Prognostic role of c-met expression in breast cancer patients

Background

Hepatocyte growth factor plays an important role in tumor growth, metastasis and angiogenesis. C-met is HGF''s high affinity receptor.

Aim

The aim of the study was to assess the correlations between c-met expression and clinic-pathological factors in breast cancer tissues. Furthermore, the purpose of the study was to evaluate the prognostic value of the hepatocyte growth factor receptor (HGFR, c-met) expressions in homogenous group of breast cancer patients.

Materials and methods

Tumor samples were collected from 302 patients with breast carcinoma treated with primary surgery. We have assessed the percentage of tumor cells with c-met expression, the intensity of reaction and the ratio of these two factors—immunoreactivity according to the Remmele score.

Results

We have observed no correlations between HGFR immunoreactivities and clinical parameters (tumor size, grade, axillary lymph node status, age). In 5-year observation we have found prognostic value of assessing c-met immunoreactivity in primary tumor.

Conclusion

Our study has revealed prognostic value of c-met. Unlike in other authors’ studies, our patients’ group is very homogenous which might contribute to obtained results.     

Chasing Jenner's vaccine: revisiting cowpox virus classification

Cowpox virus (CPXV) is described as the source of the first vaccine used to prevent the onset and spread of an infectious disease. It is one of the earliest described members of the genus Orthopoxvirus, which includes the viruses that cause smallpox and monkeypox in humans. Both the historic and current literature describe "cowpox" as a disease with a single etiologic agent. Genotypic data presented herein indicate that CPXV is not a single species, but a composite of several (up to 5) species that can infect cows, humans, and other animals. The practice of naming agents after the host in which the resultant disease manifests obfuscates the true taxonomic relationships of "cowpox" isolates. These data support the elevation of as many as four new species within the traditional "cowpox" group and suggest that both wild and modern vaccine strains of Vaccinia virus are most closely related to CPXV of continental Europe rather than the United Kingdom, the homeland of the vaccine.     

Antibody labelling of resilin in energy stores for jumping in plant sucking insects

The rubbery protein resilin appears to form an integral part of the energy storage structures that enable many insects to jump by using a catapult mechanism. In plant sucking bugs that jump (Hemiptera, Auchenorrhyncha), the energy generated by the slow contractions of huge thoracic jumping muscles is stored by bending composite bow-shaped parts of the internal thoracic skeleton. Sudden recoil of these bows powers the rapid and simultaneous movements of both hind legs that in turn propel a jump. Until now, identification of resilin at these storage sites has depended exclusively upon characteristics that may not be specific: its fluorescence when illuminated with specific wavelengths of ultraviolet (UV) light and extinction of that fluorescence at low pH. To consolidate identification we have labelled the cuticular structures involved with an antibody raised against a product of the Drosophila CG15920 gene. This encodes pro-resilin, the first exon of which was expressed in E. coli and used to raise the antibody. We show that in frozen sections from two species, the antibody labels precisely those parts of the metathoracic energy stores that fluoresce under UV illumination. The presence of resilin in these insects is thus now further supported by a molecular criterion that is immunohistochemically specific.     

Role of FSH and triiodothyronine in Sertoli cell development expressed by formation of connexin 43-based gap junctions

Follicle-stimulating hormone (FSH) and triiodothyronine (T3) are known regulatory factors of spermatogenesis initiation. Connexin 43 (Cx43) is the most ubiquitous constitutive protein of gap junctions in the testis. This study evaluates the effects of the hyperstimulation of FSH and T3 during testicular maturation on Cx43 expression in the testis. The newborn, male Wistar rats were divided randomly into four experimental groups: FSH group-daily injections of FSH 7.5?IU/animal; T3 group-100?μg T3/kg body weight; FSH+T3 group-both substances; A control group-received vehicles in the same volume. Proliferating cell nuclear antigen immunohistochemistry and toluidine blue staining were used to determine the germ cell proliferation and degeneration. Cx43 immunolocalization was evaluated to find Cx43 maturational changes. Under FSH treatment, the proliferation rate was high so the total number of Sertoli cells increased with a low level of degeneration and lumen formation. T3 stimulation evoked a reduction in the proliferation rate and a decrease in Sertoli cell number but with intensive formation of lumen. T3+FSH inhibited the proliferation rate and stimulated lumen formation together with degeneration, which negatively influenced the number of germ cells in the seminiferous epithelium. We conclude that T3 action seems to be particularly connected with the maturation of Cx43 gap junctions. FSH stimulates maturation of Sertoli cell function, but this effect may take place regardless of the presence of Cx43-dependent intercellular communication. The hyperstimulation of both FSH and T3 damages Cx43 connections and hence evokes regressional changes in the seminiferous epithelium.     

