PubMed Health⌕ Search

Biomedical subjects

J Gabrilovac

Publications and source records attributed to J Gabrilovac.

At least 19 recordsLinked to original sources
PubMed2006

PMA and doxorubicin decrease viability, MTT activity and expression of CD10 marker on NALM-1 leukemic cells.

PMA (10, 20 ng/ml) and doxorubicin (5-20 ng/ml) decreased the viability and MTT-activity of NALM-1 pre-B leukemic cells (3 days' treatment). Further, CD10 was downregulated, suggesting that PMA and doxorubicin induced differentiation of NALM-1 cells. However, PMA did not alter expression of B cell markers CD20 and of mIgM. In contrast to PMA, another differentiation agent ATRA did not alter CD10 expression on NALM-1 cells but affected viability after 6 days (5, 10 ng/ml). The data in this study are the first evidence that PMA and doxorubicin inhibited viability and MTT activity and induced partial differentiation, by decreasing CD10 on NALM-1 cells.

Antibiotics, Antineoplastic↗
PubMed2004

A pilot study of mitochondrial DNA point mutation A3243G in a sample of Croatian patients having type 2 diabetes mellitus associated with maternal inheritance.

In this work, patients having type 2 diabetes mellitus and diabetic mothers were tested for the presence of mitochondrial DNA point mutation A3243G. This mutation is associated with the MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), diabetes and deafness. Twenty-two diabetic persons were screened. DNA was isolated from peripheral blood lymphocytes and from swabs of oral mucosa. The mitochondrial DNA point mutation A3243G was detected using PCR-RFLP test. The mutation was detected in oral mucosal DNA of two patients (but not from lymphocyte DNA). One patient was a man with hearing and visual impairments and proteinuria; the other was a woman having proteinuria but no hearing impairment. The mutation was not detectable in oral mucosal DNA from the control persons: 20 diabetic patients having diabetic fathers and 22 healthy, nondiabetic volunteers. The incidence of mitochondrial DNA point mutation A3243G in this study of Croatian diabetic patients is in line with data in the literature.

Adenine↗
PubMed2000

Gender-related differences in murine T- and B-lymphocyte proliferative ability in response to in vivo [Met(5)]enkephalin administration.

Gender-related differences in response to drugs of abuse, such as cocaine and morphine, have been reported both in humans and in experimental animals. Besides causing analgesia, morphine has recently been shown to exert strong immunosuppressive activity. However, no data on the influence of gender on the immunomodulatory effects of morphine or opioid peptides have been reported yet. The aim of this study was to test the influence of gender on the immunomodulatory ability of the endogenous opioid peptide [Met(5)]enkephalin (MENK) in mice. This was done by comparing the proliferative ability of splenic T- and B-lymphocytes 14 h after systemic (intraperitoneal; i.p.) administration of [Met(5)]enkephalin (2.5, 5 or 10 mg/kg body weight). The proliferative ability of T- and B-lymphocytes was assessed by testing their in vitro response to graded concentrations of the T- and B-cell mitogens, concanavalin-A (Con-A) and lipopolysaccharide (LPS), respectively. The results obtained showed that [Met(5)]enkephalin, at a dose of 2.5 mg/kg, enhanced the proliferative ability of T-lymphocytes in male mice, but not in female mice. Similarly, [Met(5)]enkephalin, at doses of 2.5 and 5 mg/kg, enhanced the proliferative ability of splenic B-lymphocytes in male mice, whereas in female mice a decrease was observed ([Met(5)]enkephalin 2.5 mg/kg, LPS 10 microg/ml). [Met(5)]enkephalin, at a dose of 10 mg/kg, did not affect the proliferative ability of either lymphocyte population, regardless of gender. The [Met(5)]enkephalin-induced stimulatory effect on both T- and B-lymphocyte proliferation was reversed by naloxone (10 mg/kg body weight), injected prior to [Met(5)]enkephalin, suggesting an involvement of opioid receptors. Thus, the data presented provide evidence for the gender-related response of murine splenic lymphocytes to immunomodulation by [Met(5)]enkephalin, administered in vivo. This finding may be relevant to the potential use of [Met(5)]enkephalin in adjuvant therapy for immunocompromised states, such as acquired immunodeficiency syndrome (AIDS) or malignancies.

