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Biomedical subjects

M Dorić

Publications and source records attributed to M Dorić.

15 recordsLinked to original sources

Plasma cytokine response in mice with bacterial infection.

BACKGROUND: Exposure to microorganisms elicts the production of cytokines. These soluble factors enhance several innate immune functions and regulate the ensuing specific immune response aimed at limiting the spread of infection. AIM: This study was undertaken to quantify the plasma levels of pro-inflammatory cytokines during the course of primary Listeria monocytogenes and Campylobacter jejuni infection. Using an in vivo infection the relationship between endogenous cytokines and the bacterial number in the liver of infected animals was examined. METHODS: C57BL/6 mice were infected by the intraperitoneal route. At different time points we determined the number of colony-forming units of bacteria in the liver of infected animals and paralled these with the plasma levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) measured by enzyme immunoassays. RESULTS: L. monocytogenes infection lasted 10-11 days. IFN-gamma production occurred in the early phase but was more pronounced after day 4, following the appearance of specific immunity. The duration of experimental campylobacteriosis was 15 days. Early IFN-gamma production was not significant but a progressive rise of this cytokine in plasma was seen during the second week post infection. Mice produced measurable amounts of plasma TNF-alpha immediately after being given viable L. monocytogenes, peaking on day 2-3 when the greatest number of bacteria was present in the examined organs. During C. jejuni infection plasma TNF-alpha was produced in a similar manner, but the highest concentrations were found a few days later than in listeriosis, in correlation with the different course of campylobacteriosis. The quantity of IL-6 increased and decreased in concordance with clearance of L monocytogenes and the clinical status of the animals. C. jejuni did not promote the induction of this cytokine. This is to some extent an unusual finding. With respect to the role of IL-6 in Th2 responses and antibody production, the appearance of this cytokine in campylobacteriosis was more expected. DISCUSSION: During systemic bacterial infection, a network of pro-inflammatory cytokines is activated and blood levels of these cytokines are elevated, albeit inconsistently, with large individual variations and depending on microbial characteristics and structure.

Animals↗

Primary Campylobacter jejuni infection in different mice strains.

Campylobacter jejuni is one of the most frequent causes of diarrhoea in man. Extra-intestinal manifestations may also occur, particularly in immunocompromised individuals. However, because of the lack of appropriate animal models the pathophysiology and immunological response of the host to C. jejuni infection are still poorly understood. In our laboratory an experimental infection of adult BALB/c, C57BL/6 and DBA/2 mice has been established. After intraperitoneal injection of 0.5-1x10(9) cfu of C. jejuni none of the infected mice showed clinical symptoms of illness, but bacterial spreading and tissue invasion were achieved. We have concentrated our studies on the duration of primary infection, recovery of bacteria from livers and spleens of infected animals and pathohistological changes of these organs. Our results showed differences in the course of systemic infection among the tested mice strains. BALB/c mice were most sensitive, resulting in the most pronounced pathohistological changes in the examined organs. The duration of the primary liver infection was the longest in BALB/c mice while the duration of the splenic infection also differed among the tested mice strains. Nevertheless, the experimental model used in this study can be efficiently used in further analysis of the pathogenesis of this bacterial infection. However, the strain differences should be taken into account depending on the parameters to be followed.

Animals↗

Primary Listeria monocytogenes infection in gestating mice.

The facultative intracellular Gram-positive bacterium Listeria monocytogenes is a food-borne pathogen of frequently underestimated importance. Pregnant women represent the high-risk group for L. monocytogenes infection. Abortion, stillbirth or neonatal infection can be the serious outcome of such an infection. Recovery from listeriosis, resistance mechanisms of the host and the effect of L. monocytogenes on fetal development still remain to be fully understood. The results of our experiments showed an increased susceptibility of gestating BALB/c mice to primary L. monocytogenes infection. The duration of listeriosis in gestating animals was almost twice longer than in the control group. Furthermore, it was clearly shown that the detrimental effect of L. monocytogenes on fetal development was more pronounced if the infection was acquired earlier during gestation.

Animals↗

Changes in macrophage function during chemotherapy.

