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Biomedical subjects

M Sarić

Publications and source records attributed to M Sarić.

At least 19 recordsLinked to original sources
PubMed2006

The second cysteine protease inhibitor, EhICP2, has a different localization in trophozoites of Entamoeba histolytica than EhICP1.

The genome of Entamoeba histolytica contains two genes encoding inhibitors of cysteine proteases of the chagasin family. In contrast to that of EhICP1, the derived primary structure of the second inhibitor, EhICP2, possesses a typical N-terminal signal sequence. Processed EhICP2 is as weakly related to amoebiasin-1 (27% identity) as to chagasin (identity 30%), indicating a different evolutionary origin of both amebic genes. By Northern blots, we confirmed the expression of the ehicp2 gene, and in Western blots, the presence of the 11.5-kDa protein in trophozoite extracts was demonstrated. The inhibitor localized to large intracellular structures clearly differs from those containing EhICP1 as shown by indirect immunofluorescence. Recombinant EhICP2 significantly inhibited the cysteine protease activity of the amebic cell extract but with a lower extent than EhICP1. An overlay assay using a crude trophozoite extract demonstrated binding affinity of the amebic cysteine protease EhCP1 to EhICP2.

Amino Acid Sequence↗
PubMed2005

Identification of EhICP1, a chagasin-like cysteine protease inhibitor of Entamoeba histolytica.

Based on the Entamoeba histolytica genome project (www.sanger.ac.uk/Project/E_histolytical/) we have identified a cysteine protease inhibitor, EhICP1 (amoebiasin 1), with significant homology to chagasin. Recombinant EhICP1 inhibited the protease activity of papain and that of a trophozoite lysate with Ki's in the picomolar range. By immunocytology, we localized the endogenous approximately 13 kDa EhICP1 in a finely dotted subcellular distribution discrete from the vesicles containing the amoebic cysteine protease, EhCP1 (amoebapain). In an overlay assay, we observed binding of recombinant EhICP1 to EhCP1. As a heptapeptide (GNPTTGF) corresponding to the second conserved chagasin motif inhibited the protease activity of both papain (K) 1.5 microM) and trophozoite extract (Ki in sub-mM range), it may be a candidate for the rational development of anti-amoebiasis drugs.

Amino Acid Sequence↗
PubMed2004

Effects of X-ray irradiation on the overexpression of HER-2/Erb-B2 on breast cancer cell lines.

Irradiation is the conventional treatment modality for cancer patients. However, besides its cytotoxic effects on malignant cells it might also affect the biology of surviving cells. Since overexpression of HER-2 receptors on malignant cells is a prerequisite for the therapeutic efficacy of Herceptin, it seems important to know whether previous irradiation changes their overexpression. The experiments performed in this work were aimed to determine whether X-ray irradiation of MDA-MB-361 and MDA-MB-453 breast carcinoma cell lines, besides its cytotoxic action, affects the overexpression of HER-2 protein. Determination of the cytotoxic effect of X-ray irradiation was done using trypan blue test. The breast carcinoma cell responsiveness to herceptin treatment in the presence of 10% fresh human serum (from healthy volunteer's) in the presence or absence of 25 microg/ml of herceptin, in vitro before and after cell-irradiation, was evaluated by MTT test. The degree of HER-2 overexpression was determined by immunocytochemistry, using DAKO HercepTest. Preliminary results obtained in this work showed that X-ray irradiation, besides its cytotoxic effect on malignant cells, could lead to overexpression of HER-2 receptors on (initially by immunocytochemistry, HER-2 negative) tumor cells, indicating change in biology of treated tumor cells. Further investigation in this direction will probably be helpful to elucidate this task in order to improve the selection of irradiated patients for Herceptin therapy.

Antibodies, Monoclonal↗
PubMed2000

[Cancer of the respiratory organs with respect to environmental and life style factors in the areas of Split, Solina and Kastela] Citation].

