Gus Gill

Natural cell-mediated cytotoxicity in vitiligo

Natural cell-mediated cytotoxicity was studied in 18 patients with vitiligo and 13 healthy age-, race-, and sex-matched control subjects. The 4-hour chromium51 (51Cr) release assay was used to determine the activity of natural killer (NK) cells in the peripheral blood against K562 and Molt-4 target cells. Patients with vitiligo had a 50%, 67%, and 60% decrease in the cytotoxic response with Molt-4 cells at effector-target ratios of 25:1, 50:1, and 100:1, respectively, in comparison with control subjects (p less than 0.001). This inhibition was consistent with an 80% decrease in the binding capacity of NK cells to Molt-4 target cells (p less than 0.005). In contrast, cytotoxic responses did not differ in patients and control subjects with K562 target cells. These results suggest that patients with vitiligo have a decreased capacity for effector cell recognition of Molt-4 target cells but not K562 target cells. Hence patients with vitiligo may have defective clones of NK cells that are incapable of initial recognition of Molt-4 target cells, a necessary prerequisite for target cell lysis. Perhaps this phenomenon occurs with other tumor cells, which would explain the association of vitiligo with certain internal malignancies.

Suppression of basal and Corynebacterium parvum-augmented NK activity during chemically induced tumor development.

C3H mice were injected subcutaneously (s.c.) with a tumorigenic dose (150 micrograms/mouse) of 3-methylcholanthrene (MC), followed by a 24-h injection and subsequent weekly injections of Corynebacterium parvum (CP) i.p. for a total of 100 days. Basal and CP-augmented NK cell activities were measured in controls and treatment groups during pre-tumor and tumor development stages. Basal NK activity in spleen, peripheral blood and lung tissue was enhanced by CP, but was suppressed by MC. A resulting transient MC induced suppression of splenic NK activity at 10 days was partially restored and sustained by CP treatment and immunosuppression was again observed in tumor-bearing compared to control mice. Mice treated with MC alone showed a higher tumor incidence than animals treated with MC + CP at 45-60 days, while there was no difference in tumor incidence in these two treatment groups at 100 days post injection. The mechanism of the observed transient immunosuppression induced by MC appears to be related to an early toxic effect on large granular lymphocytes (LGL) which was decreased at 10 days and again at 100 days in tumor-bearing mice. Although MC did not appear to exert an effect on effector:target cell conjugate formation, an early suppression in the lytic activity of LGL, may have predisposed the animal to malignant transformation of susceptible cells at the site of MC injection.

Phagocytosis of candida albicans by lymphatic tumour cells in vitro

Experiments were carried out to investigate whether different lymphatic tumour cell lines have similar kinetic characteristics of phagocytosis of microorganisms. Six tumour cell lines were used. These were a human T-cell line (CEM), a mouse T-cell line (YAC-1), a human B-cell line (LAZ), and a human erythroleukemic tumour cells (K562), whereas 2 cell lines of professional phagocytosis were used as controls, a human macrophage cell line (THP1) and a mouse macrophage cell line (P388D1). Tumour cells were mixed with candida albicans at a ratio of 10:1 of candida to tumour cells and the percentage of tumour cells that had attached/phagocytosed candida was determined. After 4 h coculture with candida, tumour cells not of T-cell origin (LAZ and K562) showed moderate level of phagocytosis (28%), whereas tumour cells of T-cell origin (CEM and YAC-1) demonstrated low levels of phagocytosis (15%) as compared to macrophage cell lines (THP1 and P388D1) that showed maximum phagocytosis (64-78%). Acid phosphatase (AcPase) activity was increased by 33% during coculture of YAC-1 cells and yeast cells. In conclusion, the results suggest that lymphatic tumour cells of nonphagocytic origin acquire phagocytic properties during the course of malignancy, and digestion of phagocytosed yeast cells maybe related with AcPase activity, as well as that of other lysosomal enzymes. This phenomenon may represent one mechanism by which tumour cells downregulate immune surveillance.

Potential biomarkers for head and neck squamous cell carcinoma.

