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Biomedical subjects

B Daunter

Publications and source records attributed to B Daunter.

At least 37 records · Page 2Linked to original sources

The packing of spheres in embryogenesis and carcinogenesis.

Fertilization of the mammalian ova results in the formation of a compact ball of cells, the morula, which then transforms into a hollow sphere of cells, the blastula. The formation of these structures is considered to be dependent on the number and shape of the cells present and approximates to the problem of maximal sphere packing. Similarly, the shape of organs, to some degree, is considered to be dependent upon the shape of the constituent cells which predetermines their maximal packing densities. Implicit in this concept is that like-cells divide until they reach their maximal packing density and are then inhibited from further replication by three dimensional contact inhibition. In this context, tumour cells may be considered as pleomorphic relative to the tissue in which they arise and form a benign tumour, whereas malignant tumours display pleomorphism within the tumour mass.

Animals↗

RISH III. Haplotype-sharing in immune responses.

A number of hypotheses have been proposed for the reactivity of lymphocytes with allogeneic tissue. However, these hypotheses have not been generally accepted for they cannot accommodate the observation that lymphocytes from chimeras cooperate with each other. Also, only a few percent of lymphocytes react with allogeneic tissue in rejection reactions.

Animals↗

RISH V. Application to monoclonal antibody production.

RISH considers that cell surface components involved in like cell identification are not involved in the structure of the plasma membrane per se and are attached to a part of their mRNA. The mRNA then acts as a template for the synthesis of DNA. Thus the component at the cell surface is attached to an RNA/DNA receptor. If there is a conformational change in the component (antigen) this will cause a distortion in its RNA/DNA receptor. This distortion is then detected by a tissue specific T lymphocyte which removes all or part of the RNA/DNA receptor from the aberrant cell and the lymphocyte then undergoes replication. During this process receptor RNA/DNA is incorporated into the daughter lymphocyte which becomes a B lymphocyte/plasma cell producing immunoglobulin. The initial tissue specific T lymphocyte becomes a dual functional helper/suppressor cell. The plasma cell after the initial immune response becomes a circulating memory B cell displaying IgM or IgD. If this cell complexes an antigen with its surface IgM or IgD a humoral immune response will be developed as previously described, but in this case the antibodies produced will be anti-idiotypic antibodies. The anti-idiotypic antibodies will regulate the production of the antibody directed against the antigen per se. The anti-idiotypic antibodies will in turn be regulated by a second anti-idiotypic antibody. In RISH five such anti-idiotypic systems may be involved in regulating the immune response to the initial non-immunoglobulin antigen. Based on the RISH anti-idiotypic mechanism a system is briefly described whereby human memory B cells, to a particular antigen, may be isolated. These B cells may then be activated to secrete immunoglobulin with autologous isolated anti-idiotypic antibodies. These activated cells may then be infected with E.B. virus to establish an immortal cell line of B cells secreting the immunoglobulin of interest.

Animals↗

RISH IV. Immunoglobulin diversity.

RISH considers that cell surface components involved in like cell identification are not involved in the structure of the plasma membrane per se and are attached to a part of their mRNA. the mRNA then acts as a template for the synthesis of DNA. Thus the component at the cell surface is attached to an RNA/DNA receptor. If there is a conformational change in the component (antigen) this will cause a distortion in its RNA/DNA receptor. This distortion is then detected by a tissue specific T lymphocyte which removes all or part of the RNA/DNA receptor from the aberrant cell and the lymphocyte then undergoes replication. During this process receptor RNA/DNA is incorporated into the daughter lymphocyte which becomes a B lymphocyte/plasma cell producing immunoglobulin. The initial tissue specific T lymphocyte becomes a dual functional helper/suppressor cell. The B lymphocytes use the RNA from the RNA/DNA receptor to synthesize the variable region of the first antibody, IgM1. This antibody (IgM1) does not react with the antigen, ie. the distorted component, or the receptor RNA, but with receptor DNA. The DNA of the receptor base pairs with its complementary strand in the B lymphocyte, and the complementary DNA acts as a template for mRNA synthesis. This results in the production of IgM2 and IgG that can bind the antigen and receptor RNA. These antibodies (IgM1, IgM2 and IgG) when endocytosed by the stimulating cell will also complex cytoplasmic mRNA and nuclear DNA and prevent the synthesis of the antigen that initiated the immune response. If other classes of antibodies are to be produced they will follow a similar pattern (IgM1, IgA and IgG or IgM1, IgE and IgG). From the codons of the known amino acids, the codons for amino acids from translation of the complementary DNA strand have been calculated. The amino acids derived from the complementary codons are considered to represent sequences of amino acids in the antigen as represented by the DNA of an RNA/DNA receptor. For these sequences of amino acids, each has a complementary amino acid as defined by the normal codon. These complementary amino acids are then used in the synthesis of the variable region of the antibody.