This investigation focused on Split and the industrial area of the Solin-Kastela bay, as it has been known for cement production for over 130 years, and for asbestos cement production for some 80 years. Environmental factors (air pollution) and lifestyle (cigarette smoking and alcohol consumption) were investigated in persons who died of cancer of respiratory organs. The aim was to see what is the combined effect of several noxious factors and how it may increase the risk of cancer of the respiratory organs. The sample of 473 subjects was randomly selected from 1490 persons who died of cancer of respiratory organs in the studied area between 1970 and 1990. The data on the subjects' lifespan, smoking habit, and alcohol consumption were obtained by interviewing their families. Environmental data showed that 5% had lived in an area with industrial air pollution (cement, asbestos-cement) for up to 15 years, 19% from 16 to 29 years, 33% from 30 to 49 years, and 44% for 50 years and over. The number of those exposed to air pollution for 50 years and over ranged from 36% to 68% in different districts. Of 473 subjects 85% had been cigarette smokers; 42% had smoked over 40 cigarettes a day, 83% had smoked for over 30 years, and 74% of subjects had consumed alcohol. The largest number of persons in the studied group were in the category with the longest exposure to air pollution and the longest and most intensive smoking experience. This indicates the possibility that simultaneous action of environmental factors and lifestyle may increase the risk for the development of cancer of respiratory organs. Smokers showed a significant shift (in percentage) towards shorter length of living in the studied area. That suggests that the risk of cancer of respiratory organs was greater in cigarette smokers than nonsmokers, regardless of the fact that both were exposed to comparable air pollution.

Adolescent↗
PubMed1999

Occupational health services in Croatia.

A short historic review of the development of occupational health problems and activities in Croatia as well as of relevant legislation, organization of occupational health services, and approaches to education is given. Workers' morbidity patterns are also briefly discussed. The present orientation and foreseeable needs and tasks are critically evaluated. The role of research in the development of occupational health practice is emphasized.

Croatia↗
PubMed1999

[Occupational medicine worldwide and in Croatia].

The development of occupational medicine, its complexity and international position as well as the actual and anticipated tasks connected with modernisation of industry, workers' health protection and humanization of work is presented. Education in the field of occupational medicine is also evaluated. Eighteen countries: ten in Europe, United States of America, Canada, Brasil and Chile from the area of South America, Israel, Japan, China and Singapore in Asia are included in the review. At the end, the development of occupational health services in Croatia, its present organisation, legislation, education and training, future needs and goals are shortly discussed.

Croatia↗
PubMed1999

Health effects studies related to occupational and environmental exposure.

This paper describes adverse health effect studies conducted at the Institute for Medical Research and Occupational Health since its foundation fifty years ago to the present day. The presentation of the studied problems is based mainly on the type of exposure--occupational or environmental--and partly on disease entities. The review is organised around the following topics: metals, organic solvents, and other organic chemicals, pneumoconioses and occupational pneumopathies, bronchial asthma and nonallergic bronchoconstrictive impairments, chronic nonspecific lung disease, studies of respiratory effects of exposure to air pollutants in schoolchildren, other problems concerned with pathology of work and workers' health protection, epidemiology of chronic noncommunicable diseases in general population groups, criteria for the assessment of disability and ability to work. The review concludes with a short description of achievements at the national and international level, and gives an anticipation of future research needs. Literature references provide a selection of publications on research activities presented herein.

Environmental Pollutants↗
PubMed1998

Human Exposure Assessment Location (HEAL)--historical review.

The first part of the review describes events and newly acquired knowledge that anticipated the making of the HEAL project and its preparatory phase. The pilot study relied on the belief that the total exposure assessment should take into account different pollutants and their relative contribution in the human intake from different environmental media such as air, drinking water, food chain, and soil. The pilot study included exposure assessment to lead and cadmium, nitrogen dioxide, hexachlorobenzene, and DDT-complex. Concurrently, another study on indoor air quality in Kenya and Gambia took place. In its second phase, the project evaluated the actual trends and outlined potential future directions. It was decided that the project should focus on the promotion of exposure studies, particularly in developing countries, and that it should establish a closer relation with health risk assessment and environmental epidemiology. The last part of the review describes the participation of the Institute for Medical Research and Occupational Health in Zagreb, Croatia in the project and in related research activities performed after the pilot phase.

