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The in vitro effects of ISO on the immune responses of cancer patients were investigated. Forty seven patients with primary tumors (26 lung carcinoma, 14 breast adenocarcinoma, 7 melanoma) were studied. Concanavalin A (ConA)-induced lymphocyte proliferation, natural killer cell (NK) activity, and monocyte chemotaxis were measured. In 40 of the 47 patients (85%), ConA-induced lymphocyte proliferation was depressed; NK activity was depressed in 32 (68%), and monocyte chemotaxis was found to be depressed in 36 (77%). For in vitro studies, an optimum concentration of ISO (100 micrograms/ml per 10(6) cells) was used to treat peripheral blood mononuclear cells. In the presence of ISO, all three parameters were restored to normal or near normal levels in those that were depressed. Under these preincubation conditions in vitro treatment of mononuclear cells from the peripheral blood of normal individuals with ISO had no effect on their activities in the three assays. Similar effects on these three immune parameters were observed when 24 h supernatants obtained from patients' mononuclear cells pretreated with ISO were employed in these assays.

Human T-cell subsets, defined by active E rosette formation, were examined for their ability to produce leucocyte migration inhibitory factor (LIF) in response to mitogen or specific antigen. It was determined that T cells enriched for active rosette-forming (A+) cells produced LIF in response to concanavalin A, whereas T cells depleted of active rosette-forming (A-) cells did not. Similarly, A+ cells from a tuberculin-sensitive donor produced LIF in response to tuberculin purified protein derivative, whereas A- cells from the same donor failed to produce the mediator. Thus, T-cell production of LIF in humans appears to be restricted to those T cells capable of active rosette formation.

A method of two-dimensional electrophoresis has been devised to allow the study of the electrophoretic mobility of urinary lysozyme. Three different phenotypes have been defined in a study of thirteen purified lysozymes obtained from different patients with monocytic leukemia.

Binding of human circulating T cells to established normal and malignant B cell lines results in rosette formation. The percentage of B cells, circulating T cells, and thymocytes able to bind to the B-LCL Raji were 0%, 59 +/- 4% and 61 +/- 6%, respectively. The percentage of rosettes formed between Raji cells and circulating mononuclear cells from 92 normal individuals was 27.8 +/- 5.3%, and remained stable over several months. This phenomenon seems to involve relatively mature B cells, and a T cell marker which appears early in T cell ontogeny. In the peripheral blood, most of the B-LCL binding T cells exhibit a 'helper-inducer' phenotype, as determined with the monoclonal antibodies Leu 3a and OKT4. However, a significant percentage of T cells with so-called 'cytotoxic-suppressor' markers (Leu 2a and OKT8) also bind to B-LCL. The T cells involved in this morphological interactive reaction with B cells might conceivably be specifically involved in regulating B cell functions. Enumeration of this particular subset may be useful in conditions where abnormal T-B cell interactions are suspected.

Mitogenesis and polyclonal immunoglobulin production in peripheral blood lymphocyte cultures activated with Formalin-fixed or autoclaved protein A-containing Staphylococcus aureus were studied. Direct evidence for a dissociation between cell proliferation and polyclonal immunoglobulin production was found, in that S. aureus was not mitogenic after being autoclaved but retained the ability to stimulate B cells to produce immunoglobulin. Trypsin-treated S. aureus lost its binding site for immunoglobulin G, but its mitogenicity was not altered; thus, the protein A binding site for immunoglobulin G on the bacterial cell wall is not required for the stimulation of lymphocyte proliferation. Our data also show a dissociation between cell proliferation and polyclonal immunoglobulin production induced by protein A coupled to Sepharose CL-4B. These results suggest the presence of three distinct active sites on the protein A molecule: one that binds immunoglobulin G molecules, one that stimulates cell proliferation, and one that stimulates polyclonal immunoglobulin production.