Effect of salt and osmotic stress on changes in polyamine content and arginine decarboxylase activity in Lupinus luteus seedlings

The effects of NaCl (260 mM) and sorbitol (360 mM) isoosmotic stresses on polyamine titers in lupin (Lupinus luteus L. var. Ventus) in relation to organ-specific responses were investigated. Analysis showed that during the first few hours (4 h) of salt and osmotic stress higher amounts of putrescine (Put) and spermidine (Spd) were accumulated in the roots and leaves of lupin seedlings. After exposing the plants to a longer duration (24 h) of exposure to NaCl, the level of free Put decreased in roots and cotyledons by about 48% and 54%, respectively, and increased in hypocotyls and leaves by about 27% and 73%, respectively. The Level of free Spd also decreased in roots by about 50%, in contrast to the increase of Spd observed in hypocotyls and leaves by about 50% and 70%, respectively. The effect of non-ionic stress on the level of Put and Spd in studied organs of lupin was similar to that of NaCl. Free spermine was at an undetectable level in examined organs. However, in the roots of lupin growing for 24 h in the presence of NaCl and/or sorbitol, the activity of arginine decarboxylase (ADC) (EC 4.1.1.19) increased by about 66% and 80%, respectively. ADC activity in leaves was similar to that observed in the control. Additionally, in the roots and leaves of lupin growing under the stress condition (NaCl or sorbitol), a higher level of polyamines (PAs) bound to microsomal membranes was observed. It is probable that PAs bound to microsomal membranes prevent stress-induced damage. We conclude that both stresses induce biosynthesis of Put and other PAs in the roots, as well as Put accumulation in the leaves, and this may indicate translocation of Put from the roots to the shoot. The possible role of PAs in adaptive mechanisms to stress is discussed.     

Frequency and susceptibility patterns of non-fermenting gram-negative rods isolated from patients hospitalised in intensive care units of a tertiary care hospital

The aim of the study was to assess frequency and susceptibility to antimicrobial agents of non-fermenting gram-negative rods isolated from clinical specimens obtained from patients requiring intensive care, with emphasis on profile of the unit. Identification of cultured isolates was done using automated VITEK and API systems (bioMerieux, France). Susceptibility to antimicrobial agents was tested by a disk-diffusion method according to the NCCLS recommendations. In total the analysis comprised 425 strains of non-fermenting gram-negative rods, constituting 58.9% of all isolates of gram-negative bacteria. In blood cultures predominated strains of A. baumannii (46.8%) and P. aeruginosa (40.4%), while in cultures of other clinical specimens these bacteria comprised 42.9% and 43.9% of isolates. Major differences were observed in frequency of these species on both ICU units. Strains of non-fermenting rods isolated from blood cultures comprised a lower percentage of strains susceptible to antimicrobials (particularly cefepime and carbapenems) than isolates cultured from other specimens. Strains of A. baumannii resistant to imipenem and meropenem were detected with a frequency of 12.5% and 26.7%, respectively. Resistance of P. aeruginosa strains to carbapenems was 62.2% and 44.3%, respectively. There was a relatively high percentage of strains susceptible to cefepime (82.0%), ceftazidime (78.9%), amikacin (77.8%) and piperacillin/tazobactam (69.7%). Conclusions: 1. There was a predominance (58.9%) of strains of gram-negative non-fermenting rods. 2. Isolates from blood cultures were characterised by a much higher percentage of resistant strains in comparison to other specimens. 3. Strains of A. baumannii resistant to carbapenems were recorded. 4. There were differences in frequency and antimicrobial susceptibility among the strains of P. aeruginosa and A. baumannii depending on the type of clinical specimen and ICU profile.     

