William D. Terry

Amyloid Fibril Proteins: Proof of Homology with Immunoglobulin Light Chains by Sequence Analyses

The sequences of the 35 and 36 amino-terminal amino acids of two purified amyloid fibril proteins have been determined. Results indicate that these two proteins are derived from homogeneous immunoglobulin light chains of variable region subgroup VκI. The relation between amyloidosis and immunoglobulins is thus more firmly established.

Metabolic properties of IgG subclasses in man

Metabolic properties of the four subclasses of human IgG were investigated by performing 47 turnover studies in individuals with normal IgG serum concentrations, as well as in patients with an increased level of one of the subclasses. Studies in 12 subjects with normal IgG serum concentration showed that the average biologic half-life of G(1), G(2), and G(4) was 21 days, while that of G(3) was only 7.1 days. Fractional catabolic rates of G(1), G(2), and G(4) were 6.9 to 8% of the intravascular pool per day. G(3), however, had a higher fractional catabolic rate, amounting to 16.8% of the intravascular pool per day. Distribution of the subclasses was such that the intravascular compartment contained 51-54% of the total body pools of G(1), G(2), and G(4), but 64% of the total body pool of G(3).The short survival and high fractional catabolic rate of G(3) is an inherent property of these molecules, and is not due to denaturation during isolation and radiolabeling. This was demonstrated by studies of a patient with a serum G(3)-myeloma protein. The survival of her own protein, separately labeled either in vivo with guanidoarginine-(14)C or in vitro with (125)I, was determined in the patient. Survivals of the in vivo and in vitro labeled proteins were identical.G(1) and G(3) serum concentrations and synthetic rates were determined. The mean serum concentration of G(1) was 6.8 mg/ml and that of G(3) was 0.7 mg/ml, while their synthetic rates were 25.4 and 3.4 mg/kg per day respectively. The low serum concentration of IgG(2) thus results from a combination of high catabolic and low synthetic rates. Studies in 10 patients with multiple myeloma showed that an elevated serum concentration of any IgG subclass was associated with shortened biologic half-life and increased fractional catabolic rate of all subclasses. The implications of this concentration-catabolism relationship are discussed. The serum concentration of nonmyeloma IgG was usually low in myeloma patients and the synthesis of nonmyeloma IgG was somewhat decreased, suggesting that low serum concentrations of nonmyeloma IgG result from decreased synthesis, as well as from an increased fractional catabolic rate.

SUBCLASSES OF HUMAN GAMMA-2-GLOBULIN BASED ON DIFFERENCES IN THE HEAVY POLYPEPTIDE CHAINS.

Three subclasses of human γ2-globulin (IgG) molecules were detected in normal human serum with antiserums prepared in monkeys. These subclasses, designated γ2a-, γ2b-, and γ2c-globulins, have antibody activity. The distinguishing antigenic characteristics of each subclass were associated with the heavy polypeptide chains and the F (fast) fragments resulting from treatment of γ2-globulins with papain.

Passive immunotherapy of cancer in animals and man.

Publisher Summary Immunologic manipulations to control tumor growth can essentially be divided into passive and active categories. Passive immunotherapy refers to approaches in which immunologic reagents, such as serum, cells, or cell products that are thought to have antitumor activity, are administered to a tumor-bearing host. This chapter reviews recent studies of the use of passive immunotherapy for the treatment of cancer in animals and man. Immune depression in cancer patients has been well documented and attempts to actively stimulate both nonspecific and specific antitumor immune reactions in cancer patients is generally let down by intrinsic defects in the ability of the host to respond. The passive administration of immune reagents can be capable of reacting against the tumor independent of the hosts immune competence. Therefore, passive therapy is regarded as an attractive area of investigation in tumor immunotherapy. The chapter summarizes the existing information concerning the use of subcellular products, such as immune RNA or transfer factor, in the treatment of animal and human malignancy. It is noted that because of immunodepression caused by cancer treatments, passive immunotherapy is considered independent of host immune competence, and is therefore an ideal candidate for inclusion in combined-modality approaches to cancer therapy.

