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Biomedical subjects

J F Miller

Publications and source records attributed to J F Miller.

At least 325 records · Page 18Linked to original sources
PubMed1976

A receptor for antibody on B lymphocytes. III. Relationship to immunoglobulin and ia determinants.

The physicochemical structure of the receptor for antibody (FcR) on B cells and its interrelationship with Ig and H-2 gene complex associated antigens were examined. FcR were found to be sensitive to treatment with phospholipase C and pronase, but resistant to neuraminidase, phospholipase A and chymotrypsin. They would therefore appear to be composed of phospholipoproteins. Several lines of evidence indicated that FcR and Ig receptors were discrete entities: thus, FcR (1) were resistant to chymotrypsin; (2) capped independently of Ig, as demonstrated by means of Fab fragments of anti-Ig, and (3) were closely associated with at least some Ia determinants, which are known to be distinct from Ig determinants. The relationship between FcR and H-2 gene complex associated antigens was confirmed by demonstrating inhibition of binding of aggregates by anti-Ia serum and vice versa. If, however, FcR were capped, anti-Ia serum applied under non-capping conditions was still found to bind diffusely to the great majority of B cells. Although this could be explained in part by the presence of residual FcR, some Ia determinants appeared to be distinct from FcR. The finding of residual FcR after capping with aggregates or immune complexes implied that FcR are a more integral part of the cell membrane than Ig receptors and could therefore act as proreceptors for the latter. Consistent with this was the demonstration of a significant polar distribution of Ig on B cells capped for FcR and then labelled under non-capping conditions with anti-Ig.

Animals↗
PubMed1975

Growth of B-lymphocyte colonies in vitro.

In semisolid agar cultures containing mercaptoethanol, cells from the spleen, lymph nodes, marrow, peritoneal cavity, thoracic duct, and blood of normal mice generated clusters and colonies of up to 3,000 cells. Colony numbers and growth were markedly enhanced by the addition of sheep red cells. The frequency of colony-forming cells in the spleen or lymph nodes was 0.5-2.0%, and cluster forming cells were approximately five times more numerous. The mononuclear cells comprising these colonies had the electronmicroscopic morphology of immature lymphoid and plasma cells. The majority of the cells possessed Fc receptors, 61-69% reacted with anti-mu-serum and 4-11% with anti-gamma2-serum. Analysis of single cells from individual colonies indicated a higher frequency of the cells with membrane immunoglobulin and a clonal pattern of anti-mu or anti-gamma-reactivity. The clonal nature of colonies was supported by an analysis of NIP-binding cells in colonies grown from CBA spleen cells enriched for NIP-binding cells. Mass-harvested colony cells synthesized immunoglobulin in short-term liquid cultures. It is concluded that the colonies are clones of functionally active B-lymphoid cells.

Animals↗
PubMed1975

Comparison of use of the Dalkon Shield in Dublin and Southampton.

The results of fitting Dalkon Shield I.U.D.s in Southampton and Dublin were compared. At 12 months the continuation rates were 77.4% and 93.4% respectively. There were also differences between the two cities in the major complication rates associated with the use of the device. At 12 months these rates for Southampton and Dublin were: pregnancy 5.6% and 1.4%, expulsion 4.0% and 0.9%, and removal for pain and/or bleeding 12.1% and 3.0%, respectively. Possible reasons for the difference in performance may include the older average age of the users in Dublin, and the greater number and more varied experience of the medical staff responsible for fitting in Southampton. We recommend that population factors be taken into account when comparing data relating to fertility regulation.

Adult↗
PubMed1975

Relationship between Fc receptors, antigen-binding sites on T and B cells, and H-2 complex-associated determinants.

The relationship between H-2 complex-associated determinants, Fc receptors, and specific antigen-recognition sites on T and B cells was examined by binding and functional assays. The Fc receptor was detected by radiolabeled immune complexes or aggregated human IgG. Both these reagents selectively bound to B cells, not to T cells. When spleen cells, from mice primed to several antigens, were exposed to highly substituted radioactive aggregates, their capacity to transfer both a direct and indirect plaque-forming cell response to these antigens was abrogated. Addition of B cells, but not of T cells, restored responsiveness. Complexed Ig binding to Fc receptors was prevented by pretreatment of mixed lymphoid cell populations with antisera directed against membrane components on the same cell (e.g., H-2) and on other cells (e.g., theta). The lack of specificity of inhibition was thought to be due to the formation on cell surfaces of antigen-antibody complexes which would then attach to the Fc receptor during the incubation precedure. Specific blockade of the Fc receptor during the incubation procedure. Specific blockade of the Fc receptor however occurred when B cells were pretreated with the Fab fragments of anti-H-2 antibody. This was demonstrated autoradiographically and by inhibition of aggregate-induced suicide. The blocking activity of ante-H-2 Fab was removed by absorption with spleen cells from thymectomized irradiated mice but not with thymus cells of appropriate specificity. This suggested that the antibodies involved had specificity for determinants on the B-cell membrane distinct from those coded by the K or D end of the H-2 complex, and either absent from, or poorly represented on, thymus cells. Specific antigen-induced suicide of B cells was achieved simply by incubating the cells with radioactive antigen in the cold. T-cell suicide on the other hand required that the 125I-labeled antigen be presented to the T cells at 37 degrees-C on the surface of spleen cells from antigen-primed mice. Pretreatment of T cells with the Fab fragment of anti-H-2 antibody protected them from the suicide effect. By contrast no such protection of B cells could be achieved by this procedure. In other words H-2 (? Ir)-associated determinants may not only be in close proximity to the antigen-binding site on T cells but, in addition, may be involved in the effective operation of the receptor.

