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Biomedical subjects

K James

Publications and source records attributed to K James.

At least 163 records · Page 9Linked to original sources
PubMed1990

Cell surface phenotype, cytokines, and antibody gene expression in immortalized human B cell lines.

In an attempt to gain some insight into the many factors influencing antibody gene expression in human B cell lines, we have examined in detail the relationship between cell surface phenotype, cytokines, and the growth and antibody-producing capacity of a panel of immortalized human B cell lines. The cell panel comprised lines secreting either high or low titers of antibodies against Rhesus D, hepatitis B surface, and tetanus toxoid antigens. All the transformed cell lines exhibited a cell surface phenotype characteristic of well-differentiated peripheral blood cells strongly expressing CD23 and CD38 while weakly expressing CD10 and CD21. There was no obvious relationship between the antibody-body-secreting and proliferative capacity of the cell lines and their cell surface phenotype. Antibody secretion by the cells was rarely improved by the addition of a wide range of doses of recombinant IL-2, IL-4, or IL-6. In addition, such treatment frequently inhibited proliferation. Supernatants from some of the cell lines promoted the growth of unrelated cell lines but failed to influence antibody production. Such supernatants contained the highest concentration of IL-1, TNF beta, TGF beta, and soluble CD23. In contrast, the heterohybrid supernatant which inhibited cell growth secreted low levels of these cytokines. None of the cell lines secreted detectable amounts of IL-2, IL-4, INF gamma, or GCSF. There was no obvious relationship between cytokine production and antibody secretion. Finally, LPS had a slight but variable effect on antibody secretion but failed to influence cell growth.

Antibody Formation↗
PubMed1990

Human monoclonal antibodies and engineered antibodies in the management of cancer.

In an attempt to obtain more specific and less immunogenic monoclonals for cancer therapy considerable effort has been devoted to the development of human monoclonals. Although this has resulted in the generation of many antibody secreting cell lines they rarely produce useful levels of specific antitumour antibodies. An alternative approach is the humanisation of rodent antitumour monoclonals using genetic engineering techniques. The chimaeric antibodies produced may exhibit reduced immunogenicity and improved Fc mediated interactions. Finally a number of procedures have also been employed to generate so-call bispecific monoclonal antibodies which offer novel therapeutic possibilities.

Antibodies, Monoclonal↗
PubMed1990

Immunosuppression by seminal plasma and its possible biological significance.

The data support the role of seminal plasma facilitating the transmission of virus and establishment of infection when all depositions of semen occur, but systemic absorption would also be possible by vaginal intercourse if lesions or abrasions caused for example by other s.t.d's, were present. The severity and rapid increase in the population of certain sexually transmitted agents make it imperative that epidemiological studies are initiated to study any correlation with changes in sexual behaviour and contraceptive practices. Finally, further isolation and characterization of seminal plasma components should lead to a clear understanding of their action as both regulatory molecules and in their possible contribution to disease.

Humans↗
PubMed1989

UK-69,578, a novel inhibitor of EC 3.4.24.11 which increases endogenous ANF levels and is natriuretic and diuretic.

A search for potent inhibitors of EC 3.4.24.11, an enzyme which is found most abundantly in the kidney and which degrades atrial natriuretic factor, has led to the identification of UK-69,578. Structure-activity studies starting from substituted N-carboxymethyl dipeptide inhibitors resulted in the introduction of a cyclo-alkane P1' residue and in the replacement of the aza-link between P1 and P1' residues by a methylene group, with a net ten-fold potency gain. UK-69,578 increases endogenous ANF levels and produces natriuretic and diuretic responses intravenously in mice.

Animals↗
PubMed1989

Human atrial natriuretic factor (ANF). Characterisation of a monoclonal antibody panel and its use in radioimmunoassay.

The production of nine monoclonal antibodies to human atrial natriuretic factor (ANF 1-28) is described. All possible combinations of two antibodies failed to reveal any which could simultaneously bind ANF. Studies with ANF analogues and the antibodies having the three highest affinity values (KD = 5, 25 and 21 pM) indicated that the antibodies are directed to the central portion of the antigen molecule. The highest affinity antibody was able to replace polyclonal antisera in the radioimmunoassay of ANF in extracts of plasma.

Antibodies, Monoclonal↗
PubMed1989

HLA-DR expression by high grade superficial bladder cancer treated with BCG.

The local immune response to intravesical BCG therapy for widespread carcinoma in situ and superficial bladder tumour was assessed using immunohistochemical methods on serial biopsies obtained during treatment. The main findings were the induction of a strong level of HLA-DR expression by urothelial cells which persisted for several months after completion of therapy. This coincided with a mononuclear cell infiltrate in the bladder wall consisting predominantly of activated helper T lymphocytes. Smaller numbers of macrophages, suppressor cytotoxic T lymphocytes and B lymphocytes were also found. These new findings confirm that the inflammatory response to BCG involves the urothelium in an immunological reaction and suggest that the success of immunotherapy with intravesical BCG may be due to enhanced tumour antigen recognition.

