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V Todorovic

Publications and source records attributed to V Todorovic.

17 recordsLinked to original sources
PubMed2005

Latent TGF-beta binding proteins.

Latent TGF-beta binding proteins are multidomain proteins with a common, highly repetitive structural organization and partially overlapping expression patterns. Latent TGF-beta binding protein-1, -3 and -4 bind latent TGF-beta. TGF-betas are normally secreted as latent complexes, consisting of the mature TGF-beta dimer non-covalently bound to its processed propeptide dimer plus a latent TGF-beta binding protein. The latent TGF-beta binding protein is covalently bound to the propeptide. These binding proteins may perform at least two functions: structural, as components of the matrix, and regulatory, as modulators of TGF-beta availability.

Animals↗
PubMed2005

Cyclin A and beta-catenin expression in actinic keratosis, Bowen's disease and invasive squamous cell carcinoma of the skin.

BACKGROUND: Actinic keratosis (AK) has been defined as a precancerous lesion or an early phase in the evolution of squamous cell carcinoma (SCC) and histological changes seen in the individual cells of an AK are indistinguishable from those seen in SCC, which invade the dermis. Cyclin A is an increasingly utilized proliferation marker that has functions in both S phase (DNA replication) and initiation of mitosis, whereas alterations of beta-catenin, the molecule involved in cell-cell adhesion and in signalling transduction, could promote invasive and proliferative capacities of malignant tumours. OBJECTIVES: To determine cyclin A and beta-catenin expression pattern in cutaneous SCC and in in situ lesions classified as keratinocytic intraepidermal neoplasia (KIN) and, using traditional terms, as AK and Bowen's disease (BD), and to analyse it in relation to SCC differentiation, diameter and thickness. METHODS: Immunohistochemical staining was performed on 110 formalin-fixed paraffin-embedded tissue samples with the streptavidin-biotin technique using antibodies to cyclin A and beta-catenin. On histological examination, 53 lesions were diagnosed as AK, 16 as BD and 41 as SCC-11 well differentiated (WD), 16 moderately differentiated (MD) and 14 poorly differentiated (PD). Using KIN classification, 22 lesions were KIN1, 23 were KIN2 and 24 were KIN3. For cyclin A, distribution and labelling index (LI), and for beta-catenin, level of membranous staining and presence of aberrant (nuclear/cytoplasmic) localization were examined. RESULTS: Diffuse cyclin A presence was observed more frequently in BD than in AK (P < 0.0001) or SCC (P = 0.0002), and in SCC-PD compared with SCC-WD (P < 0.0001) or SCC-MD (P = 0.0003). Differences between KIN3 and KIN2, as well as KIN3 and KIN1 lesions, were statistically significant (P < 0.0001), and the same result appeared when KIN1 and KIN2 cases were grouped and compared with those of KIN3 (P < 0.0001). Cyclin A LI was significantly lower (P < 0.05) in AK than in BD or SCC, but no difference between BD and SCC was found, and LI in BD was even higher than in SCC-WD or SCC-MD, while analysis regarding SCC differentiation and KIN classification revealed the same correlation as for the cyclin A distribution. Reduced or absent beta-catenin membranous staining was found in 90 cases (81.8%), more often in SCC than in AK (P = 0.03) or in AK and BD grouped together (P = 0.02). There was no statistical difference between SCCs of various level of differentiation, or between different KIN grades. Diffuse loss of membranous beta-catenin staining showed 36 lesions (32.7%), more frequently SCC than AK (P = 0.003) or AK and BD grouped (P = 0.006), as well as SCC-PD compared with SCC-WD (P = 0.01) and SCC-MD (P = 0.03), whereas all KIN comparisons remained nonsignificant. Aberrant beta-catenin cellular localization demonstrated 28 lesions (25.5%), most often in the basal or peripheral parts and in the lesions with diffuse beta-catenin loss (P = 0.009), but revealed no correlation with the histological type, SCC level of differentiation or KIN grades. Diffuse loss of membranous beta-catenin staining was found to be significantly more frequent in SCC thicker than 4 mm (P = 0.03), while all other comparisons between cyclin A or beta-catenin with the tumour size remained nonsignificant. Cyclin A LI was higher in cases with diffuse loss of membranous staining (P = 0.001) or with aberrant cellular localization of beta-catenin (P = 0.002). CONCLUSIONS: Cyclin A LI showed greater difference between AK and BD than between BD and SCC, suggesting that increased proliferation (measured by cyclin A LI) characterizes progression of in situ lesions from AK to BD, whereas reduced beta-catenin expression separates more clearly SCC from the in situ lesions. Diffuse pattern of loss of membranous beta-catenin staining correlated better with the type of lesion, SCC differentiation and tumour size than reduced expression in general or aberrant cellular localization of beta-catenin. KIN classification does not seem to be supported by our findings, except when KIN1 and KIN2 lesions (in situ, partial thickness) are grouped.

