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Biomedical subjects

M Ghoneum

Publications and source records attributed to M Ghoneum.

At least 19 recordsLinked to original sources
PubMed2000

Production of tumor necrosis factor-alpha and interferon-gamma from human peripheral blood lymphocytes by MGN-3, a modified arabinoxylan from rice bran, and its synergy with interleukin-2 in vitro.

Recently, we presented evidence for the role of MGN-3, an enzymatically modified arabinoxylan extracted from rice bran, in potent activation of human natural killer (NK) cell function in vivo and in vitro. In the current study, we examined the mechanism by which MGN-3 elevated NK cytotoxic activity. We did this by testing the action of MGN-3 on the levels of both tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) secretions and MGN-3 function on the expression of key cell surface receptors. Peripheral blood lymphocytes were treated with MGN-3 at concentrations of 0.1 mg/ml and 1 mg/ml, and supernatants were subjected to enzyme-linked immunosorbent assay. Results showed that MGN-3 is a potent TNF-alpha inducer. The effect was dose-dependent. MGN-3 concentration at 0.1 and 1 mg/ml increased TNF-alpha production by 22.8- and 47. 1-fold, respectively. MGN-3 also increased production of IFN-gamma but at lower levels as compared to TNF-alpha With respect to key cell surface receptors, MGN-3 increases the expression of CD69, an early activation antigen at 16 hours after treatment. Furthermore, the interleukin-2 receptor CD25 and the adhesion molecule ICAM-1 (CD54) were upregulated after treatment with MGN-3. Treating highly purified NK cells with MGN-3 also resulted in increased levels of TNF-alpha and IFN-gamma secretion in conjunction with augmentation of NK cell cytotoxic function. Furthermore, addition of MGN-3 to interleukin-2-activated NK cells resulted in a synergistic induction of TNF-alpha and IFN-gamma secretion. Overall, our data suggest that MGN-3, a novel biological response modifier, can be used as a safe alternative or as an adjuvant to the existing immunotherapeutic modalities.

Adolescent↗
PubMed1998

Anti-HIV activity in vitro of MGN-3, an activated arabinoxylane from rice bran.

MGN-3 an arabinoxylane from rice bran that has been enzymatically modified with extract from Hyphomycetes mycelia, was tested for anti-HIV activity in vitro. MGN-3 activity against HIV-1 (SF strain) was examined in primary cultures of peripheral blood mononuclear cells. MGN-3 inhibited HIV-1 replication by: (1) inhibition of HIV-1 p24 antigen production in a dose dependent manner--MGN-3 concentrations of 12.5, 25, 50, and 100 micrograms/ml showed 18.3, 42.8, 59, and 75% reduction in p24 antigen, respectively; and (2) inhibition of syncytia formation maximized (75%) at concentrations of 100 micrograms/ml. Further studies showed that ingestion of MGN-3 at concentration of 15 mg/kg/day resulted in a significant increase in T and B cell mitogen response at 2 months after treatment: 146% for PHA, 140% for Con A, and 136.6% for PWM mitogen. We conclude that MGN-3 possesses potent anti-HIV activity and in the absence of any notable side effects, MGN-3 shows promise as an agent for treating patients with AIDS.

Adjuvants, Immunologic↗
PubMed1997

Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein kinase RNA.

