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Biomedical subjects

E C Krishnan

Publications and source records attributed to E C Krishnan.

At least 37 records · Page 2Linked to original sources

Morphological studies of peripheral monocytes during in vitro maturation by scanning electron microscopy.

Human peripheral monocytes were cultured in autologous serum over a period of 14 days. Morphological changes were observed in both light and scanning electron microscopy. Nonspecific esterase, Fc receptor, and phagocytic activities were studied using antibody-coated sheep erythrocytes. Though the spreading of cytoplasm was observable in a light microscope, scanning electron microscopic pictures revealed several interesting changes during the culture period. The number of filopodia and microvilli increased as the duration in cultured increased. At the end of 7 days, almost pure monocytes remained in culture. These cells were characteristically 98-100% nonspecific-esterase positive, Fc-receptor positive, and highly phagocytic. This technique may be of value in understanding changes due to various specific and nonspecific immune stimulators.

Cell Differentiation↗

Quantitative studies of monocyte maturation in patients with malignant melanoma.

Peripheral blood monocytes were cultured from normal volunteers and patients with malignant melanoma in a suspension culture containing 50% autologous plasma. The number of monocytes that matured into macrophages in the normal control population was 8.29 +/- 3.14 X 10(4) cells/ml blood, whereas in patients with malignant melanoma the number of matured monocytes was 3.15 +/- 2.80 X 10(4) cells/ml blood. The low macrophage maturation in patients with malignant melanoma was not found to be associated with any serum factors. Furthermore, from morphological studies done using scanning electron microscopy, there was no apparent difference between macrophages maturing from normal individuals or patients with malignant melanoma. From analysis of this adherent cell population there appears to be an intrinsic defeat in the maturation of monocytes in vitro in the case of patients with malignant melanoma.

Adult↗

Immunoglobulins and immunoglobulin receptors associated with human malignant tumors.

Over the past five years 86 malignant tumors were assayed for cell surface IgG, elutable Ag-Ab complexes, and/or cell surface Fc receptors. Surface IgG was measured by indirect radioimmunoassay, using single-cell suspensions and tumor eluates. Fc receptors in tissue sections were identified by the closed chamber technique. The results confirm our previous finding that human tumors are coated in vivo with IgG and that there is a population of cells within solid tumors capable of binding Ag-Ab complexes. In addition, Ag-Ab complexes appear to attach to the cell surface membrane by the Fc zone of antibody. Ag-Ab binding was inhibited by antibody raised against the tumor. Indirect complement consumption assay indicated the presence of Ag-Ab complexes in tumor eluates. It appears that most cell surface immunoglobulin is complexed.

Agglutination Tests↗

Characterization of Fc receptors associated with human malignant tumors.

Fc receptors from human tumors were isolated by sucrose gradient fractionation and affinity chromatography techniques. The isolated Fc receptors showed specificity for IgG(Fc) in the closed chamber hemadsorption technique and also in the inhibition experiments using radiolabeled Fc receptors. The results indicate that Fc receptors isolated from tumor tissue are similar to Fc receptors isolated from normal human spleen, dog macrophages, and peripheral white blood cells (WBCs). However, the Fc receptors isolated from macrophages are more potent inhibitors when compared with tumor, spleen, and peripheral WBC Fc receptors. Also, Fc receptors isolated from the various sources are independent of species specificity.

Antibodies↗

Maturation of monocytes in patients with renal cell carcinoma.

Peripheral blood leukocytes were cultured from patients with renal cell carcinoma and compared with those from normal volunteers. The number of macrophage precursor cells recovered was 17.99 +/- 11.65 X 10(3) cells per ml of blood in patients with renal cell carcinoma, whereas the number recovered in normal individuals was 72.0 +/- 20.0 X 10(3) cells per ml of blood. The low macrophage yield in patients with renal cell carcinoma was not associated with serum factors, and there was no difference in the number of monocytes in the mononuclear cell preparations. Therefore, there seems to be an intrinsic defect in the macrophage maturation process in vitro in patients with renal cell carcinoma.

Adult↗

Deficiency in maturation process of macrophages in human cancer.