Developing Countries↗
PubMed1997

Respiratory impairment among children living in the vicinity of a fertilizer plant.

The study included 162 second-grade children (85 boys and 77 girls) aged 8-9 years, attending two schools in an area with a fertilizer production plant, and 59 second-graders of the same age (32 boys and 27 girls) from a small neighbouring town located 20 km west of the plant, without any particular source of pollution. During the period from December 1990 to May 1991 the incidence of acute respiratory diseases was surveyed in children and their family members, and forced expiratory volumes were measured in selected second-graders in December 1990 and April 1991. In the area with the fertilizer plant as well as in the compared area ammonia, hydrogen fluoride, nitrogen dioxide, total suspended particulate matter and smoke were measured daily in ambient air and inside the school buildings. The mean concentrations of pollutants during the study period were below the recommended limits, with only a few exceptions, but daily fluctuations, particularly of ammonia and hydrogen fluoride in the area around the plant happened to exceed these values. The observed differences in the levels of air pollution correlated to some extent with the health parameters followed up during the study period. The incidence of acute respiratory diseases corresponded to the registered differences in the exposure to measured pollutants. Forced expiratory volume values in the compared groups of children did not consistently reflect the differences in exposure levels.

Air Pollution↗
PubMed1997

Metal exposure studies: role of toxicology and epidemiology in public health policy.

Following the idea of interrelated role of epidemiology and toxicology in risk assessment and dose response evaluation, this paper presents certain experiences from the authors' studies of health effects of environmental exposure to lead and manganese. Epidemiologic observations of adverse effects on female reproductive integrity in a lead smeltery area agree with the experimental data. Animal studies show that the adverse reproductive effects in females are time and dose-related, and reversible after exposure has ceased. Field studies show that effects of manganese on the respiratory system in a polluted region are dose, age and season-related. Cytotoxic effects of manganese, including the inhibitory effect on alveolar macrophages described in in vitro studies on mammalian cells confirm the epidemiologic observations. Authors conclude that in the process of risk assessment, toxicology and epidemiology have to act together. Available human data should be combined with experimental findings and data on the mechanism of toxic action.

Abortion, Spontaneous↗
PubMed1996

Malignant tumours of the gastrointestinal tract in an area with an asbestos-cement plant.

Data on persons who died of cancer of the gastrointestinal tract in a Croatian coastal area with an asbestos-cement plant were analysed for the period 1970-1990. By poll method applied to the families of deceased subjects, additional data on occupation, lifestyle, educational level, length of resistance and cancer mortality among relatives were collected. The investigation showed that in the study area, but also in certain narrower locations within it (subarea settlements), some of the tumours studied occurred at higher rates than expected. Although not conclusive, these findings may indicate a role of environmental exposure to asbestos, particularly in the occurrence of peritoneal mesothelioma.

Age Factors↗
PubMed1996

Continuous infusion of DL-alpha-difluoromethylornithine and improved efficacy against a rat model of Pneumocystis carinii pneumonia.

The rapid depletion of Pneumocystis carinii polyamines caused by in vitro exposure to DL-alpha-difluoromethylornithine (DFMO; also called eflornithine or Ornidyl) and the rapid repletion following removal of this drug suggested that the in vivo efficacy of DFMO against P. carinii pneumonia (PCP) may be limited by troughs in drug concentration resulting from the schedule of administration. This led to the prediction that, compared with the response to the standard animal protocol of administering DFMO in drinking water, the response of a rat model of PCP to DFMO would be lessened by bolus administration and improved by continuous infusion. These predictions were confirmed. Intraperitoneal bolus administration of up to 3 g of DFMO kg of body weight-1 was completely ineffective, although this dose has been shown to be effective when given in the drinking water. Conversely, continuous infusion improved the response against PCP seven- to ninefold over the response to drinking water administration. These findings suggest that, compared with the standard clinical investigational protocol for treatment of PCP with DFMO given in four divided daily doses, continuous infusion combined with monitoring of drug concentrations in plasma may improve efficacy and/or reduce the already low rate of adverse effects.