OBJECTIVES: A prominent feature of chronic fatigue syndrome (CFS) is a disordered immune system. Recent evidence indicates that induction of apoptosis might be mediated in a dysregulated immune system by the upregulation of growth inhibitory cytokines. Therefore, the purpose of this study was to evaluate the apoptotic cell population, interferon-alpha (IFN-alpha) and the IFN-induced protein kinase RNA (PKR) gene transcripts in peripheral blood lymphocytes (PBL) of CFS individuals, as compared to healthy controls. SUBJECTS AND METHODS: PBL were isolated from CFS (n = 29) and healthy control individuals (n = 15) and subjected to quantitative analysis of apoptotic cell population and cell cycle progression by flow cytometry. Quantitative competitive polymerase chain reaction (Q/C PCR) and Western blot analysis were used to assess the levels of PKR mRNA and protein in control and CFS individuals. In addition, circulating IFN-alpha was measured by ELISA assay. RESULTS: Increased apoptotic cell population was observed in CFS individuals, as compared to healthy controls (26.6 +/- 12.9% and 9.9 +/- 4.2%, respectively). The increased apoptotic subpopulation in CFS individuals was accompanied by an abnormal cell arrest in the S phase and the G2/M boundary of the cell cycle as compared to the control group (8.6 +/- 1.2 to 22.8 +/- 2.4 and 3.6 +/- 0.82 to 24.3 +/- 3.4, respectively). In addition, CFS individuals exhibited enhanced PKR mRNA and protein levels (mean basal level 3538 +/- 1050 and 2.7 +/- 0.26, respectively) as compared to healthy controls (mean basal level 562 +/- 162 and 0.89 +/- 0.18, respectively). In 50% of the CFS samples (n = 29) treated with 2-aminopurine (2-AP) (a potent inhibitor of PKR) the apoptotic population was reduced by more then 50%. CONCLUSIONS: PKR-mediated apoptosis in CFS individuals may contribute to the pathogenesis and the fatigue symptomatology associated with CFS.

2-Aminopurine↗
PubMed1991

Phorbol myristate acetate corrects impaired NK function of old mice.

Previous studies indicated that natural killer (NK) activity in mice declined with age. In this report, we investigated the basis for the decreased activity of NK cells in older mice. Our results demonstrated that phorbol myristate acetate (PMA)--an activator of protein kinase C (PKC)--corrects the impaired NK function of older animals. The per cent increase of NK activity post treatment with PMA is 226-261% at effector:target (E:T) ratio = 100:1 compared with control untreated cells. The effect of PMA was shown to be dose dependent. A maximum increase in NK activity was achieved at approximately 10-15 nM PMA. Treatment with PMA does not result in increased binding of NK cells to YAC-1 targets as demonstrated by single-cell assay. In addition, treatment of young NK cells with 1-(5-isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride (H-7), a very potent PKC inhibitor, significantly suppressed NK activity (65% of control). Therefore, we conclude that the age-related decline in murine NK activity may reside in the early signalling events leading to triggering of PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Suppression of murine natural killer cell activity by tributyltin: in vivo and in vitro assessment.

The effects of tributyltin chloride (TBTCl) and inorganic tin (IT) on murine natural killer (NK) cell activity were tested in vivo and in vitro. In vivo studies demonstrated that mice fed with TBT (10 and 100 ppm) daily for 1 week exhibited suppression in NK activity 38-46% at effector:target (E:T) ratio = 50:1 compared to control mice. On the other hand, animals treated with inorganic tin showed no change in activity of NK cells. In vitro studies showed leukocytes, preincubated with TBTCl (0.01-0.1 ppm) at room temperature for 1 h and then washed three times, demonstrated significant suppression in NK activity (41 and 85%) at concentrations 0.01 and 0.05 ppm, respectively. Increasing the dose to 0.1 ppm, resulted in complete inhibition of the activity of NK cells. In contrast, IT had no effect on NK activity in vitro at the same concentrations of TBTCl. The effect of TBTCl appears to be due to interference with the binding capacity of effector cells, a necessary prerequisite for target cell lysis. In conclusion, TBTCl proved to be a very potent inhibitor of NK activity; this inhibition may predispose animals to malignancy, which is a characteristic feature reported recently for some TBT compounds.

Animals↗
PubMed1988

Suppression of natural cytotoxic cell activity by social aggressiveness in Tilapia.