Carcinoembryonic antigen (CEA) activity was measured by radioimmunoassay in blood from cystic fibrosis (CF) homozygotes, heterozygote carriers of CF, normal healthy controls, and other patient controls with carcinomas involving gastrointestinal organs. All samples were also screened by electrofocusing for cystic fibrosis protein (CFP), a metabolic marker previously shown to be associated with the CF gene. Significantly increased levels of CEA activity were found in all CFP-positive groups; however, with one exception all patient controls with marked increases in CEA activity were CFP-negative. Immunodiffusion of perchloric acid extracts of CEA-like material from heterozygote carrier blood indicated that the CEA-like material, which was elevated in homozygotes and heterozygotes for CF, showed only partial identity with two separate CEA preparations obtained from colon carcinomas and was not identical to either A, B, or O(H) blood group substances. This glycoprotein material did, however, react with three different anti-CEA antisera. Our finding of an abnormally increased glycoprotein in cystic fibrosis, taken together with previous reports demonstrating abnormalities in the carbohydrate portion of glycoproteins found in various exocrine secretions in CF, further suggests that the primary defect in this disease is manifested partly as a defect in glycoprotein metabolism. This defect may result from an abnormality in one or more of the glycosyltransferases, possibly caused by a more primary defect in polyamine metabolism.

1. Calcium and immunoreactive parathyroid hormone (iPTH) levels were measured in sera of 1334 normal subjects ranging from newborn to over 80 years of age. Albumin was measured in samples from the population of adults, which was 80% white, 15% black and 5% oriental. 2. Serum calcium and iPTH levels in children tended to be higher in the first three years of age; no sex differences were noted. Values for serum calcium and iPTH were higher in children than in adults. 3. Serum calcium, iPTH and albumin showed more variation in groups of white, black and oriental women than in similar groups of men. In white females the mean serum calcium remained fairly constant until age 60, whereas in black women it rose steadily from age 20-29 until age 50-59. Serum iPTH levels were lower in black women than in white women and usually were not measurable in oriental women. 4. In men (white, black and oriental) there was a steady decrease in mean serum calcium with age, and iPTH levels were not different from those observed in white women. 5. Although the number of samples from oriental women was small, the serum calcium was consistently lower and serum albumin was constantly higher than in white or black women, and iPTH levels usually were unmeasurable.

Since seminal components can mediate immunosuppression in vitro, it is possible that some antigen(s) may be common to both the reproductive and immunologic systems. In a group of 70 couples with unexplained infertility, 50 "autoimmune" males and 40 "isoimmune" females had lower than normal percentages of total T cells (mean values +/- standard error of the mean 63 +/- 2% and 60 +/- 2% for immune males and females, respectively, versus 77 +/- 2% and 78 +/- 5% for 50 normal males and females, respectively; P < 0.001). Sheep red blood cell (SRBC) rosetting of lymphocytes was significantly reduced when SRBC were preincubated with sperm extracts (61 +/- 4% versus 9 +/- 2%; P < 0.001) but not when SRBC were incubated with normal serum or when lymphocytes were preincubated with sperm extracts. Antisperm antibody titers in the patients' sera (48 +/- 13) were correlated with their antithymocyte antibody titers (18 +/- 3) (P < 0.01). Moreover, antithymocyte antiserum (titer 1024) cross-reacted with sperm extract (titer 128), and vice versa. This cross-reactivity was significantly reduced by absorption of the sera with sperm cells (P < 0.001), thymocytes (P < 0.001), or white blood cells (P < 0.005). Absorption of autoimmune sperm extracts and seminal plasmas with thymocytes or sperm cells reduced the Coombs' titers, especially immunglobulin G (P < 0.01) and immunoglobulin A (P < 0.025). Similar results were obtained in passive hemagglutiation, immunofluorescence, and cytotoxicity assays. We conclude that sperm and T cells share a common antigen(s).

