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Biomedical subjects

S Stefanović

Publications and source records attributed to S Stefanović.

At least 19 recordsLinked to original sources

Identification of HLA-A2-restricted epitopes of the tumor-associated antigen MUC2 recognized by human cytotoxic T cells.

Previous studies have shown that self-antigens overexpressed in malignant tissue can provide a basis for a tumor-specific immune response. The mucin MUC2 is strongly overexpressed in all mucinous tumors of colon, breast, ovary and pancreas. In the corresponding normal tissue it is either not expressed (breast, ovary, pancreas) or it is expressed at considerably lower levels than in the mucinous tumors (colon). We therefore investigated whether the MUC2 molecule comprises HLA-A2-binding epitopes recognized by human cytotoxic T cells. Four MUC2 peptides with high affinity and stable binding to HLA-A2 were identified. Those peptides and additionally 3 peptides with moderate binding to HLA-A2 were loaded onto dendritic cells, which were used for stimulation of autologous T cells from healthy donors. Two MUC2 peptides, which belonged to the group of stable binders, induced specific cytotoxic T-cell lines. Target cells loaded with these peptides were strongly lysed in a concentration-dependent and HLA-A2-restricted manner. Our data show that the tumor-associated mucin MUC2 has potential as a target antigen for cytotoxic T cells in patients with mucinous carcinomas.

Amino Acid Sequence↗

[Congenital methemoglobinemia].

This is a report on a case of inborn methemoglobinemia. The disease has been diagnosed in the first week of infant's life. At first it was assumed it was a case of inborn heart defect because of expressed generalized cyanosis, but very soon it was excluded. Values of methemoglobin were extremely high, so three days after birth hereditary methemoglobinemia was diagnosed. Our diagnosis was confirmed by disappearing of cyanosis after ascorbic acid was applied, by values of methemoglobin reductase of the infant and its father, anamnestic data revealing that mother had had temporary cyanosis during her infancy, and satisfactory clinical course of illness.

Diagnosis, Differential↗

Elucidation of the structure of SA-FF22, a lanthionine-containing antibacterial peptide produced by Streptococcus pyogenes strain FF22.

The antibacterial peptide SA-FF22, produced by the pathogen Streptococcus pyogenes strain FF22 was purified and features of its primary and secondary structure were characterised. Mass spectrometry demonstrated the pure peptide had a mass of 2794Da while, amino acid analysis revealed the presence of the unusual, thioether amino acids lanthionine and 3-methyllanthionine; thus SA-FF22 is a member of the group of antibacterial polypeptides termed lantibiotics. Furthermore, amino acid sequencing showed a unique sequence which was blocked at position 23 by a residue of the unsaturated amino acid 2,3-didehydrobutyrine. Carboxypeptidase-Y digestion could be used to demonstrate that serine occupies the C-terminal position only after complete oxidation of the thioether amino acid bridges, suggesting that the three-dimensional structure of the native peptide may prevent access of the enzyme to the C-terminus. Fragmentation of the native peptide with a variety of proteolytic enzymes failed to yield a peptide containing less than all three of the cross-linked lanthionine and methyllanthionine residues and demonstrated that all three thioether bridges overlapped. Analysis of the circular dichroism of SA-FF22 in various concentrations of 2,2,2-trifluoroethanol in water, SDS micelles and in the presence of artificial phospholipid vesicles suggested that there is significant change in its secondary structure from aqueous to lipophilic environments.

Alanine↗

[Zoonoses in Vojvodina. II. Epidemiologic characteristics of leptospirosis in Vojvodina].

On the basis of reported cases of sickness--death due to leptospirosis and the epidemiologic investigation of 38 sick individuals, epidemiologic characteristics of anthropozoonosis in Vojvodina were analyzed. It has been established that this disease is registered in the form of individual cases, mostly in persons belonging to the productive population. Infection usually happens during the summer months and due to contact with contaminated water. High lethality and antibodies of leptospirosis icterohaemorrhagiae in 55.3% of samples of the serum of the sick point to the fact that only clinically severe forms of the disease were registered.

Female↗

[Rubella in Vojvodina. VI. Serologic status of women of reproductive age during the time of endemic manifestations of rubella 1978-1985].

In first phase of a study on congenital Rubella syndrome incidence in Vojvodina population, we examined serologic status of 1225 non-pregnant and 846 pregnant women of generative age, as well as the level of exposure to the Rubella virus. On the basis of antihemagglutinin antibody titre 93.2% of women were found to have antibody titre level above or equal to 1/8. There were no significant differences between the proportions of seropositive women in different age groups (x2 = 1.20; P = 0.88). The percentage of seropositive women varied from 82 to 97% (x2 = 29.85; P = 0.005), according to the year of the investigation. The lowest percentage was registered (1980). Rubella virus susceptibility index was 13.1%. On the basis of proven seroconversion the examination of even Rubella serum samples showed the morbidity rate of 7.18%. The level of exposure of pregnant women to the Rubella virus was 71.0%, during all the period of pregnancy. In such circumstances total Rubella morbidity of pregnant women was 2.13%; the highest level, 21%, was in persons form 18 to 19 years of age. It was not possible to make an analysis of pregnancy outcomes and the consequences in pregnant women.

Adolescent↗

[Epidemiologic characteristics of Lyme borreliosis in Vojvodina].