Antibiotics, in addition to killing or inhibiting the growth of microorganisms, may also affect the mechanism of host defence in many ways. Such effects may be clinically relevant especially in the case where an impairment of immunological function can be seen. We, therefore, decided to study the influence of penicillin G, cefotaxim, ceftazidime, streptomycin, and lincomycin on the function of phagocytes by using the macrophage adherence assay and the macrophage spreading assay. We also followed the concentrations of neopterin and interferon gamma (IFN gamma) in the plasma of mice treated with the above mentioned antibiotics. Changes in adherence of peritoneal macrophages were seen in mice treated with therapeutic doses of penicillin G and cefotaxim, after 2 h of incubation. Cefotaxim and streptomycin in the usual therapeutic dose and ceftazidime in a fourfold higher dose influenced the capacity of peritoneal macrophages to spread on a glass surface. The same was seen with lincomycin when administered in the therapeutic dose and in a fourfold higher dose. In all the mice treated with antibiotics the concentration of IFN gamma was higher than in the control mice, while the reverse was seen concerning neopterin release, with an exception in mice treated with streptomycin.

Animals↗

[Acute hemorrhagic ulcer in a 3-month-old child].

A case of the acute haemorrhaging ulcus in a three-months old infant with lethal outcome is presented in this paper. The unclear proximal gastrointestinal haemorrhage didn't indicate the possibility of the presence of ulcer, due to the absence of frequent etiologic factors of the inception at this age.

Acute Disease↗

Antimicrobial activity and immunological side effects of different antibiotics.

Antibiotics, in addition to killing or inhibiting the growth of microorganisms, may also affect the immune response in many ways. Such effects may be clinically relevant especially when an impairment of immunological functions is seen. This study was designed to analyse the influence of various groups of antibiotics on the host defence system by using different tests in vitro on human or animal cells and in vivo on an animal model. At the same time we analysed the antimicrobial effectiveness of the same antibiotics on over 2800 bacterial strains isolated from our clinical material. Preliminary findings show that a correlation exists between the effect of antibiotics on the immune response, especially the humoral response, and the appearance of resistance in bacteria to these antibiotics.

Animals↗

Further possibilities of using aryloxycarbonic acid derivatives in clinical practice.

In medical practice aryloxycarbonic acid derivatives have been solely used in the treatment of hyperlipidemia. Recently we patented the use of some of these derivatives in the treatment of dermatological diseases. Further analyses showed that these substances stimulated various cells of mesodermal origin including lymphocytes, the principal cells of the immune system. Depending on the concentration some derivatives of aryloxycarbonic acid stimulated or suppressed the proliferative response of lymphocytes, pointing to the possible use of these drugs as immunomodulators in clinical practice as well.

Anticholesteremic Agents↗

Quantitative analysis of immunocomplex deposits in the skin of patients with collagenosis.

The aim of this work was to contribute to identifying more precise diagnostic criteria of particular collagenosis. In a group of 215 patients with clinical diagnosis of collagenosis immunocomplex deposits at the dermal-epidermal junction were determined. The results, when compared with the clinical and histopathological findings, showed that direct immunofluorescence of skin sections of patients with collagenosis confirms the clinical diagnosis significantly more often than does the histopathologic analysis. The advantage of this test suggests that it should be used as an additional diagnostic method for confirming systemic diseases of the collagenous tissue.

Adolescent↗

Alterations in immunological reactivity during pregnancy in mice determined in vitro by lymphoproliferation tests.

Primiparous and multiparous mice, either syngeneically or allogeneically pregnant, were sacrificed at various stages of pregnancy, and the immune reactivity of cells from different lymphatic organs was analyzed by mixed lymphocyte reaction (MLR) and concanavalin A (Con A)-induced lymphocyte proliferation. In the MLR, spleen cells and cells from the axillary lymph nodes of pregnant animals showed similar changes in their response to allogeneic cells during the course of gestation. In comparison to age-matched virgin controls they had an increased reactivity between the 7th and 11th day of pregnancy. During the preimplantation period and the last week of pregnancy, their alloreactivity was comparable to that of the controls. Cells from the para-aortic lymph nodes, which drain the uterus, also showed an increased reactivity at mid-gestation, but in the preimplantation period and third week of pregnancy their alloreactivity was even decreased in comparison to the control animals. When T cell immunocompetence was measured by means of lymphocyte transformation induced with Con A, the pattern of reactivity was completely different. Lymphoid cells from all the above-mentioned tissues showed the highest response to Con A during the preimplantation period, constantly weakening towards term.

Animals↗

Immune responsiveness in offspring of adoptively immunized mothers.

The rate of appearance of cells forming 19S hemolytic antibody (PFC) in the spleens of F1 newborn mice after adoptive anti-paternal immunization of fetuses, newborns and/or their mothers during pregnancy has been studied. An increase in the number of PFC was found at the age of 6 to 11 days in offspring of adoptively immunized mothers. These newborns, even when foster nursed by untreated mothers, still had a significantly higher number of PFC in comparison to the controls. In contrast, adoptive immunization of the newborns themselves resulted in a decrease of PFC during the second week after birth. Several possible explanations for the obtained results are discussed including the putative transplacental passage of immunocompetent cells.