Adult↗
PubMed2005

The significance of lymphonodal micrometastasis in the patients with gastric adenocarcinoma.

Micrometastasis is defined as microscopical deposit of malignant cells, less than 2mm in diameter, separated from the primary tumor. This does not include discontinous growth in peritumoral region, but include microinolvement of regional lymph nodes. The literature on micrometastases, with special resperct to nodal micrometastasis, and their implications in gastric adenocarcinoma have been reviewed. Immunohistochemical detection offer the best accuracy for detection of nodal micrometastasis. Molecular techniques are more sensitive than method of immunohistochemical detection, but methods are compromised with false positive results caused by various sources of biological contamination. It is more than obvious that there is no definite agreement neither about risk factors, nor definitive clinical significance of micrometastatic node involvement in the patients with gastric adenocarcinoma. At present, the role of occult lymph node involvement proved its significance in two major fields: defining criteria for limited surgical dissection in the patients with early (sm) carcinoma in respect to detection of micrometastatic tissue in sentinel lymph node, and distinguishing the category of pN0 (Mi+) patients with potential benefit of postoperative adjuvant therapy.

Adenocarcinoma↗
PubMed2004

Anti-CagA and anti-VacA antibodies in Helicobacter pylori-infected patients with and without peptic ulcer disease in Serbia and Montenegro.

BACKGROUND: The expression of two Helicobacter pylori proteins, CagA and VacA, is associated with more severe pathogenesis and clinical outcomes of the infection. However, this association varies among geographical regions and ethnic groups. We therefore evaluated CagA and VacA seroprevalence in H. pylori-positive dyspeptic patients in Serbia and Montenegro. METHODS: In 173 consecutive dyspeptic patients referred to endoscopy (67M, mean age 49 +/- 15, 76 smokers), immunoblot assay was used to detect serum antibodies against CagA and VacA. Presence of H. pylori infection was assessed using a rapid urease test (RUT), routine histology and serology (anti-IgG ELISA). Duodenal ulcer (DU) was diagnosed in 28, gastric ulcer (GU) in 3 and non-ulcer dyspepsia (NUD) in the remaining 142 patients. RESULTS: 129 (74.6%) patients were H. pylori-positive, 27 (96.4%) with DU, 3 (100%) with GU and 99 (69.7%) with NUD (P < 0.01); 121 (93.8%) patients carried anti-CagA antibodies and there was no difference between the DU and NUD groups. VacA antibodies were detected in sera of 50 (38.75%) and were more prevalent in patients with DU compared to the NUD group (P < 0.05). CONCLUSIONS: In Serbia and Montenegro there is high seroprevalence of CagA-positive H. pylori strains in dyspeptic patients with and without peptic ulcer, while VacA-positive strains are more closely related to peptic ulcer disease.

Adult↗
PubMed2001

Detecting and managing undernutrition of older people in the community.

Undernutrition is an important public health issue which is frequently undetected and untreated. Disease and illness are the major causes of undernutrition in this country, and older people are a particularly vulnerable group. Effective screening is needed to reduce the prevalence of malnutrition in older people and when this is established, action can then be taken to address the problem. Community nurses and the primary care team have a key role to play in making this happen. The recently developed Malnutrition Advisory Group (MAG) nutrition screening tool, for adults will help community staff and primary care staff to identify those older patients most at risk of malnutrition in the community. Routine nutrition screening of vulnerable individuals is the first stage in raising standards of nutrition care. Further improvements can be made through the development of appropriate nutritional guidelines, clinical risk management strategies provides opportunities to highlight the importance of nutrition care of older people.

Aged↗
PubMed2000

Postoperative pathological examination of colorectal cancer.

