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Z Ilic

Publications and source records attributed to Z Ilic.

13 recordsLinked to original sources
PubMed2002

Proliferation and differentiation of ductular progenitor cells and littoral cells during the regeneration of the rat liver to CCl4/2-AAF injury.

Restoration of centrolobular injury induced by carbon tetrachloride (CCl4), when hepatocyte proliferation is inhibited by treatment with N-2-acetylaminofluorene (AAF), is accomplished by proliferation of ductular progenitor cells, that arise intraportally and extend into the liver lobule. This pattern contrasts to the restitutive proliferation of hepatocytes when AAF is not administered, and the proliferation of non-ductular periportal oval cells follows periportal necrosis induced by allyl alcohol. The expanding ducts stain for alphafetoprotein (AFP), OV-6, pan-cytokeratin (CKPan), and laminin. The neoductular proliferation is accompanied by fibronectin-positive Kupffer cells and desmin-positive stellate (Ito) cells, which may play critical roles not only in controlling proliferation and differentiation of ductular progenitor cells, but also in reestablishing hepatic cord structure. When AAF is discontinued 7 days after injury, clusters of small hepatocytes appear next to the neoductules. Some of these small hepatocytes, as well as some larger hepatocytes adjacent to the ducts, stain for AFP and for carbamoylphosphate synthetase I (CPS-I), suggesting that the ductular progenitor cells may differentiate into hepatocytes when AAF is withdrawn. The restitutive process is facilitated by clearing of the central necrotic zone by infiltrating macrophages and co-migration of mature hepatocytes, with Kupffer cells and stellate cells, into the necrotic zone.

2-Acetylaminofluorene↗
PubMed2002

Antiproliferative activity of some cis-/trans-platinum(II) complexes on HeLa cells.

Purpose of this work was to synthesize several cis-/trans- isomer pairs of the platinum(II) complexes, and study the extent and the mode of their antiproliferative activity on HeLa cells. Six platinum(II) isomer pairs have a general formula cis-/trans-[PtA2X2], where A is ligand: ammonia (NH3), pyridine (Py); and X is ligand: chloride ion (Cl-), bromide ion (Br-), iodide ion (I-), thiocyanato ion (SCN-); four compounds have different structural formulas, and these are cis-/trans-[Pt(NH2OH)2(NH3)2]Cl2, and cis-/trans-Pt(Gly)2, where Gly is bidentate glycinato ligand. Results of the MTT assay, showed that six cis- and one trans-platinum(II) complexes exhibited cytotoxicity (IC50) ranging between 5 and 33 microM. Most of the cis-platinum(II) isomers caused significant alteration of cell cycle phases progression, and induced apoptosis in degree that varied among different compounds, as evaluated using flowcytometry and morphological study. Spectrophotometric analysis (AAS) indicated that there is no correlation between intracellular platinum(II) accumulation and cytotoxicity of tested complexes.

Antineoplastic Agents↗
PubMed2000

Proliferation of hepatic lineage cells of normal C57BL and interleukin-6 knockout mice after cocaine-induced periportal injury.

The cellular response to periportal liver injury, induced by phenobarbital feeding and cocaine injection, is used to compare the restitutive proliferation of hepatocytes, cholangiocytes, and oval cells in the livers of normal control to those of interleukin-6 (IL-6) knockout mice. After this injury hepatocytes in noninjured middle and central zones start to proliferate first, followed by proliferation of cholangiocytes and intraportal oval cells. Proliferation of all cell types peaks at 2 days, but oval cells continue to proliferate and differentiate through days 4 and 6 as they reconstitute the necrotic zone. By day 10, the injured zone is completely repaired, and no dividing cells remain. During the first 3 to 4 days after injury, the number of proliferating hepatocytes, cholangiocytes, and sinusoidal cells is lower in IL-6 knockout mice than in normal mice, whereas the number of dividing oval cells is higher. However, overall repair of the injury is accomplished in the same time period in both groups. During repair of the periportal zone, oval cells acquire differentiation markers of hepatocytes as they cross the zone of injury. In conclusion, the phenobarbital/cocaine injury model is useful to study restitutive proliferation of mouse liver cell lineages. The proliferative response in IL-6 knockout mice shows that IL-6 is not required for proliferation of liver cells; timely repair of liver injury occurs in both normal and IL-6 knockout mice. Increased proliferation of oval cells in IL-6 knockout mice may compensate for the lower proliferation of other liver cell types.