Animals↗
PubMed1975

Significance of cellular interactions in the immune response.

Recent investigations relevant to T and B cell cooperation in humoral immunity are discussed from the following aspects: requirement for T cells in antibody responses; T cell facilitation of B cell responsiveness; T cell suppression of B cell responsiveness; evidence for a nonspecific influence of T cells on B cell responsiveness; relevance to clinical disorders.

Animals↗
PubMed1975

H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice.

Sensitized lymphocytes can transfer a state of delayed-type hypersensitivity to soluble protein antigens to naive mice only if donor and recipient share the I-A region of the H-2 gene complex. Identity at the K or D region is not essential. The restriction is unlikely to result from ineffective homing of the injected cells or from their early destruction. It is thought to reflect a requirement for an Ir-gene controlled mechanism which governs effective interaction between sensitized T lymphocytes and antigen presented on the surface of macrophages.

Animals↗
PubMed1975

Study of the Gregory blood group in an English family.

An example of anti-Gy-a found during routine antenatal testing is the first recorded example in Europe to be described. Five other Gy(a-) siblings were found in the patient's family from whom blood donations were obtained in the event of a needed transfusion. Although anti-Gy-a was detected in the infant's serum, there was no evidence of haemolytic disease of the newborn, presumably due to the fact that the Gy-a antigen is poorly developed at birth.

Blood Group Antigens↗
PubMed1975

A radioisotopic method to measure delayed type hypersensitivity in the mouse. I. Studies in sensitized and normal mice.

Delayed type hypersensitivity (DTH) lesions have been difficult to evaluate objectively in the mouse because they are usually assessed in terms of an increase in footpad swelling or ear thickness. We have developed a radioisotopic method which not only reduces the observer's error but also gives an objective measurement of the cellular activity in the lesions. In brief, 10 mul of the test antigen is injected intradermally into the left pinna and either nothing or the same volume of a control solution into the right. 10 h later, a 2-muCi pulse of 5-iodo-2'deoxyuridine-125I is given intravenously, the ears cut off at the hairline 16 h later and the radioactivity counted in a gamma spectrometer. The following was obtained as evidence that the increased radioactivity of the left pinna over the right was a measure of the extent of a DTH response: (1) the ear reaction was delayed in mice without serum antibodies becoming maximum at 24 h; (2) there was a mononuclear cell infiltration in the left pinna and autoradiographs revealed radioactive label bound to these cells; (3) athymic mice could not develop a 24-hour ear reaction, and (4) antigens known not to activate T cells did not elicit the ear response. Cell transfer studies will be described in a subsequent paper. Different sensitization regimes were required with different antigens in order to obtain the highest levels of DTH as tested by the ear response, and the maximal ear reaction occurred at different days. The ear reaction showed the specificity expected of a DTH response.

Animals↗
PubMed1975

A radioisotopic method to measure delayed type hypersensitivity in the mouse. II. Cell transfer studies.

Sensitized lymphoid cells could transfer to normal non-sensitized (naive) mice by 24-48 h after antigen challenge in the ear, the capacity to incorporate, at the site of antigen deposition, 5-iodo-2'deoxyuridine-125I in amounts significantly above those obtained in control mice. This was associated with a mononuclear cell infiltration in the pinna. In contrast to lymphoid cells, serum antibodies were unable to transfer a 24- or 48 hour ear reaction. The cells responsible were T lymphocytes as demonstrated by successful transfer following enrichment for T lymphocytes, and abrogation of transfer following treatment with anti-theta serum and complement. Transfer was achieved whether the naive recipients were normal, T-cell deprived, pretreated with cyclophosphamide, or lightly irradiated but not when they were heavily irradiated. Adoptive transfer of the 24-hour ear response was demonstrated with three different antigenic systems. The time-response curves were different with each system although peak reactions were obtained 5 days after sensitization of the donors in all cases. The specificity patterns of the 24-hour ear reaction on transfer were similar to those obtained in the sensitized donors. The results of these studies indicate that the radioisotopic ear method can, under defined conditions, demonstrate the existence of a state of delayed type hypersensitivity in the donors.