Animals↗

Modulation of mouse anti-SRBC antibody response by placental extracts.

Mouse placental extracts (PE) and corresponding Sephadex G-200 fractions were administered to isogeneic CBA mice along with an optimal immunizing dose of SRBC. Spleen cells were harvested 8 days later and transferred to CBA recipients, subsequently immunized with SRBC. The immunoregulatory activity of spleen cells from PE-treated donors was compared to cells from liver extract (LE)-treated controls or from mice immunized with SRBC only, using Cunningham's PFC direct and indirect tests. Within the dose range used, selective modulatory activities were obtained with cells from PE, but not from LE, treated mice, the latter being comparable to cell transfer effects from donors immunized with SRBC only. Spleen cells from animals injected with low doses of PE (0.25 to 4 mg per mouse) added to immunizing SRBC had a suppressive effect on the primary IgM response of recipients immunized against SRBC. In contrast, when SRBC were given to donor animals with higher doses of PE (8 to 13 mg), transferred spleen cells potentiated the IgM response of the recipients. These opposite suppressive and potentiating activities were found in distinct Sephadex G-200 fractions of 40 and 60 kDa, respectively. When the effect of PE treatment was tested within the same animal, the indirect secondary PFC response following a challenge with SRBC was significantly modified. We observed an overall suppression of the different isotypes after treatment with lower doses of PE or with its 40-kDa fraction. PE doses of 0.5 to 2 mg resulted in a stronger inhibition of IgM than IgG1 production. This phenomenon was also obtained with the 40 KDa fraction. IgG2 responses were significantly reduced by all doses of this fraction. In contrast, all doses of the 60-kDa fraction gave a strong stimulation of IgG2 and IgM responses and a constant suppression of the IgG1 response. This shows a clear dissociation between IgG1 and C'-fixing (IgM, IgG2) antibody classes as far as the influence of placental substances is concerned in their regulation. These data emphasize the relevance of isogeneic placental products as a useful physiological material capable of modulating xenogeneic immune responses (as well as allogeneic systems).

Animals↗

Allogeneic reactivity of maternal lymphoid cells during the course of gestation. Modifications and sex differences in a local GVH assay.

The immune reactivity of lymphoid cells from pregnant mice was studied during the course of pregnancy in primiparous and multiparous animals either " isopregnant " (male and female of same strain) or " allopregnant " (male and female differing at H-2), using a local GVH assay (CBA lymphoid cells injected into (CBA X A/J)F1 recipients). The findings were as follows: The lymphoid cell number in the para-aortic lymph nodes ( PALN ) was increased at all stages of gestation. The peak occurred in the 2nd week in primiparity and as early as 60 h after fertilization in multiparity. PALN cell alloreactivity was weak at the beginning and higher than normal in the third week of pregnancy. Spleen cell alloreactivity was increased in the second week and decreased in the third week in primiparous compared with multiparous animals. Anti-paternal alloreactivity exhibited by spleen cells of allogestation was decreased (as compared to cells of isogestation ) especially in primiparous mice, particularly in the third week. At this time, the anti-paternal alloreactivity of PALN cells was increased. The influence of the recipient's sex on GVHR intensity was reversed when the cells were obtained from a pregnant donor, becoming stronger in male compared with female hybrids.

Animals↗

Lymphocyte subpopulations in the blood and cerebrospinal fluid of multiple sclerosis patients in active disease.

Lymphocyte subpopulations (total T cells, active T cells and B cells) were simultaneously analyzed in peripheral blood and CSF of MS patients. All patients were in active disease, 3 to 4 weeks after first signs of disease activation appeared. Per cent levels and absolute numbers of examined lymphocyte subpopulations in the blood of MS patients were significantly lower than in healthy controls. In MS, the level of active T lymphocytes was lower in CSF than in peripheral blood. The results support our earlier observations relating to the role of active T lymphocytes in the clinical course of disease.

Adult↗

[Malignant melanoma arising from a cystic dermoid teratoma of the ovary].

The primary malignant melanoma of the ovary is a rare kind of neoplasm. This one is in the world literature the eleventh well-documented case having developed in the ovary of a 66-year-old woman. A unilateral ovarian teratoma was removed, within which a malignant melanoma was found. The junctional activity of melanocytes was demonstrated in the epidermis within the teratoma. An extraovarian primary melanoma was not observed. The patient was treated with a bilateral adnexectomy and hysterectomy.

Aged↗