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K James

Publications and source records attributed to K James.

At least 253 records · Page 14Linked to original sources

Distribution of IgM, IgA and IgG secreting cells in the tissues of normal and tumour-bearing mice.

The levels of IgM, IgA and IgG secreting cells were examined in control, Corynebacterium parvum-stimulated and tumour-bearing, normal and athymic (Nu/Nu) mice. The percentage of IgA to IgM or IgG secreting cells is relatively higher in peripheral blood than in the spleen or peritoneum of normal mice. Within tumours, irrespective of their degree of vascularization and immunogenicity, the pattern of Ig secreting cells in similar to that seen in peripheral blood and different from that in spleen and peritoneum even in athymic mice. Intraperitoneal injection of C. parvum changes the relative percentages of Ig secreting cells in the peritoneal cavity to resemble that seen in the peripheral blood and tumours. It appears that Ig secreting cells extravasate from peripheral blood in a non-isotype specific manner into sites of chronic stimulation.

Animals↗

Inhibition of lung metastases in mice bearing a malignant fibrosarcoma by treatment with liposomes containing human C-reactive protein.

Recent studies suggest an immune modulator role for C-reactive protein (CRP). We have tested the effect of CRP in a tumor system designed for study of metastases. Fibrosarcoma T241 was implanted on one hind foot of syngeneic C57BL/6 mice. After 17 days, the tumor-bearing feet were amputated, and i.v. therapy of liposomes containing CRP or control reagents was started. Examination of the lungs on Day 35 showed that CRP:liposome-treated animals had significantly fewer and smaller metastases as compared with those in the control groups. Moreover, 38% of the animals in the former groups were completely free of metastases as compared with 0 to 2% of the controls. Significantly, enhanced survival was also noted in the CRP liposome-treated group. CRP may have biological response modifier" function of value in cancer therapy.

Animals↗

Immunological and biochemical characteristics of acid citrate eluates from tumour cells: a major non-immunoglobulin component.

Using competitive double-antibody radioimmunoassays we have shown that immunoglobulin (especially IgA) can be recovered in pH 3.5, 0.12M acid citrate eluates of freshly excised CCH1 tumour-cell suspensions. Studies with 125I-labelled eluates indicate that such preparations exhibit a variable, but appreciable, degree of non-specific binding to unrelated syngeneic tumour and normal tissues. PAGE/SDS gel electrophoresis of the labelled eluates revealed the presence of a major non-immunoglobulin component of 33-36K dalton which could account in part for the non-specific binding observed. This component was also detected in similar eluates from cultured CCH1 tumour and in all other tumour-cell eluates examined to date. In contrast, preliminary data suggest that it is less prevalent in acid citrate eluates from normal tissue, with the exception of peritoneal-exudate cells. The possible origins, nature and significance of this non-immunoglobulin component are discussed.

Animals↗

Binding of C-reactive protein to human lymphocytes. I. Requirement for a binding specificity.

Our laboratory previously reported that C-reactive protein (CRP) binds selectively to T lymphocytes and inhibits certain of their reactivities in vitro. However, these findings could not be repeated using more highly purified CRP preparations even under a variety of experimental conditions. Purified CRP alone did not bind to peripheral blood lymphocytes (PBL); however, in the presence of a ligand such as pneumococcal C-polysaccharide (CPS), CRP binding was readily detectable both by immunofluorescence and by a radioassay established for this purpose. The optimal concentration of CRP, ratio of CRP:CPS, and time and temperature for reactivity were determined using both assays. A markedly enhanced rate of binding was observed after pre-equilibration of CRP with calcium. A small percentage (mean 3.0%; range 0.5 to 8.0%) of PBL bound complexed CRP, and saturation was reached with 200 microgram CRP/ml. Reactivity of CRP with a multimeric form of phosphocholine (PC) (KLH-PC44) led to binding comparable to that observed with CPS, whereas monomeric PC inhibited the binding. Thus, in the presence of a multimeric binding specificity, CRP binds to a small fraction of peripheral blood lymphocytes, which are characterized in the accompanying paper.

Binding Sites↗

Binding of C-reactive protein to human lymphocytes. II. Interaction with a subset of cells bearing the Fc receptor.