The P2 protein of bovine nerve root myelin was radiolabeled with 125I in homogeneous solution by the chloramine-T method and purified by gel filtration on Sephadex G-75 to obtain monomeric 125I-P2. Antigen-antibody complexes were isolated by the silica gel, double antibody, or polyethylene glycol techniques by using rabbit antibody to P2. As little as 1 ng/ml P2 could be detected. The RIA was used to measure the P2 content in nerve tissue and isolated myelin. The presence of P2 in spinal cord as well as in the peripheral nervous system was confirmed. Peptides isolated by CNBr digestion of the P2 protein were tested in the RIA. CN-1, comprising 80 to 90 residues from the interior of the molecule displayed complete immunologic cross-reactivity with intact P2. Neither CN-2, representing 18 amino acids from the COOH terminal, nor CN-3, representing 20 amino acids from the NH2 terminal, showed cross-reactivity. Since the major determinant for experimental allergic neuritis in the rabbit is located in peptide CN-2, our present data suggest that the major neuritogen and the major determinant(s) for humoral antibody response in this species may be at different locations within the P2 molecule.

A nontransfused 14-month-old female infant was investigated for persistent neutropenia of eight months' duration, with absolute neutrophil counts ranging from 410 to 935 cu mm. The patient's sera reacted with neutrophils from her own peripheral blood, from normal donors, and from her mother, all these having the neutrophil antigen NA 1, but not with neutrophils from NA 1-negative donors, including the father. The autoantibody was detectable by capillary agglutination and by indirect immunofluorescence techniques but not by complement-dependent cytotoxicity. No antibody was found in the mother's serum. Studies on three occasions showed good correlation between the appearance of circulating autoantibody and the peripheral neutrophil counts. Our observations, together with previously published reports, suggest a possible relationship of NA 1 antigen and the disease susceptibility of NA 1-positive infants to autoimmune neutropenia.

Based on remarkable similarities between the central nervous system and the immune system [e. g., both systems have memory cells, both appear to have identical receptors for dopamine, acetylcholine, enkephalins, endorphins, sharing of antigenic determinants on one or another CNS cell and one or another type of immunocyte cell, both systems communicate by soluble substances (e.g., neurotransmitters and lymphokines, respectively)], we have postulated that some forms of Alzheimer's disease are due not to CNS cell death but rather to excess suppression of the brain "B-cell equivalent". We found a pyrrolidone analog useful in stimulating lymphocyte B-cell mitogenesis and function in vitro; this agent subsequently proved dramatically effective in several patients with severe T cell dysfunction and severe recurrent viral infection due to excess T cell suppression. Its use (3-6 months) proved remarkedly effective in certain patients with Alzheimer's disease (frontal lobe cerebral atrophy on CAT scan, duration at least 2 years). A subset with certain immunological dysfunction responded dramatically both immunologically and clinically. In responders in in vitro studies, the defect was corrected in vitro in the presence of the pyrrolidone analog but not by various neuroleptics. Patients without the defect or with the defect but no in vitro correction by pyrrolidone analog agent did not respond clinically. A switch from pyrrolidone to placebo resulted in immunologic and clinical relapse in 2-4 months.

Eighteen patients affected by itching, urticaria, eczema, angioedema, and asthma related to food-stuff intake were studied and classified in two groups (true food allergy and pseudoallergy) on the basis of clinical data, skin prick tests, total and specific IgE levels (PRIST and RAST) and double-blind challenge test. Autologous mixed lymphocyte reaction (AMLR) and T cell activation markers were thought to be tests possibly useful to discriminate between 'true' food allergy and 'pseudoallergy'. The present study failed to show either a significant increase in T cell activation markers (MLR4, Ia) or a significant decrease in AMLR proliferation in such subjects as compared to normal controls. In addition, we found no differences between 'true' allergic and 'pseudoallergic' patients on the basis of the parameters evaluated. Although the AMLR defect was reported both in asthma and in dermatitis, and therefore was thought to be related to atopy, the present data do not confirm this hypothesis in 'true' food allergy.

Since purine nucleoside phosphorylase has been associated with suppressor function in lymphocytes, enzyme activities were studied in autologous rosette-forming cells, a subset showing suppressor properties. Levels of this enzyme were higher in these cells than in other T cells. Con A induction of autologous red cell receptors and suppressor activity of T cells were both inhibited in dose-dependent fashion by Formycin B, a well known inhibitor of purine nucleoside phosphorylase. Inhibition of autologous rosette-forming cells was obtained after pulse treatment of cells with Formycin B for as little as 1 hr, whereas cell proliferation was only inhibited when Formycin B was present throughout culture; this confirms the independence of cell proliferation, and development of red cell receptors and suppressor activity. This study indicates a crucial role for purine nucleoside phosphorylase enzyme in induction of T cell suppressor activity.