Amino Acid Sequence↗

Melphalan-resistant lymphoblastoid cell lines established from patients with ovarian cancer treated with cross-linking agents.

Lymphoblastoid cell lines (LCLs) were established from 83 patients with ovarian cancer by transformation of peripheral B lymphocytes with Epstein-Barr virus. Comparing the melphalan resistance of different groups of LCLs using the mean Do obtained from clonogenic survival assays, LCLs from melphalan-treated patients were significantly more resistant than LCLs from patients not treated with this drug. However, prior treatment of the patient with ionizing radiation was not associated with increased in vitro resistance of the LCL to this agent. In melphalan-treated patients where LCLs were established serially, the melphalan Do increased after further melphalan treatment in vivo and decreased when no further treatment was given. No correlation was found between age of donor and LCL resistance to any of the above agents. A group of 15 LCLs previously established from non-tumour donors was less resistant to melphalan than the LCLs from patients with ovarian cancer. In a group of 29 patients with advanced disease in whom the clinical response was known, LCL resistance to melphalan appeared to be associated with poor clinical response to cross-linking agents. These results suggest that B cell populations undergo long term, but not necessarily permanent, increases in resistance to melphalan.

B-Lymphocytes↗

Role of cervical mucus in human infertility.

The physiological role of cervical mucus in enhancing spermatozoal penetration at mid-cycle has been established. However, the involvement of cervical mucus in primary infertility is still controversial. Although immunological reactions against spermatozoa in the female have been offered to account for the immobilization of spermatozoa--an observation termed 'hostility' of the mucus--this is not always demonstrable. In addition, there are a number of microbial antigens that are similar to spermatozoal antigens. Antibodies to these antigens are found in the serum of the majority of females and males whose infertility is considered to be immunopathological in origin. There are also naturally-occurring antispermatozoal antibodies in both females and males that in some cases may contribute to immunological infertility. The overall spectrum of 'hostile' mucus reactions becomes more complex when we consider the biochemical structure of cervical mucus and its possible interaction with spermatozoa. This spermatozoa: mucus interaction may involve the transfer of spermatozoal components to 'hostile' mucus that should normally be transferred to the zona pellucida of the ova. In addition, there are also pH changes in some 'hostile' mucus that lead to spermatozoal immobilization. In contrast to the above, the cause of infertility in some cases is the inability of spermatozoa to survive in normal mid-cycle mucus. It is evident therefore that an understanding of the complex nature of 'hostile' cervical mucus will lead to a more objective approach in the treatment of infertility.

Antibodies↗

Immune complexes in ovarian cancer: association between IgM class complexes and antinuclear autoantibodies in ascitic fluid.

Samples of ascitic fluid from patients with ovarian cancer were analyzed for autoantibodies to nuclear and cytoplasmic antigens and for immune complexes (ICs) detectable by the Clq deviation and polyethylene glycol (PEG) precipitation (either IgG or IgM class) assays. The predominant autoantibody was antinuclear (ANA); this was detected in 29 of 58 samples (59% showing the homogeneous and 41% the speckled pattern). The antibody was not reactive to saline extractable nuclear antigens. A strong association between this autoantibody and the PEG-precipitated IgM class ICs was shown, suggesting the possible participation of this autoantibody in IgM class ICs formation. The lack of association between C1q-reactive and IgG class ICs and the autoantibodies indicates that the IgG class ICs may be more related to the tumor.

Adult↗

Demonstration of tumor-associated immunoglobulin G isolated from immune complexes in ascitic fluid of ovarian cancer.

An analysis was made of the ascitic fluid obtained from a patient with serious cyst-adenocarcinoma of the ovary. The fluid contained no reactivity to rheumatoid factor, carcinoembryonic antigen, and autoantigens. The immune complexes in the ascitic fluid, demonstrated by C1q deviation and characterized by gel chromatography, protein A binding studies, and Ouchterlony diffusion, appeared as high molecular weight material. The monomeric IgG dissociated from this material was capable of reassociation into complexes, as shown by radioactive labelling studies. The IgG isolated from the complexes was localized specifically to autologous as well as heterologous malignant ovarian tumor cells but not to normal ovarian tissue by the immunoperoxidase technique.

Antibodies, Neoplasm↗

Biochemical and functional-structural aspects of human cervical mucus.