Alanine Transaminase↗
PubMed1999

Respiratory and immunological findings in brewery workers.

BACKGROUND: Occupational exposure of brewery workers to organic dusts such as hops, barley, and brewery yeast has the potential to change respiratory function and immunological status. METHODS: Ninety-seven male workers employed in a brewery plant were studied. The mean age of the workers in this plant was 40 years, the mean duration of their employment was 16 years. In addition, a group of 76 unexposed workers was studied as a control. Respiratory symptoms were recorded. Lung function was measured by recording maximum expiratory flow-volume (MEFV) curves. Immunological testing was performed on all brewery workers and some control volunteers using skin prick testing with hops, barley, and yeast antigens as well as other nonoccupational allergens, and by determining total serum IgE levels. RESULTS: There was a significantly higher prevalence of most of the chronic respiratory symptoms in brewery workers compared to controls (P < 0.01). Occupational asthma, however, was recorded in only 2 (2.1%) of the brewery workers. Logistic regression analysis showed that smoking was the major studied factor responsible for the high prevalence of chronic respiratory symptoms in workers. A large number of brewery workers complained of acute symptoms that developed during the work shift. Lung function tests were decreased compared to predicted. Multivariate analysis of these respiratory function parameters suggested the importance of workplace exposure in explaining lung function abnormalities. Significantly higher prevalences of positive skin prick tests were recorded in 37 brewery workers for molds, hops, and barley than in controls. Increased serum levels of total IgE were documented in 34/97 (45.1%) brewery workers and in 1/76 (2.7%) of the control workers (P < 0.01). However, workers with positive skin prick tests had prevalences of chronic respiratory symptoms and lung function changes similar to those of workers with negative skin prick tests. CONCLUSION: Our data suggest that both smoking and dust exposure in the brewery industry may be responsible for the development of respiratory impairment and immunological reactions.

Adult↗
PubMed1998

Control of mouse hepatocyte proliferation and ploidy by p53 and p53ser246 mutation in vivo.

The effect of expression of the p53 gene, in the presence or absence of the p53ser246 mutation (p53*), on ploidization (image cytometry), proliferation (expression of proliferating cell nuclear antigen and radioactive thymidine histoautoradiography), and apoptosis (in situ detection of DNA fragments) is determined in hepatocytes of p53-null and p53*-transgenic mice. The mouse p53ser246 mutation is equivalent to the p53ser249 mutation found in human hepatomas associated with hepatitis B virus infection and aflatoxin exposure. The hepatocytes of heterozygous or homozygous p53-knockout mice (p53+/-; p53-/-), as well as knockout mice expressing one allele of p53ser246 (p53+/-, p53*; p53-/-, p53*), do not undergo normal polyploidization with aging and show an increase in the number of cycling (G1-, S-, and M-phase) cells. In addition, p53ser246-transgenic mice (p53+/+, p53*; p53+/-, p53*; and p53-/-, p53*) have a greatly increased number of hepatocytes in the G1 phase. No differences in rates of apoptotic hepatocytes are found among any of the mouse groups studied, so the increased proliferation results in a hyperplasia manifested by a increased number of small periportal cells. We conclude that loss of p53 removes blocks in the cell cycle, leading to increased proliferation, whereas expression of the p53ser246 mutation stimulates G0 to G1 and/or M to G1 transition of hepatocytes. Increased proliferation of hepatocytes, combined with no concomitant increase in apoptosis, may in part explain the enhanced development of hepatocellular carcinomas in p53-knockout and p53*-transgenic mice exposed to aflatoxin.

Amino Acid Sequence↗
PubMed1996

Cell kinetics of repair after allyl alcohol-induced liver necrosis in mice.

