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Biomedical subjects

R Laskowski

Publications and source records attributed to R Laskowski.

At least 19 recordsLinked to original sources

Frequency of three BRCA1 gene founder mutations in breast/ovarian cancer families from the Pomerania-Kujawy region of Poland.

A group of 63 families from the Pomerania-Kujawy region were analyzed for three BRCA1 gene Polish founder mutations, 5382insC, 300T>G, and 4153delA, because of breast (BrCa) and/or ovarian cancer (OvCa) history. The analysis was carried out by multiplex polymerase chain reaction method. BRCA1 mutation was revealed in nine (14%) families: in three (33%) of hereditary BrCa and OvCa families, in three (8%) of hereditary BrCa families, and in three (21%) of hereditary OvCa families. According to risk criteria, it was revealed in 45% of high-risk families with more than three cancers, 13% of moderate-risk families with two cancers, and 8% of families with sporadic OvCa. In six families, the mutation was found in a proband with BrCa or OvCa and in three families, the mutation was found in a healthy proband, first-degree relative of a patient deceased of BrCa or OvCa. 5382insC frameshift mutation accounted for 67% and 300T>G missense mutation for 33% of all identified familial mutations. 4153delA frameshift mutation was not found in analyzed sample of families. 5382insC mutation was found in 9% and 300T>G in 5% of all investigated families, and in 27 and 18%, respectively, of high-risk families. This underlines the importance of applying strict inclusion criteria to analyze mutation frequency in hereditary BrCa/OvCa families.

Breast Neoplasms↗

Increased adaptability of young judo sportsmen after protein supplementation.

AIM: The purpose of this study was to examine the effects of protein supplementation on adaptation process in young judoists. The assumption of this study was that young sportsmen would benefit from the protein supplements because of increased demand due to growth and training. METHODS: Twelve judoists were divided into two groups. One group received a soy protein supplement 0.5 g/kg body mass/day (P) and the second group (C) did not. Before and after 4 weeks of training the maximum oxygen uptake (VO(2max)) was evaluated in both groups. In addition, they performed Wingate test, where the maximal power output and the total work output were measured. RESULTS: The obtained results indicate that after 4 weeks of judo training the VO(2max) increase and Wingate test performance significantly improves. In both cases the increase was much higher in judoists who received the protein supplement, comparing to the control group. When the judoist were trained for another 3 months but without the protein supplementation, we observed disappearance of the differences in VO(2max) between the two studied groups. CONCLUSION: These data clearly indicate that the supplementation of a normal diet with soy protein (0.5 g per kg of body mass) is beneficial for a judoist. An increase in aerobic and anaerobic performance is higher in the protein supplemented group, despite the fact that the training protocol is the same for all the athletes. We conclude that it is possible to increase the adaptation to judo training by protein supplementation.

Adaptation, Physiological↗

Streptococcus pneumonia YlxR at 1.35 A shows a putative new fold.

The structure of the YlxR protein of unknown function from Streptococcus pneumonia was determined to 1.35 A. YlxR is expressed from the nusA/infB operon in bacteria and belongs to a small protein family (COG2740) that shares a conserved sequence motif GRGA(Y/W). The family shows no significant amino-acid sequence similarity with other proteins. Three-wavelength diffraction MAD data were collected to 1.7 A from orthorhombic crystals using synchrotron radiation and the structure was determined using a semi-automated approach. The YlxR structure resembles a two-layer alpha/beta sandwich with the overall shape of a cylinder and shows no structural homology to proteins of known structure. Structural analysis revealed that the YlxR structure represents a new protein fold that belongs to the alpha-beta plait superfamily. The distribution of the electrostatic surface potential shows a large positively charged patch on one side of the protein, a feature often found in nucleic acid-binding proteins. Three sulfate ions bind to this positively charged surface. Analysis of potential binding sites uncovered several substantial clefts, with the largest spanning 3/4 of the protein. A similar distribution of binding sites and a large sharply bent cleft are observed in RNA-binding proteins that are unrelated in sequence and structure. It is proposed that YlxR is an RNA-binding protein.

Amino Acid Sequence↗

Time to death response in carabid beetles exposed to multiple stressors along a gradient of heavy metal pollution.