Red cell membrane glycoprotein: Amino acid sequence of an intramembranous region

Abstract Human erythrocyte glycophorin has been purified and partially sequenced. The portion of the sequence reported here (51 residues) represents a unique region of glycophorin that, on the basis of labeling experiments reported elsewhere, is probably associated with the hydrophobic interior of the red cell membrane. This sequence has the anticipated hydrophobic characteristics for interaction with the hydrocarbon interior of a membrane and, as far as we are aware, represents the first reported sequence from a hydrophobic region of an integral membrane protein. There is a distribution of charged and hydrophobic residues topographically similar to a cross-section of a phospholipid bilayer, a structure many now accept as the basic feature of a biological membrane. We propose that the hydrophobic sequence of approximately 23 residues comprises the intramembranous domain of human erythrocyte glycophorin and is intimately and possibly specifically associated with lipids of the membrane.

alpha foetoprotein and serum albumin show sequence homology.

α FOETOPROTEIN (AFP) is a major plasma protein of the foetus1, where it is produced by the yolk sac and the liver2. In adults its concentration is extremely low3 except in patients with tumours such as hepatomas and teratomas4,5. AFP has a molecular weight of 70,000, consists of a single polypeptide chain and contains about 4% carbohydrate6. The similarity of the chemical properties of AFP and albumin and the fact that their concentrations in the serum are high and inversely related7 has led to the suggestion8 that AFP may be a foetal counterpart of albumin. We have determined amino acid sequences of fragments of human AFP and found homology between these and the albumin sequence.

Immunoglobulin E in Immunologic Deficiency Diseases. I. RELATION OF IGE AND IGA TO RESPIRATORY TRACT DISEASE IN ISOLATED IGE DEFICIENCY, IGA DEFICIENCY, AND ATAXIA TELANGIECTASIA

Serum immunoglobulin E concentration was studied in normal children and adults, in 25 patients with isolated IgA deficiency, and in 44 patients with ataxia telangiectasia using a double antibody radioimmunoassay. The geometric mean IgE level of the normal adult population studied was 105 ng/ml, with a broad 95% interval (5-2045 ng/ml). Individuals with concentrations less than 15 ng/ml were considered to be IgE deficient. IgE deficiency, defined in this way, was observed in 7 of 73 normal adults and was not found to be associated with respiratory tract disease.80% (35 of 44) of patients with ataxia telangiectasia (AT) were IgE deficient, 66% were IgA deficient, and 57% had combined IgE and IgA deficiencies. Although 45% of the patients with AT had respiratory tract disease, there was no correlation found between IgE deficiency or combined IgE and IgA deficiency and respiratory tract disease in these patients.11 of 25 individuals with isolated IgA deficiency were also IgE deficient. All 11 patients with both IgA and IgE deficiency were uniformly asymptomatic. However, there was an extremely high incidence (71%) of respiratory tract disease in IgA-deficient individuals who were not IgE deficient. These data fail to support the concept of a protective role for IgE in respiratory tract immunity. The possible role of IgE in the pathogenesis of respiratory tract disease in IgA-deficient patients is discussed.

Structural Identity of Bence Jones and Amyloid Fibril Proteins in a Patient with Plasma Cell Dyscrasia and Amyloidosis

The partial amino acid sequence of the amyloid fibril protein isolated from the small intestine of a patient with plasma cell dyscrasia and associated amyloidosis has been determined and compared with the sequence of the kappa-type Bence Jones protein isolated from the urine of the same patient. Identical sequences were observed for the 27 amino-terminal residues that could be compared. The C-terminal tryptic peptide of the amyloid protein was identical with that of the Bence Jones protein. Apparent molecular weights and amino acid compositions of the Bence Jones and amyloid proteins were similar. It appears, therefore, that the predominant protein present in the amyloid deposits in this patient was an intact kappa-type light polypeptide chain that was identical with the urinary Bence Jones protein.

Gamma G4-Globulin Antibody causing Inhibition of Clotting Factor VIII

HAEMOPHILIA results from the absence of clotting factor VIII. The presence of a circulating inhibitor to factor VIII causes a disease which resembles haemophilia. Five patients with inhibitors shown to be γG-antibodies have been reported1–3.

Immunotherapy of malignant melanoma.

Publication of the results of a trial in which levamisole, a chemical that stimulates some components of the human immune system, had no effect on the clinical course of malignant melanoma (see the...