Animals↗
PubMed1975

Gastro-intestinal absorption and transplacental transfer of amoxycillin during labour and the influence of metoclopramide.

The absorption of amoxycillin from the gastro-intestinal tract, with or without oral metoclopramide, has been evaluated. Levels of amoxycillin in the maternal blood and liquor prior to the induction of labour were of a therapeutic level against many organisms. However, absorption during labour, as reflected by maternal blood levels at delivery and cord blood levels, suggests that amoxycillin is poorly absorbed and may not reach adequate therapeutic levels in the fetus. Oral metoclopramide did not improve the absorption of amoxycillin. Should a parenteral form of amoxycillin become available, a similar study of blood and liquor levels may indicate that, like ampicillin, intramuscular administration is required for adequate therapeutic use at this stage of pregnancy. Until an oral formulation of an appropriate antibiotic is available which gives rapid absorption may and a sustained level of the chemotherapeutic agent in this situation, parenteral administration of an appropriate antibiotic remains mandatory.

Amniotic Fluid↗
PubMed1975

A subpopulation of T cells bearing Fc receptors.

A wide range of cell populations were examined for Fc receptor (FcR)-bearing T cells: thymus, spleen, peritoneal cells, and T cells activated to H-2 antigens in spleen (ATC spleen) and in thoracic duct lymph (T-TDL). In addition, B lymphocytes from thoracic duct lymph of athymic nude mice and a Thy-1-positive, FcR-positive thymoma served as control cell populations. Reagents used were aggregates of human gamma-globulin and of various mouse myeloma proteins (IgG1, IgG2a, IgG2b), radioiodinated antigen-antibody complexes, and sheep erythrocyte antibody rosettes. Labeling techniques involving radioautography and immunofluorescence were used to demonstrate FcR by one of the above reagents and to identify T cells either by staining with anti-Thy-1.2 or by a specific rabbit anti-mouse T cell serum, or by failure to stain with anti-mouse immunoglobulin. In some experiments phagocytic cells were removed whereas in others they were identified by their capacity to engulf latex particles. Approximately 25% of cells with T cell markers were FcR-bearing cells in thymus, normal spleen, and peritoneal cavity, and 17% in ATC spleen. FcR on T cells in peripheral lymphoid tissues were detectable by aggregates of HGG and myeloma proteins and by radioiodinated immune complexes. Those on T cells in thymus were revealed only by aggregates of HGG. Circulating T cells (T.TDL) failed to display FcR: a) despite the use of a wide range of the above labeling techniques, each of which was shown to detect FcR on other T cells, thymoma cells, and B cells, and b) even after removal of Ig associated with their cell membranes. In contrast to B cell FcR which bound IgG1 preferentially, those on T cells bound both IgG1 and IgG2, raising the possibility that the FcR on T cell is distinct from that on B cell. It is concluded that FcR-bearing T cells represent a subpopulation of cells within the thymus and the secondary lymphoid tissues.

Animals↗
PubMed1975

Cellular basis of the immune response.

Lymphocytes, the cells competent to initiate immune responses, can be divided into two major groups: thymus-derived or T cells responsible for "cellular immunity" (e.g. delayed hypersensitivity reactions) and bursa (or bursa-equivalent) derived or B cells which produce immunoglobulin (antibody) molecules and are involved in "humoral immunity". "Accessory" cells, such as monocytes (or macrophages), polymorphonuclear leucocytes and mast cells act in an auxiliary manner by facilitating antigen processing or presentation, or by liberating factors which modify the various manifestations of the immune response. A variety of interactions between T and B cells and between lymphocytes and accessory cells have been described in both cellular and humoral immunity. Antigen-activated T cells produce factors with various activities: some are involved in recruiting inflammatory cells, others activate macrophages and enhance their microbicidal activities, and others modify B-cell responsiveness either by facilitating or suppressing it. These factors are instrumental in T-cell regulation of immune responsiveness. Antibody produced by B cells also plays a role in immuno-regulation, acting either as an immunopotentiating influence or as a negative feedback, e.g. when complexed with antigen, turning off the response of T or B cells. A detailed knowledge of the precise manner in which cells involved in immunity are regulated is essential for an understanding of how the foetus, an essentially "foreign transplant", can survive to term in its immunologically mature "alien" host.

Animals↗