The mechanism by which heparin inhibits the alternative complement pathway (ACP) by a fluid-phase activator, CoVF, has been studied. Results presented here indicate that heparin's major (rate-limiting) effect on the fluid-phase activation of the ACP was to potentiate Factor H activity. Such an effect results in a very efficient inhibition of C3b and C3bBb function and restriction of subsequent complement activation and hemolytic activity. Evidence was obtained to indicate that soluble heparin H shifted anodally. Assuming that the rate-limiting inhibitory effect of heparin is to potentiate Factor H, then C3-converting complexes such as CoVF-Bb, which do not require C3b for activity, should not be effected by heparin. Indeed, the inhibitory effect of heparin on C3 conversion in EGTA-Mg2+ serum-CoVF mixtures was lost with a prolonged incubation time (i.e. 60-90 min at 37 C). This finding indicated that with time ACP-mediated cleavage of C3 was able to bypass the heparin-mediated inhibitory step. From these studies it is suggested that heparin restricts the C3-converting activity due to soluble C3bBb complexes but not the C3 conversion due to CoVF-Bb complexes. Heparin-mediated restriction of the ACP activation by CoVF was used to calculate the relative percentages of C3 conversion due to C3bBb or CoVF-Bb complexes. In carefully controlled experiments, heparin could not prevent the spontaneous conversion of C3 which occurs upon removing functional Factor H from the sera. Addition of isolated Factor H restored heparin's inhibitory effect on the ACP. Kinetic studies of heparin's inhibition of ACP-mediated lysis of rabbit erythrocytes indicated that heparin's inhibitor functions did not occur until after the addition of an ACP activator. Each of these findings is consistent with the postulate that the major (rate-limiting) effect of heparin on the ACP is to potentiate the function of Factor H on activated C3b.

Fourteen infants with autoimmune neutropenia reported in the literature have been reviewed. Autoantibodies directed against their own neutrophils were demonstrated in the sera of these infants by agglutination, complement-dependent cytotoxicity, and immunofluorescence techniques. These antibodies were highly specific and were directed against antigens present on neutrophils. Among the currently known neutrophil antigens (NA1, NA2, NB1, NC1, NE1, ND1, 9A), antibodies reacting with either NA1 or NA2 have been identified frequently in the sera of infants with autoimmune neutropenia. Good correlation was demonstrated between the presence or absence of autoantibodies and the episodes of neutropenia in many cases. Antibodies from the patients also reacted with neutrophils from their parents and from normal unrelated volunteers when they shared the neutrophil-specific antigen against which the antibody was directed. Antibodies demonstrable by complement-dependent cytotoxicity appeared to detect different antigens which may also cause autoimmune neutropenia. Infants with this disorder were healthy at birth and for a few months afterwards, then became chronically ill with such symptoms as intermittent fever, diarrhea, and infections. Their hemoglobin levels, lymphocyte and platelet counts, and other immunological studies were normal except for severe to moderate neutropenia.

Immunologic studies were performed in 21 patients with multiple sclerosis (MS) and 16 with the Guillain-Barré syndrome (GBS). Levels of thymus-derived (T) cells measured by "total" and "active" rosette formation between sheep erythrocytes and peripheral blood mononuclear cells (TEt, TEa) were within normal limits in all the patients, with the exception of four GBS patients, including one who also had received chemotherapy for lymphoma and three who were receiving steroids. When lymphocytes from the 21 patients were incubated with the bone-marrow-derived (B) lymphoblastoid cell line PGLC-33H, there were, for 12 of 18 MS patients and 11 of 16 GBS patients, significant decreases in a subpopulation of peripheral blood T lymphocytes that form "PGLC rosettes" (PGR) with the PGLC-33H cells. (Peripheral blood T cells from normal individuals formed PGR with 23.9 +/- 3.8 percent of PGLC-33H cells.) Using the 125l-C1q binding assay, immune complexes were detected in the serum of 14 of 19 MS patients and 15 of 16 GBS patients. An association between increased C1q binding and decreased PGR values was found in 10 of 18 MS patients and 12 of 17 GBS patients. The results suggest that in both diseases the etiology may involve a decrease in the subset of T cells that bind to the IgM-producing cell line PGLC-33H, in association with the appearance of circulating immune complexes containing the infectious viral agent.