Animals↗
PubMed1997

Enkephalins in hematopoiesis.

Recent data support the view that neuropeptide mediators, in particular opioid peptides, participate in the control of hematopoiesis. The main arguments are: neuropeptides modulate the functions of lymphoid cells, macrophages and mature granulocytes; they control cell proliferation and differentiation in many tissues, particularly during embryogenesis; lymphoid cells, macrophages, polymorphonuclear granulocytes and bone marrow stromal elements express neuropeptide receptors; bone marrow cells produce opioid-like neuropeptides; the CD10/CALLA marker of lymphoid, myeloid and marrow stromal cells is an enzyme, endopeptidase, which cleaves- and thus activates/inactivates-opioid and other neuropeptides. We have shown that opioid peptides enkephalins, opioid antagonist naloxone, and the inhibitor of enkephalin-degrading endopeptidase, thiorphan, modulate the proliferation and differentiation of hematopoietic cells in clonal and long-term cultures of mouse bone marrow. The effects partly depended on the presence of the accessory hematopoietic elements, and followed a circadian pattern. The dose-responses were irregular, showed strain-dependent and individual variations, and apparently reflected the state of the activity of target cells, cellular interactions and simultaneous signals by other mediators. The enkephalins were shown to bind to specific (opioid) receptors on the target cells, and their signals to be transmitted to the cell interior by a cascade of secondary messengers including diacyl-glycerol (DAG), protein-kinase C (PKC) and Ca++ ions. Neuropeptide regulation of hematopoiesis might belong to a complex immuno-neuroendocrine network including melatonin.

Animals↗
PubMed1996

Leu-enkephalin enhances interferon secretion in mice.

This work has explored the possibility that alterations of NK activity induced by the opioid pentapeptide leu-enkephalin (LENK) may reflect the alterations in secretion of IFN, an important regulator of NK activity. The NK activity in the spleen of mice was determined in parallel with the plasma IFN level 24 and 48 h after an i.p. injection of LENK (10 mg/kg). A known inducer of IFN secretion, polyinosinic-polycytidylic acid (poly-IC), was also used. LENK injection significantly increased basal IFN secretion 24 and 48 h later. The level was comparable to that induced by poly-IC. However, LENK was not able to augment the poly-IC-increased IFN level. The increase of IFN at 48 h coincided with a mild enhancement of NK activity in the spleens, but 24 h after LENK injection, the increased IFN level in plasma was associated with a significant drop of splenic NK activity. LENK did not affect the NK activity stimulated with poly-IC. Naloxone (20 mg/kg), an opioid receptor-blocking agent, only partly diminished the LENK-induced IFN secretion. However, naloxone itself increased the plasma IFN level. These data indicate that the immunomodulatory effects of the opioid peptide LENK in vivo are associated with alterations of IFN secretion.

Animals↗
PubMed1996

Met-enkephalin modulates stress-induced alterations of the immune response in mice.

Overnight restraint stress of mice decreased ConA-driven lymphocyte proliferation, plaque-forming cell response to sheep red blood cells (SRBC), and NK activity in the spleen, but the phagocytic activity was enhanced. Injection of methionine-enkephalin (MENK), 10 mg/kg, i.p., 30 min before restraint, abolished these changes (except for the NK activity) and attenuated the stress-induced elevation of glucocorticoids. However, MENK itself affected the immune responses like stress: It decreased NK activity and the PFC response and enhanced phagocytic activity. Contrary to results with stress, MENK had no effect on cell proliferation. The opioid-receptor antagonist naloxone given before restraint reversed the stress-induced enhancement of phagocytosis and the decrease of T-cell proliferation. Alterations of the immune responses induced by restraint stress seem to be mediated by at least two mechanisms: activation of the hypothalamus-pituitary-adrenal (HPA) axis and the secretion of opioid peptides. MENK injected before stress may interfere with either or both mechanisms. T or B lymphocytes seem to be affected by the activation of the HPA axis, and phagocytes by a direct opioid action, whereas NK cells seem to be under the influence of another control mechanism.

