response by the human host to chronic infection with Schistosoma mansoni. In view of the known hepatic involvement which occurs in this disease it would seem reasonable to suspect that the protein changes result from this involvement. However, in the present study they could not be correlated at an acceptable level of confidence either with abnormal bromsulfalein retention or with hepatosplenomegaly. The evidence presented supports the view that these changes are due substantially to an immunologic mechanism. This mechanism probably produces a group of antibodies, one of which is the circumoval precipitin.

CHILDHOOD TUBERCULOSIS: CLINICAL VALUE OF THE ELECTROPHORETIC PATTERN OF THE SERUM PROTEINS

The blood serum protein fractions of 138 children with tuberculosis were analyzed by paper electrophoresis serially over a period of many months. Many manifestations of tuberculous infection were studied. The group was divided into 11 categories ranging from healed or arrested tuberculous disease to various stages of activity. The serum protein fractions were evaluated in terms of prognosis, type of tuberculous disease, effect of intercurrent infection and age of patient. It was found that the greatest changes occurred in the gamma-globulin and albumin fractions in reciprocal relation. With the exception of tuberculous meningitis, the increase in gamma-globulin usually corresponded to the severity of disease. Albumin was correspondingly decreased, and was low even in tuberculous meningitis. Both fractions approached normal levels as the patients improved. Relatively normal readings were found in patients with tuberculosis observation or arrested tuberculosis. The greatest deviation from normal was seen in patients with miliary tuberculosis and those with pleurisy with effusion. Here, the gamma and alpha2-globulins were very high and the serum albumin was low. The alpha2 fraction was elevated in the children with more severe disease, including tuberculous meningitis; with clinical improvement it returned to normal more rapidly than the gamma. A rise in the beta-globulin fraction suggests caseation. Confirmatory evidence was obtained in patients with endobronchial disease, tuberculous adenitis and from the only necropsy in the series. The significant changes in the various fractions are further described and discussed.

Alterations of serum proteins in mice acutely and chronically infected with Plasmodium berghei

Mice infected for the first time with Plasmodium berghei showed marked alterations in levels of serum proteins and invariably died with high parasitemias. If such animals were treated with primaquine diphosphate early in the course of infection, however, most of the mice survived as cured animals and serum protein patterns returned to normal. Following reinfection of these cured mice, the latter again became acutely infected as evidenced by parasitemias and dysproteinemias. At the end of the first week of infection, however, an accelerated and exaggerated gamma globulin response was associated with the apparent elimination of parasites from the blood. Subsequently, most mice relapsed with infections characterized by periods of protracted parasitemia. Such relapses were generally non-fatal, showed unpredictable, variable parasitemias, and were essentially unaltered by superinfection attempts. Associated with this chronic state of infection was a generally increased gamma globulin fraction the level of which was variable and which could not be consistently related to individual parasitemias.

Importance of an increased gamma globulin level in the determination of Gm groups in collagen diseases.

Importance of an increased gamma globulin level in the determination of Gm groups in collagen diseases.

Anomalous Panleukocytic Granulation

Abstract Anomalous panleukocytic granulation is described in the peripheral blood, bone marrow and spleen of a 3 year old girl. Myeloid leukocytes showed giant peroxidase and Sudan Black B-positive granules. Lymphocyte corpuscles were positive in the periodic acid-Schiff test. Deviations in the structure and segmentation of the neutrophil nuclei were observed. Increase of gamma globulins and decrease of lipoproteins were found in the blood serum. Hepatosplenomegaly, psychomotor underdevelopment, respiratory tract infections, roentgenologic changes of bones, lungs and heart were also found. The parents were first cousins, and anomalous corpuscles were seen in the father’s lymphocytes. At necropsy diffuse or focal infiltration of the organs by lymphoid, plasma and reticular cells suggested a systemic condition.

Electrophoretic studies on serum proteins of young germfree, conventional and antibiotic treated conventional chickens.

SummaryThe effect of feeding procaine penicillin G (50 mg/kg diet) on the electrophoretic pattern of serum of young conventional chickens was studied and compared with data obtained from germfree animals. While the effect of the antibiotic on morphological characteristics of conventional chicken made itself felt after one month, up to the age of 2 1/2 months no differences were seen in the electrophoretic pattern. Both groups showed an equal increase in gamma globulin over the level found in serum of the germfree animal. At 4 months, however, the antibiotic-treated birds showed lower gamma globulin values than the untreated group, though the level was still substantially higher than found in germfree serum.