Human cervical mucus is composed of an insoluble polymer of glycoproteins (mucin) which forms a matrix in which the aqueous phase is dispersed. Both the mucin and the aqueous phase are considered to be of importance to the structural integrity and function of cervical mucus. The mucin is considered to be composed of coiled glycoprotein molecules. These molecules may then associate by the chelation of divalent copper, via the carboxylic acid groups of the terminal sialic acid moieties of the carbohydrate side chains, to form the mucin per se. The modulation of the mucin structure at midcycle may then be achieved by the reduction of the copper bound to the sialic acid, by the oxidation of L-ascorbic acid: the L-ascorbic acid becoming oxidized to dehydroascorbic acid. This will result in an increase in hydration of the mucin by the association of water molecules with the uncomplexed sialic acid molecules of the glycoproteins. Thus the biophysical changes of cervical mucus may occur without enzymatically induced biochemical reactions. The proposed biochemical structure of cervical mucus is in accordance with the honeycomb-like structure of cervical mucin viewed by scanning electron microscopy. Whether or not the mucin exists precisely in this form in vivo is debatable. However, the honeycomb-like structure provides a convenient model on which one may investigate the biochemical, physiological and pathological nature of cervical mucus.

Ascorbic Acid↗

Affinity chromatography separation of tumor associated antigens from ascitic fluid of ovarian cancer patients.

Tumor associated immunoglobulins previously isolated from ovarian cancer ascitic fluid have been used in an affinity chromatography step to purify putative tumor associated antigens from a perchloric acid extract of ascitic fluid. Examination of the affinity chromatography purified proteins revealed 4 bands on electrophoresis. Antisera raised to the affinity chromatography products have been examined by Ouchterlony diffusion as well as a solid-phase radioimmunoassay. Two of thirteen ovarian tumor extracts investigated reacted in Ouchterlony diffusion analysis, whereas all thirteen extracts gave positive results in the more sensitive solid-phase radioimmunoassay.

Antigens, Neoplasm↗

Types of immune complexes in the ascitic fluid of women with carcinoma of the ovary.

Immune complexes with C1q-fixing properties and those precipitable by polyethylene glycol (PEG) were detected in ascitic fluid from patients with advanced ovarian cancer. The ascitic fluid from 42 of 58 patients (72%) contained these complexes. A positive result with the C1q assay was obtained in 41% of patients, whilst with the PEG assay a positive result was obtained in 59% (50% in the IgM, 36% in the IgG, and 14% in the IgA fraction). The highest mean level of PEG-precipitable complexes was in the IgG fraction (11.4 mg/100 ml) and lowest in the IgA fraction (3.3 mg/100 ml). These results indicate that gram quantities of the immune complexes may be isolated from the large volumes of ascitic fluid usually present in ovarian cancer. Further studies of ascitic fluid may thus provide data on the nature of the immune responses in these patients.

Antigen-Antibody Complex↗

Immunoglobulins reactive to carcinoembryonic antigen and their relationship to the antigen in malignant ascitic fluid of ovarian carcinoma.

Samples of malignant ascitic fluid from 30 patients with advanced ovarian carcinoma were examined for the presence of IgM antibodies to CEA and PEG-precipitable proteins binding to 125I-CEA. The IgM antibodies to CEA were measured by a solid-phase radioimmunoassay using ovarian CEA. There was no correlation between the level of IgM antibodies to CEA and that of total IgM in the fluid. In 11 of 30 (37%) samples tested, significant amounts of IgM antibodies to CEA were found. The CEA-binding proteins were measured by the ability of ascitic fluid to incorporate 125I-colonic-CEA into PEG-precipitable complexes. In 9 of 39 (30%) samples, the precipitation was significant. There was no association between antibodies to the ABO and Lewis blood group factors and these antibodies to CEA. An inverse relationship was observed between the level of CEA and that of CEA-binding proteins shown by the two assays. When 125I-CEA was incubated with these "positive" samples, a high molecular weight fraction was demonstrated by chromatography. By contrast, in the "negative" samples, there was no incorporation of 125I-CEA. These findings would indicate the presence of CEA-reactive proteins possibly existing as immune-complex-like material in ascitic fluid of some patients.

ABO Blood-Group System↗

Infertility: cervical mucus and semen factors.

A total of 34 infertile couples whose infertility was considered to be the result of a cervical factor were investigated. The use of pooled human blood plasma was found to significantly stimulate spermatozoal motility relative to that in seminal plasma or tissue culture media. Two additional male factors that may contribute to infertility have been identified, nondirectional spermatozoal motility, and in particular the inability of spermatozoa from some males to survive in normal donor mucus. This is supported by the fact that pregnancies only occurred in those cases (25%) in which the spermatozoa were able to survive in normal donor mucus. These pregnancies were achieved by artificial insemination using the husband's spermatozoa suspended in pooled human blood plasma.

Blood↗