Animals↗
PubMed1996

Pretreatment of human peripheral blood lymphocytes with interleukin-2 or dexamethasone does not alter their response to Met-Enkephalin in a NK-cytotoxic assay.

The effect of Met-Enkephalin (MENK; 10(-12) - 10(-8) M) on NK-activity of peripheral blood lymphocytes (PBL) after in vitro treatment (18 h, 37 degrees C) was examined in 30 young, healthy male donors. In the group as a whole (n = 30), no significant effect of MENK was detected. At the individual level, 18 of 30 donors (60%) responded to MENK either by mild enhancement (up to 8%, 8 responders), or by mild attenuation (up to 12%, 10 responders) of the basal NK-activity. The effect of MENK was donor-related regarding the dose-response, E/T ratio, and direction of MENK action. The influence of pretreatment of PBL (1 h) with either graded doses of interleukin-2 (IL-2; 3, 25, 50 U/ml) or dexamethasone (Dex; 2.5 x 10(-9), 2.5 x 10(-8), 2.5 x 10(-7) M), on the effect of MENK was also tested. The idea was that pretreatment of PBL would result in predictable, and/or stronger response to MENK. In the group as a whole again no significant effect of MENK was detected on the NK-activity of PBL prestimulated by IL-2 (n = 16), or inhibited by Dex (n = 12). Further, pretreatment of PBL with IL-2/Dex did not significantly alter the intensity of modulation by MENK, which was generally mild. The data obtained have shown that pretreatment of PBL with IL-2 or Dex, regardless of their concentrations, did not significantly alter the frequency of responders to MENK being 50%, 62.5% and 64.3% with 3, 25 or 50 U/ml IL-2, respectively, and 50% with all concentration of Dex used, as compared to that observed with resting PBL (60%). However, at the individual level physiological concentrations of MENK (10(-12) - 10(-9) M) induced enhancement or/and attenuation of the NK-activity pretreated with IL-2/Dex, respectively. The effect of MENK at the individual level was donor-related regarding the dose-response, E/T ratio, and direction of MENK action. Thus, pretreatment of PBL with graded concentrations of IL-2/Dex did not alter the effect of MENK on NK-activity, regarding the frequency and intensity, as well as the direction of modulation: it remained bidirectional, of low intensity, and independent of the grade of PBL preactivation/inhibition, therefore unpredictable.

Adolescent↗
PubMed1993

A characterization of the in vivo immunomodulation by Met-enkephalin in mice.

Single intraperitoneal injections of Met-enkephalin (MENK) into CBA mice decreased the phagocytic activity of peritoneal macrophages, Con-A-induced proliferation and NK-activity of spleen cells. Conversely, in mice which had been immunized with sheep erythrocytes, treatment with MENK was associated with enhancement of phagocytosis, and no effect on lymphoid proliferation and NK-cytotoxicity of spleen cells. MENK-induced inhibition of cellular functions in nonimmunized mice was associated with a decrease of plasma ACTH level, whereas MENK-induced stimulation of phagocytosis in immunized mice was paralleled with an elevation of ACTH, suggesting a role of corticoids in immunomodulation by MENK. MENK-induced modulation (suppression and stimulation) of phagocytosis, as well as inhibition of spleen cell proliferation, was not observable in adrenalectomized mice, although a reduced NK-cytotoxicity was still present.

Adrenal Glands↗
PubMed1993

Leu-enkephalin modulates the migration inhibition of mouse splenocytes induced by cAMP-elevating agents.