Serum samples were collected from 113 healthy Caucasian volunteers before and after vaccination with meningococcal polysaccharides (MPS) group A and group C. Antibodies to MPS group A and group C were measured and sera were typed for several Gm and Km(1) allotypes. A significant association was found between the Gm 1,3,17; 5,13,14,21 phenotype and low immune responsiveness to MPS group A. These results suggest the possible existence of an immunoglobulin allotype-linked immune suppression (Is) gene(s) in man.

A study of Gm allotypes in a Caucasoid family with hypogammaglobulinaemic probands, showed qualitative (unexpected or lacking Gm allotypes) and quantitative (increased or decreased Gm contents) abnormalities in many relatives. Part of these observations can be most probably accounted for by inheritance of a GM1,17; 5,28 haplotype, not described in Caucasians yet, and by an in vivo expression of latent Gm genes.

The distribution of Glm(f, z, a, and x), G3m(b0, b1, b3, b5, c3, c5, g, s, t and v), A2m(1 and 2) and Km(1) (formerly Inv(1)) allotypic determinants has been examined in specimens from the inhabitants of two transplanted Tlaxcaltecan villages (Cuanalan and Saltillo). The results indicate that Gmza;g Am1, Gmza;g Am2, Gmzax;g Am1, Gmza;bst Am1, Gmza;bst Am2, Gmf;b Am1, Gmza,b Am1, Gmza;b Am2 and Km1 are polymorphic or marginally polymorphic in both populations, while Gmza;bc3,5 Am2, Gmza;bs Am2, and Gmzax;g Am2 were detected only in Saltillo. Two related individuals from Saltillo have either a Gmf;g Am1 or Gmf;-Am1 haplotype while a third unrelated individual had either a Gmf;g Am1 or Gm-;g Am1 haplotype. The frequencies observed for "residents" of Cuanalan are similar to those for other Indian populations in Mexico. Estimation of Caucasian and African admixture within the two communities indicates significant heterogeneity among the inhabitants of Cuanalan, in that Tlaxcaltecan residents have no detectable African admixture and significantly less Caucasian admixture than recent immigrants, with Tlaxcaltecan-immigrant hybrids intermediate, while no significant variation was observed among the subdivisions of Saltillo. However, Saltillo has greater Caucasian and African admixture than Cuanalan. Admixture estimates based on Gm haplotypes appear to agree much better with known historical events than those generated by blood groups, indicating that Gm is a better estimator of admixture than blood groups under certain circumstances.

The evidence that demonstrates a structural and functional interrelationship between the immune system and central nervous system is reviewed. Based on striking analogies between these two systems, the proposal was made that at least some neuropsychiatric diseases can be evaluated by functional studies of peripheral blood immunocytes. This hypothesis was supported by the results of immunologic function studies of various subpopulations of immunocytes obtained from patients with Alzheimer's disease and retinitis pigmentosa.

B-cell 'activation' in cultures stimulated with pokeweed mitogen (PWM), Staphylococcus aureus strain Cowan I, or formaldehyde-fixed Salmonella paratyphi B (SPB) was evaluated by enumeration of cells secreting immunoglobulin (Ig) and by quantitation of Ig released into culture supernatants. A dissociation between these two values was found after day 6 in cultures activated with PWM or SPB, suggesting that Ig-secreting cells (ISC) are heterogeneous in terms of Ig secretion rate. Generation of ISC in cultures activated with PWM or SPB was partially inhibited by hydroxyurea, but Ig levels in culture supernatants were not affected. These results indicate that there are at least two subpopulations of ISC in stimulated peripheral blood lymphocyte cultures, one sensitive to, and the other resistant to, hydroxyurea. The hydroxyurea-resistant subpopulation appeared to be more mature and to release most all of the Ig detected in culture supernatants. Furthermore, time-course studies of ISC numbers and Ig levels showed that each ISC in SPB-stimulated cultures (but not in PWM-stimulated cultures) was more active in Ig synthesis and secretion after day 8 than before day 6, indicating that after day 8 most of the ISC in cultures activated with SPB were hydroxyurea-resistant. These studies suggest that SPB is another useful polyclonal B-cell 'activator' for studies of human B-cell differentiation and function, and that SPB defines two distinct subsets of B cells.