CLINICAL OBSERVATIONS ON THE ELECTROCARDIOGRAPHIC CHANGES IN LIVER DISEASES

For the purpose of elucidating the relationship between electrocardiographic changes and clinical and laboratory findings in liver diseases, 83 cases of acute and chronic hepatitis and cirrhosis (25, 20 and 38 cases respectively) including 13 cases which lapsed into hepatic coma were examined and the following results were obtained. 1) Pathological electrocardiographic findings were detected in 73.2 per cent of the whole patients, and the changes in hepatic coma were remarkable without exception. As the most common abnormalities, lowering of T-wave, ST-depression, low voltage and QT-prolongation were observed in 49.6, 29.3, 25.2 and 21.1 per cent respectively, and all these findings were more marked in the clinically severe cases. 2) No appreciable correlation was found between the electrocardiographic changes and the clinical findings such as disorders of nutrition, low blood pressure, cardiovascular murmurs, enlargement of the liver, splenomegaly, anemia and proteinuria. 3) Some parallelisms were noticed between the electrocardiographic changes and the abnormal results of liver function tests such as decrease in cholesterol ester quotient, shift to the right of the serum cobalt reaction, decrease in A/G ratio and increase in gamma globulin. Moreover, lowering of T-wave, ST-depression and low voltage were found more frequently in the group presenting abnormal serum protein patterns. Some discussions were made on the above results in reference to the concept of “hepatogene dysproteinamische Myokardose (Wuhrmann)”.

Effect of adrenocortical hormones on serum proteins of adrenalectomized mice infected with M. tuberculosis.

SummaryFollowing administration of varying amounts of hydrocortisone, desoxycorticosterone, and 2-methyl-9-fluorohydrocortisone to adrenalectomized non-infected mice and adrenalectomized mice experimentally infected with M. tuberculosis, changes in serum proteins were determined by a paper electrophoretic technique. An increase in total protein was observed with hydrocortisone; a decrease in albumin and an increase in alpha3 globulin occurred with hydrocortisone, high doses of desoxycorticosterone, a combination of hydrocortisone and desoxycorticosterone, and 2-methyl-9-fluorohydrocortisone; and an increase in gamma globulin resulted with a high dose of hydrocortisone. The individual effects of the hormones on serum proteins were not apparent in those animals infected with M. tuberculosis. All of the animals, except those treated with 2-methyl-9-fluorohydrocortisone, showed an increase in alpha2 globulin while only the high dose of hydrocortisone produced a decrease in albumin.

Chronic lymphocytic leukemia associated with dysproteinemia and acquired hemolytic anemia

An unusual case of chronic aleukemic lymphocytic leukemia with dysproteinemia and acquired hemolytic anemia is presented. Significant features included: (1) hyperproteinemia with marked increase of gamma globulins, (2) presence of cold agglutinins of the immune type, (3) decreased red cell survival and (4) abnormal bleeding tendency. Electrophoretic analysis of a lymph node extract revealed a high peak in the area of the gamma globulins corresponding to similar elevations in the serum and in the pleural fluid of the patient. These findings indicate a high concentration of gamma globulin in the leukemic tissue of the patient and suggest that not only normal but also leukemic lymphocytes may be the source of gamma globulins.

Tumors and blood proteins

The main laboratory investigations for the diagnosis of malignancy are reviewed. None of them has demonstrated to have a sufficient sensibility and specificness. The results of electrophoretic separation of serum proteins of one hundred and twenty eight patients with malignant diseases and of ten patients with benign forms are reported. From the examination of the results we may conclude: a) Eighty five per cent of the patients with malignant diseases has presented alterations of the electrophoretic pattern while no alteration was evident in subjects with benign forms. b) According to what has been already described by others the most frequent alteration seen in subjects with malignant tumors is the increase of alpha 2 globulins. Wo have seen the highest values of alpha 2 globulins in subjects with gastric and pulmonary cancer and in bone metastasis from prostate and breast cancer. c) Hepatic metastasis from gastric cancer presented increase of beta globulins and alpha 2 globulins. In gastric cancer we have very often seen an increase of alpha 1 globulins too. In four cases of gastric cancer (two infiltrating forms and two old gastric ulcers degenerated) we had no modification of serum proteins. d) We had increase of gamma globulins in pulmonary cancer, bone cancer and in the second stage of linphogranuloma. e) The described alterations of the electrophoretic pattern are common to other pathological conditions, out they assume particular importance in tumors of some organs (stomach, lung, bone). f) The insufficient specificness and sensibility of these modification makes them of no value when other pathological conditions are present in the same patient. g) Electrophoretic pattern is very important in the post-operation course (after removal of tumor) as a token of local relapses or metastasis.

Zone electrophoresis in studies of maternal and fetal sera.

SummaryZone electrophoresis was carried out on 15 pairs of maternal and cord sera. Qualitative differences between all maternal and cord bloods were observed in electro-phoretic patterns stained for proteins and protein-bound polysaccharides. Maternal sera consistently showed decreases in albumin and gamma globulin and increases in alpha and beta globulins. Corresponding cord sera exhibited decreases in alpha and beta globulins and an increase in gamma globulin. Protein-bound polysaccharides associated with alpha and beta globulins were markedly increased in mothers'sera but were decreased below normal in the corresponding cord serum specimens.

The reaction of plasmocyte cell cultures after inoculation of all three types of polio virus

The reaction of the plasmocyte cell cultures from a case of myeloma with decreased gamma globulin synthesis and from a case of myeloma with increased gamma globulin synthesis was tested in relation to all 3 types of polio virus. In both cases the plasmocytoma cells proved to be resistant to the well-known cytopathogenic effect of these viruses in tissue culture. Macrophages in the culture of one case seemed also to be resistant.