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Salmonella paratyphi B (S. paratyphi B) has been previously characterized as a human T-independent polyclonal B cell activator. To define further the nature of the bacterial structure responsible for these properties, we studied the effects of autoclaving and enzyme treatment of S. paratyphi B on its stimulatory capacity. We found that both autoclaving and papain treatment decreased the ability oF S. paratyphi B to induce B cell activation, while trypsin treatment did not affect this capacity. Neither type of treatment affected the binding of S. paratyphi B to lymphocytes, suggesting that binding and B cell stimulation are mediated by different structures. The observation that B cell stimulation was significantly reduced by papain treatment led us to attempt to purify membrane proteins so that we could investigate whether they shared the stimulating capacity of S. paratyphi B, A water-insoluble, 43–45,000 mol. wt. protein, rich in aspartic acid, glutamine, glycine, alanine and leucine, similar in mol. wt. and physicochemical properties to the porins of other gram negative bacteria, was isolated and designated as outer membrane protein (OMP). This protein was equally efficient to S. paratyphi B in inducing T-independent B cell activation. By performing time-course studies of [3H]-thymidine incorporation we observed a burst of mitogenic activity after stimulation of PBL or purified B cells with both S. paratyphi B and OMP peaking at 48–96 hr of culture (compared to 96–120 hr for the PWM proliferation peak), and with a magnitude of roughly 10% of that observed after PWM stimulation. Given the fact that the proportion of B lymphocytes in PBL is 4–12%, it appears likely that the proliferation burst seen with S. paratyphi B and OMP corresponds to a mitogenic effect mainly restricted to the B cell population. [ABSTRACT FROM AUTHOR]

Endometriosis occurs in 4-17% of females of reproductive age and is often associated with primary and secondary infertility (Lachlan. 1972; Ranney, 1980). However, the factors governing its aetiology are not clear. Genetic, hormonal, enzymatic and immunological phenomena have been postulated (Weed & Arguembourg., 1980). Complement component C3 is found lining the epithelial cells of endometrial glands in patients with endometriosis. indicating possible formation of immune complexes (Weed & Arguembourg. 1980) A reduction in the number of T lymphocytes and an increase in the amount of immunogiobulin in endometrial tissue have been reported in 56 patients with endometriosis (Startseva, 1980). The presence of autoantibodies to endometrium in these patients, however, has not been established. Moreover, endometriosis is sometimes associated with anovulation (Soules (et al., 1976) and inadequate corpus luteum function (Grant. 1966; Hargrove & Abraham, 1980). Since patients with anovulation and ovarian disorders may have ovarian antibodies in their circulation (Fialkow, 1966; Mathur et al., 1980a,b; Coulam & Ryan, 1979), it is possible that patients with endometriosis may have ovarian and endometrial autoimmunity. Also, since endomelriosis is a disease involving the reproductive tract, a study of cervical and vaginal secretions would seem relevant, [n the present study, sera and secretions from patients with endometriosis were tested for the presence of autoantibodies to ovary and endometrium. [ABSTRACT FROM AUTHOR]

Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000-25,000 which had all the activities of unseparated TS. [ABSTRACT FROM AUTHOR]

The possible influence of sex steroid hormones on circulating IgE levels in general and IgE anti- Candida antibodies in particular was studied by quantification of plasma levels of progesterone, estradiol and IgE (total and anti-Candida-specific) in females during the follicular and luteal phases of the menstrual cycle, and during pregnancy. IgE levels during the follicular and luteal phases were not significantly different, although the mean values for the luteal phase were slightly lower. This trend was apparent in daily samples from two normal females during one menstrual cycle. During pregnancy, when the levels of circulating sex steroids were high, IgE levels were only slightly higher than in the follicular and luteal phases. In men and in gonadal dysgenetics, circulating progesterone levels were similar to those of women during the follicular phase (i.e., lower than in the luteal phase or in pregnancy), but the IgE levels were not different. The apparently low levels of IgE during the luteal phase may therefore be due to physiological factors other than fluctuations in the sex steroid hormones. From the present studies, it is apparent that sex steroid hormones have little or no effect on humoral IgE levels, in marked contrast to previously described correlations for other immunogiobulins, especially anti-Candida antibodies. [ABSTRACT FROM AUTHOR]