We have developed a nephelometric technique for determining titers of rheumatoid factor. Serum dilutions are added to a mixture of commercially available latex particles of small size (0.098 micrometer) and human gamma-globulin. Rheumatoid sera induce a substantial increase in the light scattering properties of the mixture, and the highest dilution significantly increasing the light scattering is considered as the titer for that serum. This technique is simple to use, provides objective results, and can be automated for analysis of large numbers of samples.

This study was designed to answer the question, do molecules with carcinoembryonic antigen (CEA) activity from colon, breast, and ovarian cancer differ? Extracts of two breast and three ovarian cancers with CEA activity were compared to three colon cancer CEA preparations and to the related antigen, colon carcinoma antigen-III, in terms of lectin- and antiserum-binding properties. With the use of Farr-type radioimmunoassays with the lectins, concanavalin A and wheat germ agglutinin, the iodinated colon CEA and CEA-like preparations from breast and ovarian cancer all showed distinctly different patterns of binding. Specificity of binding was confirmed by inhibition studies with the relevant monosaccharides. Similarly, with antisera prepared against colon CEA, colon carcinoma antigen-III, or breast CEA, it was shown that, although all preparations shared some antigens, unique antigenic determinants were also present on all preparations. These data are consistent with the concept of a series of closely related CEA and CEA-like molecules with distinct characteristics for each tissue source of CEA.

Serum samples were collected from 30 healthy adult Caucasian volunteers before and after immunization with native type III polysaccharide of group B streptococcus. Serum antibody to this polysaccharide was measured and sera were typed for several Gm and Km(1) allotypes. A significant interactive effect of Gm(23) and Km(1) was found on immune responsiveness to native type III group B streptococcus polysaccharide antigen.

Antibody titres to whole ovary, theca cells, granulosa cells and endometrium were determined by passive haemagglutination and immunofluorescence assays in sera and in cervical and vaginal secretions from 13 patients with endometriosis. Antibody titres to endometrium (mean log2 +/- s.e.m., 7.08 +/- 0.80; P less than 0.0001), ovary (3.58 +/- 0.87; P = 0.0092), theca cells (4.42 +/- 0.73; P less than 0.0001) and granulosa cells (3.33 +/- 0.63; P = 0.0024) were significantly higher in the patients' sera than in sera from 15 normal non-pregnant females. Antibody titres to granulosa cells were elevated (7.97 +/- 1.46; P = 0.0424) in their cervical secretions. Antibody titres to all tissues tested were similar in vaginal secretions of patients and controls. Immunofluorescent antibody assay of biopsied endometrial tissue and sera from the patients revealed the antibodies to be primarily IgG and IgA. The results suggest that autoantibodies to endometrium and ovary are present in patients with endometriosis.