The cellular kinetics of repair and scarring which occurs after induction of periportal necrosis in mice by allyl alcohol were examined by histology and immunohistochemistry. Thirty-six six-week-old female C57BI/6J mice were injected intraperitoneally with two doses of allyl alcohol on day 0 and tissue sections were taken at various times and stained by haematoxylin and eosin or immunostained for proliferating cell nuclear antigen (PCNA), bile duct/oval cell marker A-6, and DNA fragments (apoptosis). Within 6 hours, periportal necrosis was seen extending to produce large zones of confluent, pan-acinar irregular necrosis, predominantly in the right and medial lobes with sparing of the left and caudate lobes. Restoration of liver mass was accomplished mainly by proliferation of mature hepatocytes in the surviving lobes of the liver (hyperplasia). In the right and medial lobes where necrosis was limited to the periportal zone, there was some, but much less, proliferation of small, oval periportal cells. The large necrotic zones in the right and median lobes shrank and were replaced by granulomatous inflammation. This cellular contribution of liver regeneration in the mouse was different from that previously reported in the rat and provides a means of inducing only a small proliferation of oval cells.

Animals↗
PubMed1995

Developmental control of transcription of the CAT reporter gene by a truncated mouse alphafetoprotein gene regulatory region in transgenic mice.

A truncated mouse alphafetoprotein (AFP) gene promoter/enhancer region was tested for its ability to regulate the expression of the Escherichia coli chloramphenicol acetyltransferase (CAT) reporter gene in the livers of transgenic mice. The AFP regulatory region lacked any AFP gene structural DNA, included one enhancer sequence together with the proximal promoter sequence, and an element believed to be responsible for the postnatal repression of AFP gene transcription. The neonatal livers of AFP/CAT transgenic mice showed a high level of CAT enzyme expression, which was dramatically reduced between 7 and 14 days after birth. The staining of liver sections with anti-CAT antibodies showed that this expression was limited to hepatocytes. In one lineage, reexpression of CAT in the adult liver could be achieved by restitutive proliferation of hepatocytes following partial hepatectomy or CCl4-induced necrosis; reexpression in young animals (3-4 weeks of age) was even greater. These studies show that a truncated AFP promoter/enhancer region functions in a tissue-specific and developmental stage-specific fashion, and may be used to control the expression of other genes in the livers of transgenic mice.

Animals↗
PubMed1995

Knowledge engineering for drug prescribing guidelines.

Prescribing drugs for the treatment of medical conditions is a very common activity for a doctor. Prescribing has enormous economic importance. Costs are rising quickly and there is an urgent need for doctors to have easy assess to advice about the cheapest, most effective therapy. On average 80% of GPs in the UK use a computer for their medical work and the figure is rising rapidly. Currently available systems provide only very simple checks and reminders. More sophisticated advice is provided by our prototype program. The program uses logic engineering to give advice, based on simple protocols for prescribing, tailored both to the condition being treated and the individual patient. The essential logical elements of the prescribing decision are discussed. These simple prescribing protocols may be the final common pathway for prescribing advice from many, more complex protocols for recommendations for drug treatment.

Cost Control↗
PubMed1995

Participation of small intraportal stem cells in the restitutive response of the liver to periportal necrosis induced by allyl alcohol.