The close cooperation of the surgeon and the pathologist in clinical practice and research of colorectal cancer was far established. The histopa-histopathological report has to include all important information in relation to tumour classification, prognostic factors and surgical procedure. This is the starting point for further treatment, estimation of prognosis and treatment results, indicator of oncological quality of surgical procedure and the most important contribution to increasing knowledge of clinical pathobiology related to colorectal cancer. To reach these goals the pathologist should follow some of up-dated histopathological protocols for the examination of specimen removed from patients with colorectal carcinoma. Most of the proposals and international standards are presented in detail. The applying of three main classifications for colorectal carcinoma is mandatory, i.e. histopathological classification, the disease stage (pathoanatomic extension) classification and residual disease classification. It seems that the first and most important step is R (residual disease) classification, serving as the most reliable determinant in further treatment, prognosis and in assessment of surgical treatment. The focus of surgery on R0 category subgroup of patients is presented in relation to the disease stage as second proven prognostic factor, strongly influencing the prognosis and adjuvant therapy options. The detection and significance of minimal residual disease, mainly occult micrometastases in examined lymph nodes are essential for more accurate staging of the disease. Our own data from pilot study confirmed the significant stage migration (Will Rogers phenomenon of "up-grading"). Using combination of serial sectioning and immunohistochemical reactivity of anti-cytokeratin antibody to scattered micrometastatic foci in lymph nodes and perirectal fat, we have shown the presence of minimal residual disease in 23.53% of R0 pT3 pN0 primary classified cases. Correlation to other probable and possible histological independent prognostic factors is discussed, as well as the most significant molecular prognostic markers.

Carcinoma↗
PubMed1999

Replication origins of mammalian chromosomes: the happy few.

Replication of eukaryotic cell genomes is a tightly controlled process occurring once and only once per cell cycle. Replication initiates at several thousand origins, whose cis-acting sequences and trans-acting proteins have been partially characterized in the yeast S. cerevisiae in the last few years. In contrast, identification of origins of DNA replication in mammalian cells have proven much more difficult. Currently, less then 20 bona fide mammalian origins have been identified, of which only few characterized in detail. Here we discuss the available methods for origin identification in mammalian DNA and the main results, sometimes controversial, so far generated by their application. In particular, we review the currently available information concerning the three best characterized origins, namely those in the lamin B2 and b-globin gene domains in human cells and the one located downstream of the dihydrofolate reductase gene in hamster cells.

Animals↗
PubMed1998

Den1, den2 and den3, ATP-inhibited deoxyribonucleases from Dropsophila embryonic nuclei.

Three Drosophila embryonic deoxyribonucleases, designated den1, den2 and den3, are identified in nuclear extracts separated by glycerol density gradient centrifugation. Den1, removes short products from the 5'-ends of single-stranded DNA or double-stranded DNA with either blunt or 5'-recessed termini. Den2 is inactive with single-stranded DNA and acts as 3'-exonuclease with double-stranded DNA possessing either blunt or 3'-recessed termini. Den3 preferentially uses partial duplex DNA containing single-stranded gap and it catalyzes hydrolysis, in 3'-5' direction, of one of the shorter strands that flank the gap. Nucleolytic activities of den1, den2 and den3 are inhibited with ATP.

Adenosine Triphosphate↗
PubMed1997

Characterization of a helicase, DHEL III, from Drosophila melanogaster embryonic nuclei.

Nuclear extracts prepared from Drosophila preblastoderm embryos contain a nucleoside 5'-triphosphate-dependent helicase that unwinds circular or linear partial duplex DNA substrates and moves along the DNA in 3' to 5' direction. The helicase reaction is supported with both nucleoside and deoxynucleoside 5'-triphosphates and requires divalent cations. Optimum activity in vitro is achieved with dATP or ATP and with MgCl2. In glycerol density gradients, embryonic enzyme migrates as a single peak of around 90kDa and it is the most prominent DNA-unwinding activity detectable in nuclear extracts prepared from embryos 0-2 hours after egg laying. In embryos collected 2-4 hours after egg laying this DNA unwinding activity increases and then gradually decreases in embryos collected 4-8 and 8-16 hours after egg laying.

Animals↗
PubMed1996

Rat pinealocyte reactive response to a long-term stress inducement.