Peripheral blood mononuclear cells were cultured from normal individuals and patients with cancer. The analysis of these results indicated a lower number of macrophage precursors (monocytes) in patients with cancer as compared to the number in normal individuals. The macrophage yield was 1.9 +/- 1.1 X 10(4)/ml of blood in patients with cancer versus 7.2 +/- 2.0 X 10(4)/ml of blood in normal individuals. This low yield of macrophages in patients with cancer was not associated with serum factors. Furthermore, a study of the adherent cell population suggests in intrinsic defect in the maturation process in vitro in patients with cancer.

Cell Differentiation↗

Localization of Fc receptors in human and rat malignant tissues.

Three human malignant tumors and a rat carcinoma (Walker 256), which all showed strong Fc receptor activity in tests with sheep erythrocytes (E) sensitized with rabbit IgG antibodies (A), were used to study the distribution of the receptor in subcellular fractions isolated by differential centrifugation. Smears of the three crude sediments obtained (nuclei, mitochondria rich and membrane rich) all possessed receptor activity. EA incubated in the suspension of cell fractions did not attach to Fc receptor positive tissue sections or to cells in suspension. Cells from which the surface receptors had been eluted still showed activity in sections of cell pellets. Apparently the Fc activity is connected with both external and internal membranes.

Adsorption↗

Tumor Fc receptors and tumor-associated immunoglobulins.

Tissue sections and cell suspensions from ten malignant tumors were tested for Fc receptors using sheep erythrocytes sensitized by rabbit IgG antibodies. Surface bound IgG on cells from the same tumors were estimated using an antiglobulin consumption test with 125I labelled human IgG as reference. The amount of IgG present per 10(6) cells varied from less than 100 ng to approximately 600 ng. When these amounts of IgG were plotted against the Fc receptor activity of corresponding tumors, seven of the tumors were distributed along a line showing an inverse linear relationship; i.e. tumors with large amounts of IgG on their cell surfaces had the lowest Fc reactivity and vice versa. Cells from three of the tumors had lower amounts of IgG on their surface than expected from this relationship. However, the lack of correlation could be explained by the focal distribution of the Fc positive tissue within non-reactive tissue. The cells from these areas presumably carry less IgG on their surface and thereby reduce the quantity of IgG calculated per 10(6) cells. Prolonged washing of tumor sections resulted in stronger Fc receptor activity, and correspondingly washed cells had lower amount of IgG on their surface. Presumably the Fc receptor can bind IgG in vivo.

Animals↗

Apparent cellular ingress of albumin in Walker 256 tumor and rat muscle.

Tissue albumin distribution was measured in Walker 256 tumor and skeletal muscle in vivo in 36 rats. Vascular, extravascular-extracellular, and total tissue water spaces were determined for each tissue sample by isotopic techniques. Tissue interstitial and lymph albumin values were calculated from thoracic duct albumin concentrations, and vascular albumin was determined from serum albumin levels. Total tissue albumin was measured by dilution. These data demonstrate a third tissue albumin pool that equilibrates in 3 days compared to the rapid equilibration (2 hr) of vascular and extracellular-extravascular spaces. The pool is present in both muscle and tumor but appears to equilibrate more rapidly in tumor tissue. This finding suggests that cellular ingress of albumin occurs in vivo, which may explain increased albumin catabolism in tumor-bearing hosts.

Albumins↗

Breast conservation therapy with tumor bed irradiation alone in a selected group of patients with stage I breast cancer.

Radiotherapy after breast-conserving surgery increases local control. We tested the feasibility of limited surgery with tumor bed irradiation only with 192Ir in a selected group of patients with stage I breast cancer. Twenty-five breasts in 24 women more than 60 years old with low- or intermediate-grade stage I tumors were treated with placement of interstitial catheters at the time of lumpectomy and axillary node dissection. This procedure was followed by after-loading with low-dose 192Ir to deliver 20-25 Gy to the tumor bed over 24-48 hours. There were neither local recurrences in the breast nor distant recurrences at a median follow-up of 47 months (range 25-90 months). Cosmetic appearance ranged from very good to excellent. There were no long-term complications. It is feasible to treat a select group of patients with tumor bed irradiation, using relatively low doses of interstitial irradiation, with excellent local control and no significant morbidity.

Aged↗