Antibodies to native human collagen were detected by passive haemagglutination in the serum of sixteen of thirty-six subjects with selective IgA deficiency (44.4%), compared to 2-5% of control subjects. The sixteen subjects with anti-collagen antibodies included four asymptomatic subjects, five with recurrent infections, four with ataxia telangiectasia, and one each with lymphoma, asthma, and rheumatoid arthritis. There was no statistically significant correlation in individual subjects between the presence of anti-collagen antibodies and antibodies to human IgG, IgA, IgM and ruminant proteins. [ABSTRACT FROM AUTHOR]

The metabolism of radio-iodinated IgG was studied in seven patients with IgG deficiency (<600 mg/100 ml). The group comprised two patients with primary hypogamma-globulinaemia, one with primary hypogamma-globulinaemia and nodular lymphoid hyperplasia, and one each with chronic lymphatic leukaemia (CLL), γG multiple myeloma, renal homotransplantation and the nephrotic syndrome. All patients had markedly reduced plasma and total body pools of normal IgG with normal distribution (intravascular and extravascular pools). An increase in the initial urinary excretion of free isotope in one patient was attributed to a degree of protein denaturation. Compared to the normal range of 20-60 mg/kg/day for IgG synthesis, the patients with primary deficiency and the patient with CLL all had markedly reduced synthesis of normal IgG (2, 5, 4 and 7 mg/kg/day respectively). These patients also had a prolonged or normal plasma T½ and a normal or decreased fractional turnover rate (FTR). The patients with deficiency of normal JgG secondary to multiple myeloma, renal homotransplant or nephrotic syndrome all had an IgG synthesis rate at the lower limit of the normal range with values of 19, 21 and 19 mg/kg/day respectively. They had increased catabolism with a short plasma T½ and increased FTR. An assessment of the factors controlling the metabolism of normal IgG is important in the individual patient as regards the management of their recurrent infections with therapeutic human γ-globulin. [ABSTRACT FROM AUTHOR]

Metabolic turnover studies were performed with radio-iodinated IgG in twelve patients with a serum IgG level greater than 1600 mg/100 ml (six with monoclonal gammopathy and six with a polyclonal increase in IgG associated with liver disease). The six patients with an IgG monoclonal protein comprised four multiple myeloma, one benign monoclonal gammopathy and one biclonal gammopathy presenting as Waldenström's macroglobulinaemia. The six patients with liver disease comprised two patients with cirrhosis, two with infective hepatitis and two with chronic active hepatitis. The injected IgG was either autologous normal IgG (five cases), autologous monoclonal IgG (five cases), homologous normal IgG (one case) or therapeutic intravenous HGG (two cases). The plasma volume was increased in six patients; the plasma IgG pool in nine; and the total body IgG pool in seven. The plasma T½ was normal in one patient with monoclonal and one patient with polyclonal gammopathy but shortened in the other ten studies with mean values of 11.3 and 11.0 days in monoclonal and polyclonal gammopathy respectively. The fractional turnover rate was normal in two studies in polyclonal gammopathy and increased in the other ten with mean values of 13.6% per day in both groups of patients. The IgG synthesis rate was significantly increased in all studies except for a reduced synthesis of normal IgG in one patient with multiple myeloma. The mean synthesis rates in monoclonal and polyclonal gammopathy were respectively 6.7 and 4.1 times the mean synthesis rate in normal controls. The pattern of increased synthesis and increased catabolism in such patients confirms published reports in some diseases and demonstrates a similar pattern in chronic active hepatitis. The findings are consistent with the `concentration-catabolism' effect. [ABSTRACT FROM AUTHOR]

The article focuses on the cost and benefits of biomedical research. Data on the cost benefits from basic and applied biomedical research indicates that benefits have exceeded the cost by 20-fold. Hence, cutbacks in funds for biomedical research represent fiscal irresponsibility. Everyone is aware about the funding of biomedical research in the past five years by the U.S. National Science Foundation, and reported allocations by the administration for the next fiscal year, have remained at more or less a constant level.