To determine the involvement of different hepatocyte populations in response to periportal injury, the restitutive response to allyl alcohol (AA) injury was examined. Adult female Sprague-Dawley rats were injected intraperitoneally (IP) with 0.62 mmol/kg AA, killed at 6, 9, 12, 33, 57, 81, and 153 hours after injection, and the livers were examined for injury and for restitutive proliferation by histology, autoradiography, and immunohistochemistry to detect alpha-fetoprotein (AFP), glutathione-s-transferase-p (GST-p), desmin, leukocyte common antigen, albumin, and monoclonal antibodies to liver cells: OV-6, H-4, and T-6. AA produces variable periportal liver necrosis predominantly at 6 to 12 hours. Proliferation of hepatocytes throughout the hepatic cord is seen early after injury in nonnecrotic areas: predominantly in zone II, but also in zones I and III, including some cells adjacent to the central vein. Within 2 to 3 days the necrotic zones are filled with small cells and by 1 week the liver architecture is essentially restored. During the active restitutive reaction from the immediate periportal rim the following cell phenotypes are seen: null cells: -->(AFP+, OV-6-, GST-p-) cells-->(AFP-, OV-6+, GST-p+) cells-->large (AFP-, OV-6-, GST-p-, H-4+) liver cells. Albumin staining was negative. We conclude that restitutive proliferation of periportal necrosis induced by AA appears to be accomplished by proliferation of intraportal (?stem) cells whose progeny differentiate and eventually repopulate the necrotic zone.

1-Propanol↗
PubMed1994

Dietary cadmium may enhance the progression of hepatocellular tumors in hepatitis B transgenic mice.

The effect of high cadmium levels in the diet on development of primary hepatocellular carcinomas (PHC) in transgenic mice expressing hepatitis B surface antigen (high expressing lineage 50-4) was determined to test the hypothesis that the incidence of PHC in areas of the world with endemic hepatitis B infections is related to the amount of cadmium in the diet. Groups of transgenic 50-4 mice and non-transgenic litter-mates consumed a diet containing high (5 micrograms/g) or low (< 0.05 micrograms/g) cadmium concentrations ad libitum for up to 20 months. Grossly visible and microscopic changes in the livers were examined at different time points after initiation of the cadmium feeding (3, 6, 9, 14-15 and 18-20 months). Although there was no difference in the incidence of tumors in 50-4 male or female mice fed high or low cadmium diets, male mice fed with high cadmium had more poorly differentiated liver tumors than did low-cadmium fed male mice. These observations suggest that dietary cadmium levels do not affect the number of tumors, but may affect progression of the carcinogenic process leading to development of more poorly differentiated tumors. In addition, after uniform liver dysplasia at 6-13 months in all 50-4 mice, 'remodeling' of large areas of the liver with formation of normal appearing liver cords, admixed with dysplastic and nodular areas, was noted in both male and female aged 50-4 transgenic mice.

Animals↗
PubMed1993

Stimulation of HeLa cell growth by physiological concentrations of 4-hydroxynonenal.

The aim of this study was to analyze the growth response of HeLa cells over a prolonged period of time to a single exposure of physiological and supraphysiological concentrations of 4-hydroxynonenal (HNE), a peroxidation product of omega-6-polyunsaturated fatty acids. Furthermore, the growth modulating effect of serum factors, particularly albumin, on the growth pattern was examined. The effects of HNE on the growth rate and viability of the cells, as well as on the incorporation of labelled amino acids were monitored daily over a period of four days. Fetal calf serum not only had a growth stimulating effect but also modulated the action of HNE. In neither respect was albumin able to substitute for serum indicating that the influence of serum was not exerted via an albumin-HNE conjugate. HNE had a clear dose-dependent effect and a distinction could be made between a supraphysiological concentration (100 microM), which was primarily cytotoxic and a physiological range (below 10 microM) which showed growth modulatory effects. These effects consisted of a transient inhibition in the initial phase of the cell growth, which under optimal conditions (in presence of serum) was followed by a period of increased proliferation, compared to untreated control cultures, until confluence was attained. It is suggested that HNE is not only a toxic product of lipid peroxidation, but a physiological growth regulating factor as well.

Aldehydes↗
PubMedDate not supplied

Deep medical knowledge to design clinical guidelines.

Guideline-based care is becoming increasingly important given the surging costs and requirement for quality assessment of health care, and is likely to be a major application of knowledge-based technology into the health sector. Our preliminary experiences with implementing a paper-based guideline in a computer have shown problems that may prevent the dissemination and use by clinicians of the computer-based guideline. Based on these experiences, we propose that deep knowledge, often implicit in guidelines specification, is explicitly considered to provide more adequate support and thus promote its acceptability by clinicians.

Asthma↗