High levels of circulating interleukin-10 in diabetic nephropathy patients

AIMS: The aim of our study was to analyse the level of circulating interleukin-10 (IL-10) and relate it to the grade of albuminuria in patients with diabetic nephropathy (DN) due to type 1 diabetes mellitus (DM). Since IL-10 has met the criteria for an anti-inflammatory and an immunosuppressive cytokine, its activity may be important for clinical outcome of DN. METHODS: The IL-10 level was measured by ELISA in serum samples from thirty patients with DN due to type 1 DM, and compared with thirty patients with type 1 DM without DN and a control group of thirty, healthy, age- and sex-matched people. RESULTS: We observed a greatly elevated concentration of circulating IL-10 in 30/30 DM patients with DN (mean 140 pg/mL +/- 102), compared to DM patients without DN in whom IL-10 was detectable in only 11/30 patients (0.79 pg/mL +/- 1.24), and the group of healthy people in whom IL-10 was detectable in only 3/30 donors (0.92 pg/mL +/- 0.17). IL-10 appeared to be the strongest independent predictor of albuminuria, followed by HbA1c, diastolic blood pressure and DN duration. There was a positive correlation between the values of IL-10 and albuminuria in DM patients with DN. The patients in the fourth quartile of albuminuria had a distinctly higher concentration of IL-10 than those in the lower quartiles. CONCLUSIONS: The increased concentration of IL-10 in the serum samples from DM patients with DN seems to depend on the severity of the nephropathy. The excessive IL-10 production may indirectly contribute towards DN progression. On the other hand, it may explain the relatively long course of diabetic nephropathy.     

Chemiluminescence of Pholasin caused by peroxynitrite

The kinetics of the oxidation of Pholasin by peroxynitrite, which leads to emission of light, were studied. The reaction shows a lag phase, which is smaller at higher peroxynitrite-to-Pholasin ratios. The total light emission approximately doubles from pH 5 to 9 and decreases precipitously to half the pH 5 value at pH 10. Dioxygen and carbon dioxide accelerate the reaction course, but they do not change significantly the reaction yield. Chemiluminescence of Pholasin is suppressed by antioxidants, but no significant shift is noticed in the time at which light emission is maximal. The chemiluminescence intensity is strongly dependent on the potassium concentration, although it is not significantly affected by lithium, cesium, or magnesium; potassium decreases luminescence. The mechanism of the peroxynitrite-induced oxidation of Pholasin may start with the reversible formation of a protein-peroxynitrite intermediate, or a first oxidation product, followed in subsequent steps by decomposition and light emission. However, many questions concerning the mechanism of the light emission remain to be elucidated.     

Antiradical and anti-H2O2 properties of polyphenolic compounds from an aqueous peppermint extract

Polyphenolic compounds such as eriocitrin, luteolin-7-O-rutinoside, diosmin, hesperidin, narirutin, isorhoifolin, rosmarinic and caffeic acids were identified in an aqueous extract (Ex) obtained from peppermint leaves (Menthae x piperitae folium). The content of polyphenols in Ex was as follows: eriocitrin 38%, luteolin-7-O-rutinoside 3.5%, hesperidin 2.9%, diosmin 0.8%, isorhoifolin 0.6%, narirutin 0.3%, rosmarinic acid 3.7% and caffeic acid 0.05%. The strongest antiradical activity (determined as DPPH* scavenging features) was observed for luteolin-7-O-rutinoside, eriocitrin and rosmarinic acid. Caffeic acid and hesperidin revealed a lower antiradical activity while isorhoifolin, narirutin and diosmin showed the lowest activity. The strongest anti-H2O2 activity was observed for eriocitrin, a little lower for rosmarinic acid. The rate of hydrogen peroxide scavenging activity displayed by luteolin-7-O-rutinoside and caffeic acid was lower than that of rosmarinic acids. Hesperidin appeared to be a very weak scavenger of hydrogen peroxide. Almost no anti-H2O2 activity was demonstrated for diosmin, narirutin and isorhoifolin. Among examined flavonoids, the strongest antiradical and anti-H2O2 activity was shown for compounds with two hydroxy groups bound to the Bring in ortho position in relation to each other. Replacement of one hydroxy group in the Bring with a methoxy group or removing one hydroxy group leads to decrease of antiradical and anti-H2O2 activity of flavonoids. Our results suggest that eriocitrin is a powerful peppermint antioxidant and a free radical scavenger.