In the preceding paper we reported that C-reactive protein (CRP) in the presence of a multimeric binding specificity such as C-polysaccharide (CPS) binds to a small percentage of peripheral blood lymphocytes (PBL). In the present paper additional methods for demonstrating this binding were developed and utilized to help characterize the CRP-binding cell. Heat-modified CRP and E-CPS-CRP each were found to bind to a similar percentage of PBL by microscopic visualization, and an identical degree of binding was observed by cytofluorimetric analysis. Multiple marker studies indicated that CRP-binding cells are found in the T cell, B cell, and null cell categories in a ratio of 2:1:1, respectively. Preferential overlap was seen with IgG FcR-bearing cells, which accounted for 70% of the CRP-binding cells; however, only 12% of the FcR cells bound CRP. These studies indicate that CRP-binding cells predominantly represent a subset of cells bearing FcR, and these cells have the morphologic characteristics of large granular lymphocytes. CRP in the presence of CPS bound to cells of multiple human and murine cultured lines shown to have IgG FcR reactivity, but showed lesser or no binding to cell lines negative for FcR. The precise morphologic and functional characterization of the CRP-binding cells and the nature of the binding site are yet to be established.

Binding Sites↗

Effects of therapy on carcinoembryonic antigen activity in the urines of patients with cancer of the bladder.

Carcino-embryonic antigen (CEA) levels were quantitated in specimens of urine for 16 patients with invasive transitional-cell carcinoma of the urinary bladder. Four of the patients had received x-irradiation to the bladder and four had been treated with the radiomimetic agent, thiotepa. Urinary CEA levels in these patients (3.7 +/- 2.4 ng/ml) were significantly lower (t = 6.17, P less than .001) than levels from a similar group of eight patients who had not been treated with radiotherapy (20.3 +/- 8.7 ng/ml). These results suggest that "false-negative" urinary CEA levels may, in some cases, be associated with previous radiotherapy.

Carcinoembryonic Antigen↗

Serum alpha 2-macroglobulin levels in diabetes.

Serum alpha 2-macroglobulin levels have been determined in diabetic patients by quantitative radial immunodiffusion and compared with those observed in age- and sex-matched controls. In addition, the results in diabetics have been analysed with respect to such variables as the age and sex of the patient, the duration of disease, treatment, control, and the occurrence of retinopathy or nephropathy. The alpha 2-macroglobulin levels in diabetic patients were found to be significantly higher than in age- and sex-matched controls, thus confirming previous observations. However, these differences were most apparent in the more extreme age groups. Multiple regression analysis also revealed that the only variables contributing significantly to the regression apart from age and sex were control and retinopathy.

Adolescent↗

Further studies on antitumour responses induced by short-term pretreatment with syngeneic tumour cells.

The ability of s.c. injected tumour cells to specifically inhibit the growth of similar cells injected i.v. 2 days later has been confirmed. The capacity of tumour cells to elicit this effect varies form tumour to tumour. Furthermore, it is more readily achieved with cultured than with freshly excised tumour cells. The superior effect elicited by cultured tumour cells was not overcome by treating them with trypsin or pronase. The protection achieved was impaired in T-cell-depleted mice and mice which had been irradiated (400 rad) prior to pretreatment. In contrast, it was not affected by administration of silica, sodium aurothiomolate or cortisone acetate. The results imply that T-cell-dependent responses are involved in the protection conferred by pre-injecting tumour cells shortly before i.v. challenge.

Adenocarcinoma↗

Association of host immunoglobulins with solid tumours in vivo.

Using a direct radioimmune antiglobulin technique and a competitive double-antibody radioimmune assay, we have demonstrated the presence of appreciable amounts of host immunoglobulins on the surface and in extracts of cell suspensions from freshly excised solid tumours. IgA appeared to have the greatest concentrations from freshly excised solid tumours. IgA appeared to have the greatest concentration, followed in turn by IgM congruent to IgG2a greater than IgG1 congruent to IgG2b greater than IgG3. The amount of immunoglobulin appeared to be influenced by the tumour under investigation and its mode of maintenance. It could also be increased by the administration of C. parvum but was not significantly influenced by the T-cell status of the host.

Animals↗

Antitumour responses induced by short-term pretreatment with tumour cells.