The ability of Leu-enkephalin (LENK) to alter random migration of mouse spleen cells was tested in vitro and in vivo. Incubation of the cells with LENK (10(-14) M-10(-7) M) for 1 h at 37 degrees C suppressed the migration. The dose-response was irregular, showing two peaks in the physiological concentration range: 10(-10) M, and 10(-13)-10(-14) M. Intraperitoneal (i.p.) injection of LENK (7.5 mg/kg body wt) depressed the migratory capacity of the splenocytes harvested 2 and 24 h later. In contrast to the inhibitory effect of LENK on the migration of native cells, its effect on cells pretreated with the cAMP-elevating agents theophylline, 3-isobutyl-1-methyl-xanthine (IBMX) and forskolin was predominantly a stimulatory one. The addition of LENK resulted in attenuation or even full reversion of the migration-inhibition caused by those agents. Occasionally, potentiation of the suppression was also observed. There was no discrimination between the phosphodiesterase (PDE) inhibitors IBMX and theophylline, and the adenylate cyclase activator forskolin. Specificity of LENK effects was tested by using naloxone (10(-6) M), an opioid-receptor antagonist. Migration-inhibition induced by LENK was reversed in about two-thirds of the experiments. In contrast, migration-inhibition induced by cAMP-elevating agents, could not be reversed by naloxone. Naloxone itself was not inert, usually suppressing the locomotor ability of splenocytes. The data suggest that LENK-induced modulation of cell migration is (at least partly) mediated via opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1992

Regulation of NK cell activity and the level of the intracellular cAMP in human peripheral blood lymphocytes by Met-enkephalin.

The effect of Met-enkephalin on natural killer (NK) activity and on intracellular cyclic adenosine monophosphate (cAMP) level in human peripheral blood lymphocytes was measured 1/4, 1, 2, and 24 h after incubation. Concentrations of Met-enkephalin ranged from 10(-12) to 10(-8) M. Cyclic changes in NK activity and in the intracellular cAMP level after treatment with Met-enkephalin were observed. Kinetics of changes caused by high (10(-9), 10(-8) M) and low concentrations (10(-12), 10(-11), 10(-10) M) of Met-enkephalin differed from each other. Early, nearly threefold increase in the level of intracellular cAMP was found 15 min after treating peripheral blood lymphocytes with 10(-12) M Met-enkephalin. By contrast, a nearly 75% decrease of intracellular cAMP level was found 2 h after treatment with 10(-9) M Met-enkephalin. Generally, early intensive changes in the cAMP level in peripheral blood lymphocytes, induced by Met-enkephalin, were followed by delayed, subtle changes in NK cell activity in the opposite direction.

Adolescent↗
PubMed1992

In vivo bidirectional regulation of mouse natural killer (NK) cell cytotoxic activities by Leu-enkephalin: reversibility by naloxone.

Intraperitoneal injection of Leu-enkephalin (LENK, 10 or 7.5 mg/kg) induced bidirectional modulation of natural cytotoxic activities in spleens of CBA mice (suppression followed by enhancement). NK-cytotoxic activity was more affected than the ADCC. Early suppression of NK activity could be reversed by 4 x M excess of naloxone injected 20 min before LENK, suggesting that the suppression was mediated by opioid receptors. Subsequent increase of NK activity could not be abrogated by naloxone, at least not completely. Naloxone itself decreased NK activity 12 hours after treatment, but enhanced ADCC at 24 and 48 hours. This increase was abrogated by LENK. In addition to functional alterations, LENK also induced phenotypic changes of spleen cells, i.e. a decrease in the percentage of asialo-GM-1+ cells 24 hours posttreatment. There was no correlation between LENK-induced alterations of cytotoxic function and the percentage of cells with NK phenotype (GM-1+). Thus, LENK modulates cytolytic functions and the phenotype of NK cells in vivo in a complex way, which besides opioid mechanisms may also include non-opioid ones.

Animals↗
PubMed1992

Alteration of NK- and ADCC-activities in rats genetically selected for low or high platelet serotonin level.