Our earlier observations revealed that social stress causes drastic effects on different physiological mechanisms and degenerative changes in leucocytes. In this preliminary work, we analyzed the effect of social aggressiveness on functional activities of leucocytes emphasizing (NCC) activity in Tilapia. At 10 hr post stress induction, fish could be differentiated into three categories: 1) dominants; 2) subordinates; and 3) indeterminants. Results of NCC as indicated by 4 hr. 51Cr-release assay, demonstrated a significant suppression in cytotoxic reactivity in the subordinates and indeterminants compared to dominants. This suppression appears to be due to a decrease in the binding capacity of effector cells to YAC-1 target cells as indicated by the decreased number of conjugate forming cells. This binding process is a key event in activating the fish equivalent of NK cells in mammals. Decreased NCC-activity in stressed fish suggests that aberrations in cell mediated immunity result from social aggressiveness.

Aggression↗
PubMed1988

Phagocytosis of autologous lymphocytes by cervical preneoplastic and neoplastic cells.

Eighty-nine random Pap smears of the uterine cervix were examined to evaluate the phagocytic abnormal cells (PACs) of atypical, dysplastic and neoplastic tissues against infiltrated blood cells. The results revealed that none of the PACs have been identified in atypical (II) and mild dysplastic cells (IIIa). Low levels (1.2%) of PACs were initially demonstrated in patients with moderate dysplasia (IIIb) that increased 1.7-fold in subsequent severe dysplasia (IIIc) and further increased 2.8-fold in invasive carcinomas of the cervix (V). In addition, the data showed age-related responsiveness toward the development of PACs, where 82% of old patients have developed phagocytic activity in moderate dysplastic cells compared with 27% of young patients. However, the difference became less significant at the subsequent classes of the disease. These data further demonstrated that PACs are class-dependent and it may explain one mechanism by which precancerous cells escape immunosurveillance.

Adolescent↗
PubMed1987

Inhibition of SK cell activity in frogs by certain drugs and sugars.

We present similarities between mammalian natural killer (NK) cells and (anuran amphibian) frog spontaneous killer (SK) cells. A cytotoxic assay utilizing allogeneic erythrocytes as target cells was used and lysis assessed by measuring release of hemoglobin. SK effector cells, just as mammalian NK cells, are not sensitive to cycloheximide nor most simple sugars (50 mM glucose, glucose-6-phosphate, galactose, fucose, mannose). However, SK activity is inhibited by chloroquine, colchicine and mannose-6-phosphate. When SK cells were co-incubated with mammalian tumor cells, they were able to lyse only the NK-sensitive target YAC-1, but not other mammalian tumor cell targets including K562, Molt-4, Raji, P815 and EL4. Lysis of YAC-1 cells was also inhibited by colchicine and chloroquine. These results allow speculation on the evolution of cell mediated cytotoxicity since natural cytotoxic cells are present in ectothermic vertebrates.

Animals↗
PubMed1987

Effect of methylcholanthrene on human natural killer cell cytotoxicity and lymphokine production in vitro.

We have developed a simple culture assay system for measuring the in vitro effects of a chemical carcinogen, 3-methylcholanthrene (MCA), on certain activities of human peripheral blood lymphocytes: blastogenesis, cell-mediated cytotoxicity by natural killer cells, interleukin-2 production, lymphotoxin release and percent T-cell subpopulations. After 72 h of treatment with different doses of MCA, blastogenesis was suppressed 23-87% and cell-mediated cytotoxicity was inhibited 45-90%. Interleukin-2 and lymphotoxin production were decreased by 64% and 38%, respectively. On the other hand, MCA treatment at the same doses caused no significant change in the percent of T-cell subsets. We conclude that MCA exerts an inhibitory effect on T-cell functional activity such as interleukin-2 and lymphotoxin production which correlate with a suppression of blastogenesis and natural killer cell activity. This in vitro assay system could be important for future studies in explaining specific inhibitory effects of chemical carcinogens on lymphoid cell function relative to tumorigenesis.

Cytotoxicity, Immunologic↗
PubMed1987

In vivo augmentation of natural killer cell activity by Candida albicans.