Administration, Oral↗
PubMed1996

[Respiratory system reactions to organic aerosol exposure].

The effects of organic aerosols (coffee, teas, spices, confectionery, soy, animal feed) on the respiratory system of workers occupationally exposed to these aerosols are presented. Described are possible mechanisms responsible for the development of respiratory impairment. Our studies indicate the possibility of development of respiratory impairment in exposed workers. The prevalence of chronic respiratory symptoms and diseases varied from 2.7 to 56.3% and of acute symptoms from 9.9 to 78.9% of exposed workers. Statistically significant acute reductions of ventilatory capacity (FVC, FEV1, FEF50, FEF25) were recorded during the work shift. Described are some immunological changes which can develop in exposure to organic aerosols. Experimental studies with water organic dust extracts on isolated guinea pig trachea suggest that bronchoconstrictive changes in humans may be reproduced in non-sensitized guinea pigs. The need for taking preventive medical examinations in order to prevent development of respiratory and/or immunological impairment is stressed.

Adult↗
PubMed1996

[Byssinosis--an occupational disease of textile workers].

Byssinosis as a nonspecific chronic respiratory disease in textile workers exposed to cotton, hemp and flax is described. Pathogenesis and ethiologic factors responsible for bissynosis are listed. Clinical symptoms of byssinosis and differential diagnosis with occupational asthma are presented. Characteristic functional changes of ventilatory capacity in textile workers are described. Clinical and functional criteria for diagnosis of byssinosis are presented. Particular emphasis is given to preventive medical and technical measures in order to prevent the development of respiratory diseases in textile workers.

Byssinosis↗
PubMed1996

[Mechanisms in the onset of nonspecific respiratory diseases caused by air pollutants in the work environment].

Mechanisms responsible for the development of occupational non-specific respiratory disease are presented. The roles of factors such as changes in airway smooth muscle, changes in airway mucosa and submucosa, altered regulation of the autonomous nervous system and the presence of an inflammatory process in the airways are described separately. Those changes may induce an increased reactivity of the bronchial system which is the main characteristic of obstructive lung disease.

Air Pollutants, Occupational↗
PubMed1995

Cancer of the lung, pleura, larynx and pharynx in an area with an asbestos-cement plant.

Data on persons who died of cancer of the respiratory tract and pharynx in a Croatian coastal area with an asbestos-cement industry were collected and analysed for the period 1970-1990. Cancer mortality data were obtained from the Cancer Registry of Croatia. By the poll method, additional data on occupation, life style (smoking, alcohol drinking), length of residence in the area, educational level and cancer mortality among the relatives were obtained. The results of the investigation showed that the mortality rates for the lung, larynx and pharynx cancers, standardized according to age, were lower in the study area than expected (data for Croatia). Standardized mortality rates for mesothelioma were higher in the area under study for both sexes (except for women in the rural part of the area) than in Croatia. Within the study area the highest mortality rates for follow-up cancers were registered in the settlement where the asbestos-cement plant was located. Some settlements in two municipalities within the area also had higher mortality rates caused by these tumours in comparison with the rest of the study area or Croatia as a whole. In the evaluation of the obtained findings possible uneven distribution of emissions from the asbestos-cement plant caused by prevailing wind and air stream direction were considered.

Air Pollutants, Occupational↗
PubMed1994

Determination of active pellets' position in the selectron-HDR vaginal tube using a therados RFA-3 water phantom system.

The method for determination of the active pellets' position in the Selectron vaginal tube is shown. A special steel cap shielding with narrow window mounted above the Therados RFA-3 semiconductor detector was constructed. By scanning along the Selectron line vaginal tube in air and water, for an appropriate distance with mild dose gradient, the actual active pellets' positions can be determined. The resolution was higher during scanning in the air than in water. The minimum number of tries for checking the whole system depends on the total number of pellet sources in the main safe, and the number of active pellets used. Advantages of this method, compared to other conventional methods for determination of the Selectron-HDR source positions, are associated with high resolution and capability of repetition without movement of the tube during checking procedure.

Brachytherapy↗