Administration, Intravesical↗
PubMed1989

Early post-operative morbidity of total prostatectomy.

Complications were analysed in a contemporary series of 100 total prostatectomies performed, for carcinoma of the prostate, under the supervision of one surgeon. There were 7 major complications including 1 death. No patient had a rectal injury. Minor complications occurred in 33 patients. Severe stress incontinence persisted in only 2 patients and 12 had minor stress incontinence. Of 38 patients potent before surgery and in whom it was possible to preserve both "neurovascular bundles of Walsh", 45% retained post-operative potency. Preservation of potency was related to the pathological extent of the tumour. It was concluded that in selected patients, total retropubic prostatectomy can be performed safely with good quality of post-operative life.

Adenocarcinoma↗
PubMed1989

Reactivation of antibody genes in Epstein-Barr virus transformed human B cell lines. A preliminary report.

Three immortalised human B cell lines, which had either last their capacity to secrete specific antibody or secreted low levels of antibody were studied in an attempt to reactivate or enhance antibody synthesis. A variety of different stimuli known to cause activation, proliferation and differentiation of normal B cells were used including polyclonal activators and recombinant interferon. Four of them, (namely LPS, anti-IgM, IL2 and IL6) effectively increased specific antibody synthesis after three days of culture. These preliminary experiments show that the loss or decline in immunoglobulin production by immortalised human B cells is, at least in some cases, reversible.

Antibody Formation↗
PubMed1989

Immunosuppression by seminal prostaglandins.

In this paper we report studies undertaken to determine the contribution of seminal prostaglandins to some of the known immunosuppressive properties of human seminal plasma. Initial studies revealed that fractions of seminal plasma enriched in E series prostaglandins, obtained by reverse phase chromatography, had a pronounced inhibitory effect on the PHA-induced proliferation of peripheral blood lymphocytes and on the NK-cell-mediated lysis of K562 target cells. Additional investigations revealed that similar inhibitory effects could be achieved with purified PGE2 (10(-6) to 10(-9) M) and 19-OH PGE1 (10(-6) to 10(-7) M), both of which are present in uniquely high concentrations in human seminal plasma. In contrast, 19-OH PGF1 which is found in lower concentrations in semen was slightly stimulatory in proliferative assays and had no effect on NK-cell-mediated cytotoxicity. Removal of the seminal prostaglandins by absorption chromatography resulted in a dramatic decrease in immune suppressive activity. Further studies with fractions obtained by ion-exchange HPLC of desalted seminal plasma indicated that prostaglandins complexed with seminal proteins, and these too were immunosuppressive. The possible relevance of these results to sexually transmitted disease is discussed.

Cytotoxicity, Immunologic↗
PubMed1988

Production and use of human monoclonal anti-D antibodies.

Rhesus haemolytic disease of the newborn is a condition which can result in intrauterine or perinatal death. Although the passive administration of therapeutic anti-D post-partum is a most effective method for the prevention of this condition, there is currently a shortage of immune plasma for the preparation of the therapeutic anti-D immunoglobulin product. In addition the availability of anti-D for use in blood grouping has also been reduced. The advances made in recent years in the techniques for the production of human monoclonal antibodies raise the possibility that human monoclonal anti-D-based products may provide solutions to both of these problems. There are now a number of reports of the production of stable cell lines secreting high titre human anti-D. In this review we consider the various strategies used in the production of human monoclonal anti-D-secreting cell lines, the basic properties of these reagents and their potential usefulness in blood grouping, in therapy and as research tools.

Antibodies, Monoclonal↗
PubMed1988

Breast tumour of pregnancy ('lactating' adenoma).

Fourteen cases of a benign lesion of the breast, often referred to as 'lactating' adenoma, are described. They were all first noticed during pregnancy. The microscopic changes are similar to those seen in the normal pregnant breast but vary in degree and are out of phase with it. Any association with fibroadenoma or fibrocystic disease seems coincidental. 'Lactating' adenomas are also clearly distinguishable from tubular adenomas, which consist of masses of closely set tubules, like ductules of the normal resting breast, and are not related to pregnancy. Immunocytochemistry using antisera to breast and tumour associated antigens can demonstrate clear differences between 'lactating' adenoma, other breast lesions, and the normal pregnant breast. A plea is made for the designation of these lesions as 'breast tumour of pregnancy' as they do not arise in the lactating period.

Adenoma↗