In the period 1988-1992 in the region of Vojvodina diseases caused by Borrelia burgdorferi were investigated for the first time. This investigation encompassed 398 persons with tick bites. There were 340 clinically healthy and 58 affected by Lyme borreliosis. Lyme borreliosis was registered in all age groups. The youngest patient was 5 and the oldest 75. Erythema migrans, clinical disease marker, was found in 94.8% of affected persons. Rheumatic disorders--arthralgiae were found in 3.5% and Sclerodermia circumscripta in 1.7%. Antibodies to Borrelia burgdorferi antigen were found in 46.9% of 32 patients tested by IFA test. In 55 (94.8%) patients the infestion took place in region of Vojvodina.

Adolescent↗

[Origin of mature granulocytes in the active phase and in remission in various types of acute leukemias].

The problem of provenance of the mature granulocytes in acute myeloblastic leukemia (AML) and in acute lymphoblastic leukemia in their active phase and in remission is still completely unresolved. Mature granulocytes could possibly arise in acute phase of AML from the remaining normal möelopoietic or granulopoietic stem cell or from the very leukemic clone of stem cell which still display, at least partially, the ability to sustain maturation to normal granulocyte level. In ALL, mature granulocyte probably arise from normal granulocyte precursors. In remitted AML, according to opinions of a majority of authors, mature neutrophils descend from normal stem cells. Following the study of 19 patients with AML and 19 patients with ALL, by utilizing the morphological, cytochemical and cytoenzymic properties of granulocytes et the light and electronomicroscopic level the authors have concluded: (1) in comparison with normal granulocytes, granulocytes show in the active AML, hypogranularity as well as a decrease in the activity of all studied enzymes (myeloperoxidase, alkaline and acidic phosphatase and the esterases). (2) In ALL, mature granulocytes do not feature any particular differences in the above pattern as compared with normal granulocytes. (3) In AML remission, the difference between the mature granulocytes and the granulocytes in the active disease is rather slight as compared with the morphological, cytochemical an cytonzymic characteristics. The authors conclude that in a number of patients with AML and in the remitted patients mature granulocytes could possibly originate from the leukemic stem cells which acquired the ability to respond to normal CSF by manner of the gross destruction of the leukemic tumour mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Hereditary factors in the etiology of chronic lymphocytic leukemia].

Leukocyte counts, hemoglobin concentration, PAS positivity index in lymphocytes, leukocyte alkaline phosphatase, karyotype, HLA phenotype as wall as the quality of the cellular and humoral immunity have been studied in 45 patients with chronic lymphocytic leukemia (CLL) and in 103 their closest relatives (sibs, parents). The aim was to detect the possible preleukemic condition in the relatives as a strong propensity towards developing has been previously established in families of patients with CLL. In the CLL patients our studies have confirmed the results of the determination of similar parameters by other authors, namely a higher percentage of PAS+ lymphocytes than normal together with a variety of humoral and cellular immunity disturbances. Regarding the morphological and cytochemical changes in lymphocytes in family members of the CLL patients a higher frequency of PAS+ lymphocytes have been observed: it has been established in over 10 per cent lymphocytes (normally 4-8 per cent) in 31 (30%) examinees and in 14 (13.5%) of these persons the percentage of PAS positivity was equal to that found in CLL patients. Cellular immunity examinations established that in one third of examined E rossete counts counts were lower and in 2 persons the degree of this decrease corresponded to the decrease observed in CLL patients. In one fifth of the examined family members T4:T8 ratio was reduced. In the 13 per cent of the examined M rossete counts were increased, a fact which supports the notion that immunity of B cells exists in relatives of CLL patients. The authors contend that the increased percentage of PAS+ lymphocytes and inadequate functional maturity of the T and B cells in a relatively large number of family members of the CLL patients, intimates that a hereditary disturbance in the lymphocyte make up and their role in the immunity pathways exists and could possibly represent one of the factors implicated in a high frequency of CLL in some families.

Aged↗

[Epidemiologic characteristics of viral hepatitis. II. Hepatitis A in Vojvodina].

In Vojvodina, Hepatitis A occurs endemoepidemiologically. The most intensive epidemiological process takes place in schools, so the specific morbidity of the age group of 7-14 years of age is 4.6 times greater in relation to the average value. The results of bacteriological investigation, as well as those carried out on the pulps of the fingers of pupils of all ages, indicate a high degree of fecal contamination of school environment both in urban and rural communities. The high incidence of asymptomatic infections (1:18), causes the late detection of epidemics, while the inadequate maintenance of personal and general hygiene makes their occurrence and spreading possible.

Adolescent↗

[Ecological characteristics of viral hepatitis. III. Hepatitis B in Vojvodina].

The significance of particular risk factors for hepatitis B virus infection in persons of various ages was analyzed by active epidemiological investigation. Among the diseased children, the largest number of them were mentally retarded and accommodated in special institutions. Sexual and professional exposure to the hepatitis B virus is responsible for a considerable percentage of diseased adults, aged 20-49. In persons over 50 years of age, parenteral medical interventions are the most frequent risk factor. By carrying out proper sterilization in medical practice and vaccination of the exposed categories of the population, a significant reduction of the hepatitis B morbidity rates can be achieved.

Adolescent↗

[Clinical manifestations of acute Q-fever].

The participation of asymptomatic infections and clinical forms of acute Q-fever were analysed, using the active epidemiological investigation of the population affected by Q-fever epidemics. Out of the total number of registered Q-fever cases, the asymptomatic infection was present in 8.36%. The occurrence of asymptomatic infection was statistically more frequent by significance in women than in men. Pulmonary form of Q-fever occurred in 65.20% of the diseased. This clinical manifestation was statistically more frequent by significance in men than in women. The difference between the morbidity rates of Q-fever in regard to sexes could be caused by both the difference in the intensity of exposure to the infection and the difference in clinical presentation and recognition of the disease.

Acute Disease↗