The pineal gland-reactive response to long-term multifactor stress inducement performed by 18 h immobilization was found in the occurrence of different pinealocyte forms--cells of the basal activity, functionally animated cells and cells assumed to be threatened by an irreversible injury. Functionally animated pinealocytes were recognized as entities of neuroendocrine-like and ependymal-like activities displaying an episode of their initially increased secretory activity determined by Golgi apparatus and succeeded by a period determined by the storage of compounds arising from the cisterns of the granular reticulum. The domination of the pinealocytes with neuroendocrine-like activity was considered to evince a stimulated, peptidergic-mediated pineal gland activity. The adrenocorticotropic hormone-reactive secretion, employed as the evaluation parameter in morphofunctional observations, corroborated the morphologically estimated increased pineal gland activity in long-term stress inducement.

Animals↗
PubMed1996

Erythrophagocytosis by brown adipocytes of rat interscapular tissue.

In this investigation the following phenomena were observed: 1. Rat interscapular brown adipocytes were found to be capable of erythrophagocytosis; 2. Before leaving the capillary lumen, erythrocytes took some material from the blood plasma by endocytosis and passed the endothelial junction carrying endocytotic vacuole. Some erythrocytes were in transit: the so-called "head" was in the process of engulfment by brown adipocytes while the rest of the cell had not left the capillary lumen. Fragmentation of erythrocytes was observed during passage through the endothelial junction as well as in the cytoplasm of adipocytes. 3. In some brown adipocytes erythrocytes retained the same shape as in the capillary, but in many cases they exhibited unusual form. Intracytoplasmic erythrocytes were seen in a semithin sections stained with toluidine blue. 4. Erythrocytes either became cells which phagocytized mitochondria and lipid droplets before their transformation into lipofuscin bodies or they were degraded into ferritin-like particles observed (on unstained sections) in the mitochondrial matrix, intercristal space, on the periphery of lipid droplets and in brown adipocyte cytoplasm.

Adipose Tissue, Brown↗
PubMed1996

The effects of long-term low-protein intake on gastrin cells of the rat antral mucosa during adulthood.

The effect of experimental protein malnutrition on gastrin producing cells in the antral part of the stomach was studied in male Wistar rats. Isoenergetic diets containing 25% (C-25) or 6% (PD-6) were given in isocaloric amounts during a 4-month experiment. All rats were offered drinking water ad libitum. The results showed that the long-term protein diet did not produce changes in the gastrin cell number. At the ultrastructural level G cells exhibited a decreased size of the nucleus. They were found to have an increased total granule volume density but the volume density of dense-cored granules was lower. The serum gastrin levels were significantly lowered by feeding the low protein diet. These changes are compatible with decreased functional activity of G cells under long-term protein deprivation.

Animals↗
PubMed1995

Immunomorphological characteristics of renal cell carcinoma.

Immunomorphological characteristics of 27 renal cell carcinoma (RCC): 18 clear cell, 6 granular (chromophilic), 2 chromophobe, 1 spindle cell (sarcomatoid) as well as of 1 oncocytoma, were analyzed. The investigation was performed on cryostat sections by immunoperoxidase technique applying a panel of monoclonal antibodies which defined: proximal (TNE3, TN5, 5D9) and distal (TN8, TN9, 7C2) tubular antigens; intercellular adhesion molecule 1 (ICAM1); HLA class II (-DQ, -DR and -DP) antigens, intermediary filaments (cytokeratin and vimentin); and antigens on tumour infiltrating mononuclear leucocytes (TT1, TT2 and LeuM3 for CD4, CD8 and CD14 antigens, respectively). All RCC with exception of chromophobe co-expressed cytokeratin and vimentin. In addition, they were usually positive for all proximal and two distal tubular markers (TN8, TN9) indicating primitive cells which could differentiate into the epithelium of both parts of tubule system as the most probable originators of in RCC. Almost all RCC but the chromophobe aberrantly expressed HLA class II antigens which great variability from case to case. The presence of HLA-DR antigens was more intensive and widespread than of HLA-DQ and -DP antigens. Expression of ICAM1 mostly correlated with presence of HLA class II antigens, particularly with -DR on tumour cells of RCC. HLA-DR antigen expression was always more prominent than mononuclear cell infiltrate (among which macrophages prevailed over T cells) which could suggest that increased histocompatibility antigen expression precedes mononuclear cell influx. In contrast to all other RCC, chromophobe tumours had quite distinct features revealing the most intense reaction with 7C2 (MAb that produced the weakest reaction with other tumour types), absence of vimentin and very weak reaction with antibodies for HLA class II Ag and ICAM1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Oxyphilic↗
PubMed1991

HI-6 in man: efficacy of the oxime in poisoning by organophosphorus insecticides.