Using red cells sensitized with an IgG anti-Rh0 antibody, an IgG receptor was demonstrable on human monocytes, hepatic macrophage and splenic macrophage preparations. The receptor was uniformly lacking on lymphocytes, lymphoid cell lines and lymphocytes stimulated with phytomitogens in vitro. The integrity of this receptor was demonstrated on monocytes obtained from patients with ‘acquired’ agammaglobulinaemia, chronic granulomatous disease and acute monocytic leukaemia. There was no direct correlation between the presence of the receptor and the fine structure of the cells studied. It is proposed that this receptor is an immunological marker for identification of mononuclear cells. [ABSTRACT FROM AUTHOR]

Studies of the distribution of antibody-combining sites, anticomplementary and genetic activity in the papain digestion products of normal γ globulins and myeloma proteins have been carried out. The segregation of biological and chemical properties in the chromatographically separated fractions of the papain digests has been noted. Starch-gel electrophoretic studies indicate the complexity of the molecules of normal γ2 globulins and of myeloma proteins and indicate physico-chemical relationships between these types of molecules. Certain similarities in biological properties are also noted. [ABSTRACT FROM AUTHOR]

This article discusses whether immunology is science or septophrenia. This problem has been recognized in Great Britain and is being dealt with in a singularly intelligent fashion by creation of entire university departments of immunology or research institutes devoted to this discipline. Such synergistic collections of eminent immunologists are exemplified by the noted Department of Experimental Pathology here in Birmingham by the several excellent immuno-chemistry departments and research institutes in London, and by other departments and research institutes in the British Isles.

This article presents a case study on moniliasis, autoimmune polyendocrinopathy, and immunologic family study. A patient with chronic mucocutaneous moniliasis of 17 years duration developed bilateral keratitis, hepatitis and steatorrhea, conditions often found in association with coexistent adrenocortical and parathyroid insufficiency. Immunologic studies showed that the patient's serum contained organ-specific antibodies. Further clinical investigation demonstrated adrenal and thyroid insufficiency; parathyroid function was normal. Several investigators have suggested that the moniliasis is secondary to abnormal parathyroid function.

The article focuses on the univalency concept of the mechanism responsible for the failure of incomplete antibodies to produce direct agglutination of appropriate untreated red cells. The failure of incomplete or blocking antibodies to cause agglutination of erythrocytes containing the homologous antigen has been examined in recent investigations with active proteolytic fragments of rabbit and human antibodies. The various human antisera used in this investigation were obtained from donors in San Francisco Bay area. The results showed that the bivalent but not the univalent 7S and S materials produced significant direct saline agglutination of erythrocytes.

IgG-class iso-antibodies against human IgM ('reverse rheumatoid factors') were detected in titres from 1:4 to 1:1024 in the serum of twelve of forty subjects (30%) with selective IgA deficiency. The antibodies were detected in a haemagglutination system with red cells coated by the chromic chloride method with proteins from a panel including nineteen Waldenström macroglobulins. The forty subjects included seventeen normal subjects, ten with recurrent infections, seven with ataxia telangiectasia, two each with asthma and lymphoma and one each with rheumatoid arthritis and chronic active hepatitis. Four of the twelve positive sera contained 'class-specific anti-IgM' which reacted with all or most of the IgM coats. The eight sera containing 'anti-IgM of limited specificity' included six reacting with only one IgM coat, one reacting with two IgM coats and one reacting with four IgM coats. The anti-IgM in the latter serum defined an inherited allotypic marker on these four IgM proteins. There was no significant correlation between the presence of anti-IgM antibodies and the clinical status, sex and age of the patient nor the presence of antibodies against human IgG, human IgA and ruminant proteins. These antibodies against human IgM represent yet another immunologic abnormality in this group of patients. [ABSTRACT FROM AUTHOR]

Serum IgE levels in twelve patients with adult 'acquired' hypogammaglobulinaemia were markedly reduced. In addition, seventeen of fifty first degree relatives and spouses had low IgE levels. IgE levels varied among patients with selective IgA deficiency and a combined deficiency did not necessarily predispose to recurrent infections. This study suggests that the absence of IgE in certain immune deficiency states does not, by itself, decrease resistance to infection. [ABSTRACT FROM AUTHOR]

The in vitro cytotoxicity for fowl erythrocytes of circulating lymphocytes from nine patients with 'acquired' and three patients with sex-linked agammaglobulinaemia was tested by release of sodium chromate (51Cr) after 42 hr of culture in the presence of phytohaemagglutinin (PHA). The lymphocyte cytotoxicity of three patients with 'acquired' agammaglobulinaemia was low, but that of the other six and of the three patients with sex-linked agammaglobulinaemia were normal. All the 'acquired' agammaglobulinaemic patients had markedly diminished thymidine uptake in response to PHA at 3 days, but a normal response at 7-10 days, but the three boys with sex-linked agammaglobulinaemia showed a normal response. The findings further demonstrate the heterogeneity of lymphocyte abnormalities in patients with agammaglobulinaemia. [ABSTRACT FROM AUTHOR]