We investigated the responses of invertebrates inhabiting polluted environments to multiple stressors. Carabid beetles (Pterostichus oblongopunctatus F.) were subjected to food deprivation and insecticide treatment (dimethoate) to resolve trends associated with a gradient of heavy metal pollution. Metal concentrations along the gradient of five sites ranged from approximately 150 to 10,500 mg/kg Zn, 136 to 2600 mg/kg Pb, and 0.84 to 81.9 mg/kg Cd. There was no difference in body mass along the pollution gradient. However, the beetles originating from the most contaminated sites were significantly less tolerant to food deprivation than beetles from the reference site. Median survival time was 120 h for the two most polluted sites, compared with 168 h at the reference site. Beetles from the two most polluted sites were also significantly more susceptible to dimethoate at 0.1 microgram active ingredient/beetle. Median survival times were 12 and 123 h for beetles from the two most polluted sites and 359 h for the reference site. Carabid beetles exposed to chronic pollution, therefore, exhibit elevated susceptibility to additional stressors.

Adaptation, Physiological↗

Susceptibility of Canadian isolates of Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae to oral antimicrobial agents.

We measured the susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae) to several currently approved antimicrobial agents by two different methods. We also measured the susceptibility of isolates to seven fluoroquinolones. Beta-lactamase was produced by 123/566 (21.7%) of H. influenzae isolates compared with 178/200 (89%) of M. catarrhalis isolates. For S. pneumoniae 83/374 (22.2%) isolates were penicillin resistant and of these 2.1% (8/374) showed high level resistance (MIC > or = 2 mg/l). Regardless of methodology, all fluoroquinolones were highly active against H. influenzae (MIC(90) < or = 0.031 mg/l) and M. catarrhalis (MIC(90) < or = 0.064 mg/l) isolates. Susceptibility of H. influenzae to cefuroxime and amoxycillin/clavulanic acid was 99-100% whereas 84-85.5% were susceptible to cefaclor and cefprozil. Azithromycin susceptibility ranged from 82.6 to 99.2% depending on the method. M. catarrhalis isolates were uniformly susceptible to all agents tested except amoxycillin. Cross-resistance in S. pneumoniae to all non-quinolone agents was concurrent with increasing penicillin resistance as shown by increasing MIC90 values. For the fluoroquinolones tested, the rank order of potency based on MIC(90) values was as follows: gemifloxacin (0.031-0.063 mg/l), trovafloxacin (0.125 mg/l), moxifloxacin (0.125-0.25 mg/l), grepafloxacin (0.125-0.25 mg/l), gatifloxacin (0.5 mg/l), levofloxacin (1 mg/l) and ciprofloxacin (2 mg/l). Our study confirms either a high or increasing prevalence of antimicrobial resistant respiratory pathogens in Canada and also compares the new and old fluoroquinolones and their potential role as therapy for community-acquired infections. The prevalence of beta-lactamase positive H. influenzae may have decreased from levels reported in previous studies.

Administration, Oral↗

Why short-term bioassays are not meaningful--effects of a pesticide (Imidacloprid) and a metal (cadmium) on pea aphids (Acyrthosiphon pisum Harris).

The life-table study on effects of a heavy metal, Cd (100 and 200 mg kg-1 soil), and an insecticide, imidacloprid (4 and 40 g a.i. ha-1), on pea aphids revealed significant effects of both chemicals on life history traits and population dynamics. Substantial differences in the action of the two chemicals and between the two doses of imidacloprid were observed. The pesticide caused high mortality at the beginning of the experiment, however some aphids were able to live for as long as control insects. In contrast, Cd-induced mortality was low at the beginning but increased during the experiment. Analysis of data collected during the first 10 days of the experiment, the first 20 days, or for the whole life-time of the cohort gave different results. While highly significant effects of imidacloprid were detected already after 10 days of the experiment, Cd treatment resulted in no effect for this time of exposure. Higher dose of imidacloprid decreased growth and development rates along with delayed reproduction (9th or 10th day). In contrast, the aphids treated with the low dose of imidacloprid and with both concentrations of Cd started their reproduction at the same day as untreated insects (6th or 7th day), but the reproduction tended to cease earlier. This indicates that too short ecotoxicological tests may result in serious underestimation of some effects, while overestimating others.

Animals↗

Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms.

Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin are fluoroquinolones with enhanced Gram-positive activity while retaining broad-spectrum activity against Gram-negative pathogens. Levofloxacin and ciprofloxacin are older quinolones with broad activity against Gram-negative pathogens and borderline activity against some Gram-positive organisms. We compared the in vitro activity of these compounds against 4151 Gram-negative and -positive organisms. Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin were highly active against penicillin sensitive and resistant Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus agalactiae. Ciprofloxacin and levofloxacin were active but less potent. All compounds were highly active (overall) against Gram-negative pathogens with ciprofloxacin being the most active agent against Pseudomonas aeruginosa. Our data indicate that the advanced fluoroquinolones will be important compounds for treating infections caused by Gram-positive and Gram-negative pathogens.