By selective breeding we have recently obtained two discrete sublines of rats that differ in serotonin content in their platelets. As both serotonin and platelets may influence, or even take part, in immune reactions, we tested in this work the natural cytotoxicity in rats with constitutionally different platelet serotonin levels (PSL). Rats with low platelet serotonin level (mean +/- SD, 1.26 +/- 0.14 micrograms 5HT/mg protein; 81% vs. controls) had significantly higher (P less than 0.001) natural killer (NK) activity (mean +/- SD, 9.1 +/- 3.9%) than control rats with average PSL (1.57 +/- 0.18 micrograms 5HT/mg protein). On the contrary, rats with constitutionally high PSL (2.42 +/- 0.21 micrograms 5HT/mg protein, 154% vs. controls) had somewhat lower (P less than 0.02) NK activity (4.1 +/- 1.7%) than control animals (5.7 +/- 1.9%). Antibody-dependent cellular cytotoxicity (ADCC) against nucleated targets of the RCH line, detecting lymphoid effectors, as well as ADCC against chicken red blood cells (CRBC), detecting predominantly non-lymphoid effectors, were also significantly higher (P less than 0.001) in rats with low PSL (19.6 +/- 6.8% vs. 6.6 +/- 3.1% in controls for lymphoid effectors, and 71.8 +/- 6.1% vs. 48.7 +/- 8.8% in control rats for non-lymphoid effectors). However, no significant alteration of either ADCC was determined in rats with high PSL. The results suggest in vivo regulation of natural cytotoxicity by serotonin.

Animals↗
PubMed1992

Interaction of Met-enkephalin and corticosteroids in immunomodulation.

The effect of Met-enkephalin (MENK) on several immune functions, corticosterone (CS) and adrenocorticotropin (ACTH) levels in the plasma was studied in adrenalectomized (ADX) and sham-adrenalectomized (SADX) mice. Multiple Met-enkephalin injections (10 mg/kg per day in two injections 12 h apart, for 4 days) increased the plaque-forming cell response to sheep erythrocytes in the spleen and enhanced the proliferation of spleen cells in vitro. These effects were comparable in sham-adrenalectomized and adrenalectomized mice. However, spleen cells of mice immunized with sheep red blood cells and injected with Met-enkephalin, showed suppressed blastogeneic transformation with Con A. The effect was equal in adrenalectomized and sham-adrenalectomized mice. In the absence of Con A in spleen cell cultures, MENK treatment of donor mice resulted in a significant mitogenic effect. NK activity of the spleen cells was suppressed in MENK-treated adrenalectomized mice. Injection of MENK decreased corticosterone levels and increased ACTH levels in the plasma of sham-adrenalectomized mice. In adrenalectomized mice plasma levels of ACTH were decreased by MENK. It seems that corticosteroid secretion, although changed by adrenalectomy and influenced by treatment with MENK, does not influence the modulatory effect of MENK on the PFC response and blastogeneic transformation of mouse spleen cells. However, NK activity of the spleen cells treated with MENK seems to the reflect joint action of MENK and corticosteroids.

Adrenalectomy↗
PubMed1990

Opposing influence of age on the growth and colony-forming ability of mouse melanoma B16 and mammary adenocarcinoma: correlation with natural killer activity.

C57B1 and CBA mice of different ages (6, 12, 26 or 35 weeks) received intramuscular inocula of melanoma B16 or mammary adenocarcinoma (MCa), respectively. Median survival time was shorter, the younger the recipients. Tumor enlargement was correspondingly retarded in older mice. This was associated with decrease of natural killer (NK) activity in the spleens. However, the cytotoxicity against fresh syngeneic tumor cells, increased with age in CBA mice. In contrast to the growth of intramuscular tumors, the ability of intravenously injected B16 or MCa cells to form nodules in the lungs was significantly superior in old animals (35 weeks or more), with low levels of NK activity, than in young ones (6 weeks) with high levels of NK activity. Stimulation of NK activity by poly(I).poly(C) reduced the number of MCa colonies by 50% in the lungs of old mice, but had no effect on colony-forming ability in young animals. The observed association of tumor growth with age and NK activity levels may reflect (a) an interplay of tumor-inhibiting and tumor-promoting effects of NK cells, changing with age, and (b) the accessibility of tumor cells, inoculated intramuscularly or captured in the lungs, to these influences.