Objective The purpose of the study was twofold: 1) to search for potential biomarkers that were overexpressed in cell lines that could represent both a clinical premalignant (immortalized) and a malignant state, and 2) to attempt to correlate metallothionein gene expression with clinical outcome in laryngeal carcinoma.

Computed tomography of palatine tonsillar carcinoma

Twenty-five patients with surgically and histologically proven squamous cell carcinoma of the palatine tonsil were studied with computed tomography (CT) using a high dose intravenous contrast enhancement technique. With this technique, CT demonstrated the primary carcinoma within the palatine fossa as well as its contiguous spread to the base of the tongue, mobile tongue, lateral pharyngeal wall, supraglottic larynx, and nasopharynx and metastasis to local deep cervical lymph nodes.

Murine Inter-Sex Difference in Methylcholanthrene Induced Tumor and its Correlation with NK Activity

Susceptibility to 3-methylcholanthrene (MC) induced tumor development between adult male and female C3H mice at 3–4 mo. old was examined. Animals that were injected (s.c.) with a tumorigenic dose (150 μg/mouse) of MC demonstrated a significant difference in the latent period of tumor development between both sexes. Female mice were more responsive and developed tumors at 3 wks after treatment, whereas, male mice were less responsive as indicated by the longer latent period (10 wks). In order to correlate these data with activity of natural killer (NK) cells, splenic NK activity was measured by 4 hr 51Cr-release assay. The results showed male mice having higher activity: 27 lytic units (LU) in comparison to female ones (3 LU). This was attributed to a decrease in the lytic effect of female NK cells (11%) compared to male mice (20%), since the binding capacity of effector cells to their targets was similar in both sexes (15%), as indicated by single cell assay. The possible role of an immunosuppressive factor (IF) in the sera of female mice was investigated. NK cells from young females demonstrated 33% suppression in activity post culture with sera from 3–4 mo. old female mice. In conclusion, this study demonstrates a sex-linked tumor development by MC treatment, and correlates this phenomenon with differences of NK activity between young male and female mice as well as in the age-dependent decline of reactivity. A possible immunosuppressive mechanism may be operative in explaining as to why MC is more effective in tumorigenesis in female mice as opposed to males.

The Effects of Carcinogenic Methylcholanthrene on Carbohydrate Residues of Nk Cells

The present study examines the effect of methylcholanthrene (MCA), a carcinogenic polycylic hydrocarbon, on the carbohydrate receptor determinants (RD) on natural killer (NK) cell surface using the bead-coupled lectin assay. Murine NK cells exhibited different degrees of preferential binding to the specific lectins tested. Of the ten lectins tested, five exhibited a positive binding affinity while the remaining five exhibited no or insignificant binding. NK cells bind to beads derivatized with mannose specific lectins: Concanavalin A (Con A), Lens culinaris, and Pisum sativum. NK cells also bind to other lectin beads such as Triticum vulgaris (GalNac) and Vicia villosa (D-G1cNAc). All these lectin beads exhibited greater than 90% adhesion. The underivatized control beads exhibited no NK binding. The NK cells that were exposed to MCA for 2 h demonstrated a significant decrease in lectin bead-cell coupling in a dose dependent manner. MCA (10μg/mL) caused a 17.8%, 40% and 4.7% decrease in binding affinity when introduced to the mannose specific lectins; Con A, L. culinaris and P. sativum beads, respectively. The binding of T. vulgaris and V. villosa to NK cells was inhibited (23.4% and 28%) by MCA treatment. An increase in the dose to 20μg/mL resulted in a greater inhibition in binding affinity towards lectin beads, Con A, 35.3%, L. culinaris, 62.6%, P. sativum, 30.9%, T. vulgaris, 44.2% and V. villosa, 46.2%. The effect of MCA on the synthesis of NK polyphosphoinositides such as phosphatidylinositol 4-phosphate (PIP), phosphotidylinositol 4, 5- biphosphate (PIP2) was examined. The results showed lower phosphate 32 (32P)-labeling of PIP and PIP2 of MCA-treated NK cells as compared to untreated cells. Both of these MCA-induced cellular events (carbohydrate RD, PIP, and PIP2) may be interrelated at the level of transmembrane signal transduction, and may represent important steps in the inhibition of NK mediated cytotoxicity by this carcinogen.