Previous studies have shown that DLEs with TFd activity produce both Ag-dependent specific effects (mediated by TFd) and Ag-independent effects on CMl as demonstrated in vitro by agarose LMl. In the present study, Sephadex G-25 gel filtration provided a simple method for separating the DLE components responsible for each effect into distinct fractions. Ag-independent LMl was produced predominantly by Sephadex fraction l, of MW greater than 5000. The active components, further purified on Bio-Gel P-10, were shown to be of MW 14,000 to 17,000 and to contain both polypeptide and ribonucliotide material. The Ag-independent LMl activity was stable to heating at 56 degrees C for 30 min but was partially destroyed at 80 degrees C for 30 min, and the responsible components were shown to act on PMN directly. Ag-independent ELM was produced exclusively by material in Sephadex G-25 fraction V and also acted directly on PMN, whereas the Ag-dependent specific LMl activity was found predominantly in fraction lVb and to a lesser extent in fraction V and could not be detected in a direct assay using only PMN. In addition, a new activity, designated "Ag-dependent ELM activity," which caused increased migration in the presence of Ag, was found in Sephadex fraction lVa. This latter activity might mask the Ag-dependent LMl activity in fraciton lVb. Bio-Gel P-2 chromatography separated the components producing Ag-dependent and Ag-independent effects in fraction V into two separate subfractions (Va and Vb) of MW 1100 to 2000 and less than 900. The activity in fraction lVb eluted at a position identical to that of the components in fraction Va on Bio-Gel P-2. Fractions Va and Vb contained both polypeptide and ribonucleotide material. The Ag-dependent specific LMl or TFd activity was found to be partially inactivated at 56 degrees C and completely destroyed at 80 degrees C. The components responsible for this TFd activity were further purified by HPLC on ODS resin. The TFd activity was mediated by components with retention times much greater than that of adenosine 3'-monophosphate. The active fraction was composed of both polypeptide and ribonucleotide material but did not contain deoxyribonucleotides.

Autoantibody determinations in 1284 healthy Caucasian subjects of various age groups were made by indirect immunofluorescence for anti-nuclear, anti-gastric, and anti-thyroglobulin antibodies. A sex-dependent relationship between age and prevalence of anti-gastric and anti-thyroglobulin antibodies was found. No association was found between age and anti-nuclear antibodies.

Serum samples from 40 Danish patients with familial polyposis coli and 105 normal blood donors were typed for eight Gm and one Km markers. The distribution of all Gm phenotypes as a group was significantly different in the patient population as compared to the controls. Examination of individual Gm phenotypes showed an increased frequency of Gm3;5,13 in the patients.

The action of an anti-alpha 1-AGP antibody on AMLR, anti-T3 and PHA T-lymphocyte proliferative response was evaluated. We observed a strong dose-dependent inhibition on T-lymphocyte proliferative responsiveness to autologous non-T cells and to anti-T3 stimulus, whereas PHA activation was unaffected. A lower degree of inhibition of the proliferative response was also observed on pretreating both T and non-T cells with the antibody; the addition of anti-alpha 1-AGP in the culture containing cells pretreated with the antibody showed a further inhibition of thymidine incorporation. The data suggest a direct influence of the antibody on membrane alpha 1-AGP and support a positive role of this glycoprotein (distinct from Ia and T3 antigens) on both anti-T3 and autologous non-T cell T-lymphocyte responsiveness, thus indicating the involvement of alpha 1-AGP in the T3-Ti antigen-specific pathway of T-cell activation.

Sera from cystic fibrosis (CF) homozygotes and obligate heterozygotes contain a CF factor (gamma CF factor) not found by isoelectric focusing in thin-layer polyacrylamide gels in most normal control sera. In addition, sera from most obligate heterozygotes lack another protein (bland B, C, or D) that is commonly found in sera from most normal and cystic fibrosis individuals. A standardized, biophysical assay is described that employs isoelectric focusing for the detection of both CF homozygotes and heterozygotes based on the analysis of whole serum for the presence of the gamma CF factor and bands B, C, and D. Results of analyzing sera from selected CF patients by isoelectric focusing indicated that there is a general correlation between the amount of the gamma CF factor and the clinical severity of the disease. Partial purification and characterization of the gamma CF factor and protein bands B, C, and D was accomplished by using DEAE-cellulose chromatography, Sephadex G-200 gel filtration, sequential molecular filtration through a series of Amicon Diaflo ultrafiltration membranes, affinity chromatography, and cellulose acetate electrophoresis. The gamma CF factor is a cationic protein with a pI of 8.46+/-0.05, has gamma electrophoretic mobility, a molecular weight between 3,500 and 10,000, and apparently exists in CF serum in 2 forms (free in solution and complexed to IgG). Bands B, C, and D are cationic proteins with pI values of 7.85 to 8.10, have gamma electrophoretic mobility and a molecular weight of approximately 100,000-150,000.