Adenocarcinoma↗
PubMed1990

Immune response of stressed rats treated with drugs affecting serotoninergic and adrenergic transmission.

Stressful conditions interfere with immune response. One of the principal mechanisms is activation of hypothalamo-pituitary-suprarenal axis by central serotoninergic and adrenergic pathways. Alternative mechanisms bypassing the axis also take part in stress-induced immunomodulation. Immunosuppression caused by repeated restraints or over-crowding was usually accompanied by increased metabolism of serotonin in the brain (as indicated by increased level of its metabolite, 5-HIAA) and by increased levels of corticosterone in plasma. Changes in lymphatic tissues of stressed animals that result in suppression of immune response apparently "outlive" fluctuating changes in neurotransmitter and corticosterone levels. Drugs that alter serotoninergic or adrenergic transmission interfere with immunosuppressive effect of stress either synergistically (augmenting suppression) or antagonistically (preventing it). Since immunocompetent cells possess serotoninergic and adrenergic receptors, such drugs may exert their effect either via central neuroendocrine mechanisms, or by direct effects on immunocompetent cells.

Animals↗
PubMed1989

In vivo and in vitro modulation of NK and ADCC activities of mouse spleen cells by peptidoglycan monomer (PGM).

The ability of peptidoglycan monomer (PGM), an immunomodulator obtained from Brevibacterium divaricatum, to modulate NK and ADCC activities of spleen cells was tested in mice with constitutively weak (C57B1) or strong NK activity (CBA, C3H). In weak reactors, i.v. injection of PGM enhanced the NK and ADCC activity as effectively as a known stimulator, poly I.C, and the dynamics of the response was comparable. In strong reactors, PGM caused two peaks of the ADCC response, and one peak of NK stimulation (after an initial decline), whereas poly I.C caused more or less persistent stimulation of both activities. Incubation of spleen cells with PGM was generally less effective than the treatment in vivo. No alteration of NK activity was recorded at high effector-to-target ratio (E:T), and at low ones, PGM caused suppression. This was true both for weakly and strongly reactive cells. ADCC was either unchanged (CBA spleen cells), stimulated (C3H), or suppressed at high E:T and enhanced at low E:T (C57B1). PGM apparently activates an interlocked regulatory mechanism, and the final outcome probably depends on relative concentrations of regulatory and effector cells and on their per cell activities. Hence the effect varied with the time interval between treatment and assay, with strain-related constitutive reactivity, and with the E:T ratio.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Defect of NK activity in children with untreated acute lymphocytic leukemia (ALL). I. Dependence on the blast count and phenotype, and response to exogenous and endogenous alpha-interferon.

Endogenous NK-activity (eNK) against K-562 cells was determined in peripheral blood of 68 children with acute lymphocytic leukemia (ALL) before treatment. In 53% of them it was depressed, and in 47% it was within the range of control children (27) and adults (104). There was a significant negative correlation between blast contamination of peripheral blood and the level of eNK-activity. In spite of this general trend, 8 patients with high blast count have had normal eNK-activity, and 10 patients with relatively low blast count (below 50%) have had depressed eNK-activity. Examples of T ALL showed significantly lower eNK-activity than CALLA ALL. The ability of exogenous alpha-interferon (IFN) to stimulate eNK-activity was impaired in 18 of 40 examples of ALL and preserved in 22. The IFN-induced NK-response was also negatively correlated to the blast burden, but again with exceptions: Six nonresponders in spite of low blast count, and six responders in spite of high blast count in peripheral blood. IFN-inducer, poly-IC, stimulated eNK-activity only in 6 of 26 ALL samples. Surprisingly, positive correlation was found between poly-IC-induced NK-stimulation and blast count in peripheral blood. Poly-IC induced significant IFN production only in one of six cultures of ALL. Impaired eNK-activity has been attributed, in part, to "dilution" of NK cells by the blasts. Defects in production of IFN, and in response to it, may be additional reasons for depressed NK-activity in about 50% of children with untreated ALL.

Adolescent↗