We determined in vivo effects of Candida albicans (CA) on murine natural killer (NK) cell activity. C3H mice were treated with heat-killed CA and splenic NK cell activity assayed at 2, 7, 30 and 50 days post treatment. A single injection of CA caused enhancement of splenic NK activity as measured in a 4 h 51Cr-release assay. Peak NK activity was detected at day 7 and persisted for up to 30 days, after which it declined to control values at 50 days. Augmentation of NK activity by CA resulted from enhanced lytic effects of NK cells, which was independent of effector cell binding capacity. Moreover, enhanced NK activity was associated with an increase in the proliferative response to CA antigen and in splenic cellularity when compared to saline injected controls. Thus, CA seems to act as an immunomodulator causing an augmentation of NK cell activity. Since other biological response modifiers (BRMs) do not show the same strength of augmentation, CA could be used as a new BRM having possible anticancer effects.

Adjuvants, Immunologic↗
PubMed1987

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.

Animals↗
PubMed1987

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.

Adolescent↗
PubMed1987

Susceptibility of natural killer cell activity of old rats to stress.

We determined an in vivo response of NK cells in young and old rats towards the suppressive effect of stress. Stress was developed by isolating rats in separate cages, but control littermates were kept together. Animals were subjected to stress for 7 days, and alterations of NK cell activities were examined in the spleen, peripheral blood (PB) and bone marrow (BM). The results showed that old rats subjected to stress had a remarkable decrease in splenic and PB-NK activity compared to old control rats, concomitant with a highly increased level of NK cell activity in BM. Suppression of the lytic activity in the spleen of stressed old rats was correlated with a decrease in the percentage of conjugate formation between splenic NK cells and target tumour cells. In contrast, stressed young rats demonstrated relatively unchanged activity of NK cells examined in different tissues compared to age-matched controls. We concluded that old animals are more sensitive to the suppressive effect of stress compared to young ones, and the mechanism of this suppression is probably due to the migration of large granular lymphocytes (LGL) from spleen and PB to other sites such as BM.

Aging↗
PubMed1987

In situ lymphophagocytosis by nonlymphoreticular neoplasms.

Lymphophagocytosis by nonlymphoreticular neoplasms has been observed. Twenty cancer patients having either adenocarcinoma or epidermoid carcinoma were the subjects of our study. Malignant cells were found to phagocytize autologous lymphocytes, polymorphonuclear cells (PMNs) and red blood cells (RBCs). Papanicolaou smears from cancer patients revealed that 30% (6/20) of the patients had phagocytic malignant cells in situ, the mean phagocytosis for this group was 3.7%. Different cellular elements showed differences in their susceptibility towards phagocytic activity of tumor cells: 2.6% for lymphocytes, 0.7% for PMNs and 0.4% for RBCs. The patients having phagocytic malignant cells showed complete absence of monocytes in their peripheral blood. In contrast, other patients had peripheral blood monocyte percentages within the limits of control values (7.2). However, there was no correlation between development of phagocytic activity of malignant cells and age and sex of patients or type of tumor. This study further confirms that phagocytic activity of nonlymphoreticular neoplasms is a general phenomenon which can be directed against erythroid elements. In addition, we have demonstrated that these tumor cells also phagocytize autologous leukocytes.

Adenocarcinoma↗
PubMed1986

T cell profiles in vitiligo.

The purpose of our investigation was to quantitatively assess T cell profiles in vitiligo and to correlate any aberrations in these findings with the spectrum of clinical disease. Twenty randomly selected vitiligo patients and sixteen healthy matched control subjects were studied. The immunofluorescence and complement-mediated cytotoxicity assays were used to determine the percentages of total T (OKT3), helper (OKT4), and suppressor (OKT8) cells in the peripheral blood of patients and controls. Both assays gave comparable results. Patients with vitiligo had a statistically significant decrease in helper cells and helper/suppressor ratios in comparison with control subjects (p less than 0.01). In addition, there was a statistically significant decrease in helper cells among patients with a disease duration of less than 1 year (p less than 0.01) and in patients who produced serum autoantibodies (p less than 0.05). These findings tend to suggest that aberrations in cell-mediated immunity may be operative in the pathogenesis of vitiligo.

Adolescent↗