The injection (s.c. or i.p.) of 10(6) live or lethally irradiated methylcholanthrene-induced fibrosarcoma cells into CBA/Ca mice one or 2 days before i.v. challenge with the same tumour inhibited the formation of artificial lung tumour metastases. In addition, it also frequently enhanced the cytostatic effect of peritoneal exudate cells on monolayers of the same tumour. The effects on lung tumour metastasis were not noted if X-irradiated tumour was injected i.v., or if s.c. administration was delayed until one day after i.v. challenge. Similar effects on tumour growth were also observed in C3Hf/Bu mice and (CBA/Ca x A/HeJ) F1 hybrids which were pretreated (s.c.) with tumour shortly before i.v. challenge with the same tumour. Further studies in CBA/Ca mice suggested that the protective effect was tumour-specific, for the growth of i.v. injected tumour was not significantly inhibited by pretreatement with a number of other MC-induced or spontaneous tumours from the same and different strains.

Animals↗

Studies on the Fc receptor bearing cells in a transplanted methylcholanthrene induced mouse fibrosarcoma.

The presence of Fc receptors on the surface of cell suspensions obtained from a transplanted isogeneic methylcholanthrene induced murine fibrosarcoma has been investigated by determining the capacity of such cells to form rosettes with antibody coated SRBC. These studies indicate that a large percentage of cells in the tumour had Fc receptors on their surface. The proportion of such cells was increased by reducing the number of cells transplanted, by administering cyclophosphamide to the host, and on occasions by the i.p. injection of C. parvum. It was largely unaffected by the route of tumour cell transplantation or by T cell depletion of the host before transplantation but appeared to decline in older (i.e. larger) tumours. Both phagocytic and non-phagocytic cells had Fc receptors on their surface. The phagocytic population appeared to be affected most by procedures which altered the overall percentage of Fc receptor bearing cells. The Fc receptor bearing tumour cells were separated from those devoid of Fc receptors on the basis of their adherent properties. Upon transplantation to isogeneic hosts both populations gave rise to tumours containing a high percentage of Fc receptor bearing cells. These studies suggest that many of the Fc receptor bearing cells in our tumour are probably infiltrating cells of host origin. Their significance in relation to tumour growth remains to be established.

Animals↗

Antitumor antibodies and immunoglobulin class and subclass levels in Corynebacterium parvum-treated mice.

Changes in immunoglobulin class and subclass levels and the development of antitumor antibodies were assessed in normal and tumor-bearing mice challenged with Corynebacterium parvum. C. parvum administration resulted in a marked increase in certain immunoglobulin levels, especially Ig G2b, and in the development of antibodies reacting with syngeneic and allogeneic tumor cells. The serologic changes induced by C. parvum were dependent on the dose and route of administration; preliminary studies suggested that they may have been largly independent of T-cell function. These changes were suppressed by the administration of gold salts, which also inhibited the antitumor effect of C. parvum.

Animals↗

New allele at cholinesterase locus 1.

A family (H-J pedigree) segregating for the A and F alleles at cholinesterase locus 1 is described. Apparent anomalous results led to the recognition of a new allele (E1j) also segregating in the family. The data are consistent with the hypothesis that the the E1j causes reduction of 'usual' (E1u) molecules by about 66%. Whether this is because of retarded synthesis or accelerated degradation of serum cholinesterase remains to be determined.

Alleles↗

The effect of Corynebacterium parvum therapy on immunoglobulin class and IgG subclass levels in cancer patients.

Detailed serological studies have been undertaken in a small group of cancer patients receiving nonspecific immunotherapy with Corynebacterium parvum (C. parvum). These patients included 4 cases of recurrent malignant melanoma, 2 of stomach cancer and 2 of recurrent breast cancer. They all received an initial i.v. infusion of 20 mg of a formol killed suspension of C. parvum followed by 2 mg (i.m.) at weekly intervals for 10-11 weeks. This protocol consistently resulted in an increase in the circulating IgG levels of all patients but had a variable effect on their IgA, IgM and IgE levels. Increases in the concentration of all 4 IgG subclasses contributed to the overall increase in IgG levels and these changes ranked IgG2 greater than IgG1 greater than IgG3 = IgG4. It also had an inconsistent effect upon the levels of alpha-macroglobulin in pregnancy but the levels of normal serum alpha2-macroglobulin were virtually unchanged. Pre-existing antibodies to C. parvum were noted in all the patients. Titres rose appreciably following C. parvum administration and remained at high, though fluctuating levels, throughout the 100-day period of observation. Absorption studies suggested that the development of antibodies to C. parvum accounted in part for the increased IgG levels noted following this form of therapy. The significance of these changes in relation to the possible anti-tumour effect of C. parvum is discussed.

Adult↗