Anti-Infective Agents↗

In-vitro activity of cefepime and seven other antimicrobial agents against 1518 non-fermentative Gram-negative bacilli collected from 48 Canadian health care facilities. Canadian Afermenter Study Group.

Non-fermentative bacilli are primarily nosocomial pathogens, and are also often resistant in vitro to a broad range of antimicrobial agents. In this large Canadian study, we collected 1466 clinical, non-repeat isolates of Pseudomonas aeruginosa, 21 of Acinetobacter spp. and 31 Stenotrophomas maltophilia. MICs of eight antibiotics were determined by the NCCLS microdilution method in a central laboratory. Tobramycin was the most active agent against P. aeruginosa (94.5% susceptible); amikacin and imipenem were the most active against Acetinobacter spp. (100%) and ceftazidime was the most active against S. maltophilia (40.6%). Against each group of isolates, cefepime was active against 87, 86.4 and 15.6%, respectively. This in-vitro study showed that cefepime may be a useful additional agent in the treatment of infections caused by P. aeruginosa and Acinetobacter spp., but not when S. maltophilia is considered pathogenic.

Anti-Bacterial Agents↗

Effect of heavy metals and storage time on two types of forest litter: basal respiration rate and exchangeable metals.

Two types of forest litter, MOR and MULL, were treated with 0 (control), 25, 100, 400, 1600, and 6400 mg kg-1 Cd, Cu, Pb, or Zn after different storage times (35, 75, and 125 days at approx 5 degreesC). Highly significant effects on respiration rate were observed for dose of heavy metals, type of litter, type of metal, and storage time. The respiration rate of untreated MULL litter was lower than that of untreated MOR in all incubations, and the slope of the relation to the dose of metals was steeper for MOR. Respiration rates after storage were lower than in fresh litter, and the slope of the relation between respiration rate and metal dose was less steep after storage. In the first incubation, MULL litter was more sensitive to Cd, Cu, and Pb and less sensitive to Zn than MOR litter. After 125 days of storage, no single significant effect was found in MULL litter, whereas in MOR litter all metals still inhibited respiration rate significantly. The relative toxicity of metals was similar for both litter types, and the average EC50respiration values were (mg kg-1) Cu=3880, Zn=5610, Cd=6320, and Pb=24800. The percentages of exchangeable metals (1 M NH4OAc, pH=7) in MULL litter were lower on average than in MOR litter, and the order of solubility of the metals was Cd>Zn>Pb>Cu. Storage caused no significant difference in the average percentage of exchangeable metal. The highest doses of heavy metals increased the amounts of Ca, K, Mg, and Na extracted.

Cadmium↗

Heat shock proteins (HSP70) as biomarkers in ecotoxicological studies.

Hsp70, so-called stress proteins, were studied in the centipede Lithobius mutabilis when exposed in laboratory tests to different concentrations of the insecticide dimethoate (DMT; 0, 0.012, 0.111 mg kg-1 dwt), the detergent linear alkilobenzene sulfonate (LAS; 0, 16, 80, 400, 2000, 10,000 mg kg-1 dwt), and copper (Cu; 0, 56, 167, 500, 1000, 1500 mg kg-1 dwt) and in the field in captured animals from polluted (2 and 4 km from a zinc-and-lead smelter) and unpolluted (35 and 40 km from the smelter) areas. Hsp70 in centipedes were also tested for seasonal differences (March and September) in field-captured animals and for a temperature effect under laboratory conditions (5, 15, and 25 degrees C). Moreover, hsp70 were examined in housefly (Musca domestica) pupae after rearing larvae on food medium contaminated with DMT or LAS. Hsp70 were found in all animals tested, including controls, and their levels were not clearly related to the laboratory treatment with chemicals or temperature or to the degree of contamination in polluted areas. In centipedes from unpolluted areas, a significant seasonal difference in hsp70 content was found. The problems with using hsp70 as a universal biomarker in ecotoxicological studies are discussed.

Animals↗

Effect of Zn, Cu, Pb, and Cd on fitness in snails (Helix aspersa).