The efficacy of the oxime HI-6 was studied as a treatment for organophosphorus poisoning. HI-6 was given four times daily as a single intramuscular injection of 500 mg accompanied by atropine and diazepam therapy. Oxime treatment was started on admission and continued for a minimum of 48 h and a maximum of 7 d. HI-6 rapidly reactivated human blood acetylcholinesterase inhibited by dimethoxy organophosphorus compounds, while the dimethoxy-inhibited enzyme was mainly resistant to the treatment by HI-6. Although both HI-6 and pralidoxime chloride reactivated the red blood cell cholinesterase in quinalphos-poisoned subjects, the return of enzyme activities was more rapid following the use of HI-6. The general improvement of poisoned patients, which was sometimes more rapid than the rise of acetylcholinesterase activity, pointed to direct pharmacological effects of HI-6. No undesirable side-effects were noted in patients when HI-6 plasma concentrations were maintained at levels far above the 'therapeutic' concentration for up to 7 d.

Adult↗
PubMedDate not supplied

Umbilical metastasis (Sister Joseph's nodule) as a first sign of a disseminated ovarian carcinoma: comparative immunohistochemical analysis of primary tumor and its metastases.

The case of a 46-year-old female with umbilical metastasis as a first sign of an ovarian carcinoma is reported with the results of immunohistochemical analysis of primary tumor and lymph node and umbilical metastases. All specimens were positive for cytokeratin 7, CA 125, E-cadherin, alpha-, beta-, and gamma-catenin, as well as for MSH2. Staining with cytokeratin 20 and MLH1 was negative, and Ki-67 labeled from 5% (in the center of the lesions) to over 25% (at the periphery of the lesions) of the nuclei. Beta-catenin showed membranous positivity in the central parts and absence of staining at the periphery of ovarian tumor and umbilical metastasis, whereas lymph node metastasis presented with uniform reaction throughout. The results of immunohistochemical staining could point to the mechanisms employed by malignant tumors during invasion and growth of metastasis and suggest the possible role of the microenvironment in the expression of some adhesion molecules on tumor cells.

Biomarkers, Tumor↗
PubMedDate not supplied

Colonic vasoactive intestinal polypeptide (VIP) in ulcerative colitis--a radioimmunoassay and immunohistochemical study.

BACKGROUND/AIMS: In this study, we present radioimmunoassay data describing the concentration of Vasoactive Intestinal Polypeptide (VIP) in both plasma and colonic biopsies, as well as immunostaining of VIPergic innervation in mucosal biopsies of normal subjects and patients with ulcerative colitis (UC). PATIENTS AND METHODS: Thirty three patients with UC and 17 healthy subjects were investigated. All UC patients suffered from active disease. Fasting circulating levels of VIP in plasma as well as tissue concentrations were measured by radioimmunoassay. For the immunohistochemistry, polyclonal antibody against VIP and the streptavidin-biotin peroxidase complex technique were carried out. RESULTS: Overall plasma VIP concentrations in the UC patients were similar to those in the controls. Significantly decreased concentrations of VIP were found in UC of rectum compared to the normal tissue. However, both plasma VIP values and tissue concentrations were found to be significantly lower in patients expressing minimal or mild active disease according to clinical activity index (AI) and histological activity index (HAI), but marked increase of plasma VIP was clear in UC patients with moderate or severe AI and HAI. There was a trend towards increased tissue concentrations of VIP in the group of patients with moderate or severe AI and HAI. Our immunohistochemical analysis of VIP fibers and nerve cell bodies revealed consistently weaker VIP-immunoreactivity in the rectum in UC patients with minimal or mild HAI. Simultaneously, in the rectal biopsies from UC patients with moderate and severe disease, the fibers in the lamina propria and ganglion cells in the submucous plexus were markedly increased in density and in degree of immunostaining. Very strong immunoreactivity was also found in inflammatory cells of the lamina propria as well as in the epithelial layer of the biopsies from UC patients with obvious disease. CONCLUSIONS: Our study shows clearly the heterogeneity in the response of VIP plasma level as well as rectum concentration and distribution in UC patients at different stages of the active disease. The possible role of VIP in the colon suggests that further studies of the alterations of this gut peptide may be useful in the understanding of UC pathophysiology.

Adult↗