Juveniles and adults of the Brown garden snail (Helix aspersa Müll.) were fed on an artificial diet contaminated with Zn (ca. 40-12,000 micrograms.g-1 dry wt), Cu (ca. 9-1600 micrograms.g-1 dry wt), pb (ca. 0.4-12,700 micrograms.g-1 dry wt), Cd (ca. 0.16-145 micrograms.g-1 dry wt), and all four metals mixed together for 120 days. Significant negative exponential regressions of food consumption and fecundity on concentrations were found for all treatments. Growth rate was affected significantly only by Zn and mixed treatments. The calculated EC20(consumption) values for juveniles were (in microgram.g1): Zn, 855; Cu, 248; Pb, 5290; Cd, 60; and for adults: Zn, 1240; Cu, 275; Pb, 3120; Cd, 147. In mixed treatment EC20(consumption) values were substantially lower indicating the additive effect of pollution with these four metals. EC20(consumption) for Zn in mixed treatment was 329 micrograms.g-1 for juveniles and 661 micrograms.g-1 for adults. The following EC20 values were estimated for fecundity (in micrograms.g-1): Zn, 1740; Cu, 533; Pb, 6140; Cd, 120; Zn in mixed treatment, 2210. The relative toxicities of the four metals were compared with their ratios in contaminated field sites. Comparing Zn and Cd, for example, even though Zn is ca. 13-24 times less toxic than Cd, it is usually present in plants and forest litter in concentrations ca. 100 times greater than those of Cd. Thus, of these two metals, Zn appeared to be potentially the most important pollutant in ecologically relevant situations. No effect of any treatment on mortality was found during the 4-month experiment. The calculated scenarios of population dynamics under the stress of chronic pollution with mixtures of the four metals revealed that the delayed reproduction due to estivation of snails may be the main cause of population decline at high metal concentrations in food. However, at concentrations at and below ca. 1000 micrograms Zn.g-1 in food, if the reproduction is not delayed the population may persist for a long time (0.25 control number after 50 years).

Aging↗

Accumulation of Zn, Cu, Pb and Cd in the garden snail (Helix aspersa): implications for predators.

Accumulation of Zn, Cu, Pb and Cd was studied in snails fed for 120 days on diets contaminated with each metal separately and with all metals mixed together. The concentrations of Zn in food were in the range 39 to 12 200 mg kg(-1), Cu 9-1640 mg kg(-1), Pb 0.4-12 700 mg kg(-1), and Cd 0.16-146 mg kg(-1) on a dry weight basis. At the highest concentrations of all metals the consumption rates decreased significantly. For the remaining concentrations, Zn and Cu were accumulated in soft tissue in proportion to their concentrations in food. The lowest treatments of Pb and Cd did not cause any increase in soft tissue concentrations of these metals but at average treatments, a clear increase was observed. Copper was accumulated especially efficiently, exceeding concentrations in food throughout the whole range of treatments. Except for the lower end of experimental treatments, Zn was accumulated approximately in direct proportion to its concentration in the diet. Lead was the most efficiently regulated metal, with soft tissue concentrations always substantially lower than in food. Approximately 60% of Zn, 90% of Cu, 43% of Pb and 68% of Cd on average was assimilated from food. The assimilation efficiency of food alone was ca 74%. The concentrations of metals in shells increased significantly with exposure, but (with one exception) the concentrations in shells did not exceed 5% of those found in soft tissue. We argue that snails are more important as agents of food-chain transport of Cu and Cd, than of Zn or Pb. Our results indicate also that snails are not able to deposit significant quantities of metals in their shells, at least during the time scale of our laboratory experiment.

Journal Article↗

Effect of heavy metals and mineral nutrients on forest litter respiration rate.

Two hypotheses were tested: (1) heavy metals such as Zn, Pb and Cd can suppress the respiration rate of forest litter at low-moderate pollution levels, and (2) mineral nutrients such as K, Ca and Mg can counteract the toxicity of heavy metals when applied onto the polluted litter. In a completely randomised design, three doses of heavy metals were used: Cd-10, 50, 250; Pb-100, 500, 2500; Zn-200, 1000, 5000 microg/g dwt litter, respectively. For Ca, Mg and K, the doses corresponded to 100, 500 and 2500 microg/g. A significant decrease in cumulated CO2 evolution after 4 weeks of incubation was found for the litter samples treated with medium doses of Zn, Cd/Ca, Cd/Mg, Pb/Ca, Pb/Mg, Pb/K, Zn/Mg, Zn/Ca, Zn/K and for all the highest-dose treatments. The largest drop in respiration rate in both the medium and the highest doses was caused by additions of Zn either alone or in combination with K, Ca or Mg. The additions of mineral nutrients were found to decrease the litter respiration rate below the value measured for the respective heavy metal alone in the case of Cd/Ca, Cd/Mg, Pb/Ca, Pb/Mg and Pb/K in the medium-dose treatments, and for Cd/Ca, Cd/Mg, Cd/K, Pb/Ca and Pb/Mg in the highest-dose treatments. In all other cases, additions of the mineral nutrients did not influence the respiration rate significantly when compared to the effect of the respective heavy metal.

Journal Article↗