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Biomedical subjects

A Anton

Publications and source records attributed to A Anton.

At least 19 recordsLinked to original sources
PubMed2005

Regulation of mesenchymal stem cell and chondrocyte differentiation by MIA.

Melanoma inhibitory activity (MIA), also referred to as cartilage-derived retinoic acid-sensitive protein (CD-RAP), an 11-kDa secreted protein, is mainly expressed in cartilaginous tissue during embryogenesis and adulthood. Currently, the function of MIA in cartilage tissue is not understood. Here, we describe that MIA acts as a chemotactic factor on the mesenchymal stem cell line C3H10T1/2, stimulating cell migration significantly at concentrations from 0.24 to 240 ng/ml, while inhibiting cell migration at higher doses of 2.4 microg/ml. When analyzing the role of MIA during differentiation processes, we show that MIA by itself is not capable to induce the differentiation of murine or human mesenchymal stem cells. However, MIA influences the action of bone morphogenetic protein (BMP)-2 and transforming growth factor (TGF)-beta 3 during mesenchymal stem cell differentiation, supporting the chondrogenic phenotype while inhibiting osteogenic differentiation. Quantitative RT-PCR analysis revealed the up-regulation of the cartilage markers MIA, collagen type II and aggrecan in human mesenchymal stem cell (HMSC) cultures differentiated in the presence of MIA and TGF-beta 3 or BMP-2 when compared to HMSC cultures differentiated in the presence of TGF-beta 3 or BMP-2 alone. Further, MIA down-regulates gene expression of osteopontin and osteocalcin in BMP-2 treated HMSC cultures inhibiting the osteogenic potential of BMP-2. In the case of human primary chondrocytes MIA stimulates extracellular matrix deposition, increasing the glycosaminoglycan content. Therefore, we postulate that MIA is an important regulator during chondrogenic differentiation and maintenance of cartilage.

Adult↗
PubMed2001

Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study.

PURPOSE: To determine the relative efficacy of a cyclophosphamide epirubicin and fluorouracil (CEF) regimen compared with an intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in metastatic breast cancer. PATIENTS AND METHODS: Patients were randomized to receive either CEF (cyclophosphamide 400 mg/m(2) IV, epirubicin 50 mg/m(2) IV, and fluorouracil 500 mg/m(2) IV on days 1 and 8), or CMF (cyclophosphamide 500 mg/m(2) IV, methotrexate 40 mg/m(2) IV, and fluorouracil 600 mg/m(2) IV on days 1 and 8). Treatment was given in 3- to 4-week cycles for a total of six to nine cycles. RESULTS: A total of 460 patients (223 CEF and 237 CMF) were randomized. Overall response rate was superior for CEF than CMF in all randomized patients (57% v 46%, respectively; P =.01) and in the assessable subset (66% v 52%, respectively; P =.005). With a median follow-up of more than 20 months, time to progression (TTP) was significantly longer with CEF than CMF (median 8.9 v 6.3 months, respectively; P =.0064), as was time to treatment failure (TTF) (median 6.2 v 5.0 months, respectively; P =.01). Significant survival differences were not observed between CEF and CMF (median 20.1 v 18.2 months, respectively; P =.23). Granulocytopenia and infections were similar in both arms. Grade 3/4 nausea/vomiting and alopecia were more frequent with CEF, whereas diarrhea was more frequent with CMF. Cardiac toxicity, primarily asymptomatic, required withdrawal from study of 15 patients on CEF (7%) and one patient on CMF. CONCLUSION: This CEF regimen safely provides significantly better tumor control than CMF, manifest as a higher response rate, and longer TTP and TTF, but not survival, when used as first-line chemotherapy for metastatic breast cancer.

Adult↗
PubMed2000

Efficient charge separation in C60-based dyads: triazolino

Triazoline[4,5][60]fullerenes are strong electron acceptors that form with tetrathiafulvalene (TTF), a novel type of donor-acceptor dyad exhibiting efficient improved electron-transfer dynamics. In particular, a rapid photoinduced intramolecular electron transfer, forming a charge-separated state, is followed by a slow charge recombination to generate the fullerene triplet excited state in moderate quantum yields.

Journal Article↗
PubMed1999

Sertoli cells enhance the survival of co-transplanted dopamine neurons.

One of the major issues in neural transplantation is the low survival rate (<5%) of transplanted dopamine (DA) neurons [3]. Recently it has been shown that it is possible to enhance the survival of these neurons, which in turn may decrease the amount of tissue that is required for each transplantation patient. The present paper demonstrates a novel approach for enhancing neuronal survival by co-transplantation of neuronal tissue with Testis-derived Sertoli cells (SC). This strategy could improve neuronal survival through the provision of trophic support.

Animals↗
PubMed1999

Increasing dose intensity of cisplatin-etoposide in advanced nonsmall cell lung carcinoma: a phase III randomized trial of the Spanish Lung Cancer Group.

BACKGROUND: The authors designed this randomized, controlled trial to assess whether dose intensification of a cisplatin-etoposide combination (PE), achieved by shortening the interval between chemotherapy cycles, would improve response rate and survival. The maximum tolerated dose of PE was administered in either 3- or 4-week cycles to patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS: One hundred twenty-three patients were randomized into two groups. The dose-intense arm received cisplatin 35 mg/m2 and etoposide 200 mg/m2 on Days 1-3 every 4 weeks. The dose-dense arm received the same schedule every 3 weeks along with 5 microg/kg of recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) administered subcutaneously on Days 4-13. RESULTS: Patient characteristics were well balanced in both treatment arms. Fifty-four percent of patients were classified as Stage IIIB. A 32% increase in relative dose intensity was achieved in the dose-dense arm compared with the dose-intense arm. The response rates were 32% in the dose-intense arm and 27% in the dose-dense arm (P = 0.9). The median overall survival was higher in the dose-dense arm, 9 versus 7.2 months (P = 0.2). The main toxicity was myelosuppression, although the administration of GM-CSF significantly reduced the percentage of patients with Grade 4 granulocytopenia (53% vs. 78%). Fifty-four percent of the patients in the dose-intense arm and 35% of those in the dose-dense arm developed febrile neutropenia (P = 0.07). There were ten (8%) treatment-related deaths, three (4%) in the dose-intense arm and seven (12%) in the dose-dense arm (P = 0.3); three deaths in each arm were due to febrile neutropenia. CONCLUSIONS: The dose-intensification achieved in the dose-dense PE regimen did not correlate with significant improvements in response rate or survival and cannot be recommended in the light of the diversity of new drug combinations available today. However, the use of rhGM-CSF significantly reduced the incidence of severe granulocytopenia.

Adult↗
PubMed1999

CzcD is a heavy metal ion transporter involved in regulation of heavy metal resistance in Ralstonia sp. strain CH34.

The Czc system of Ralstonia sp. strain CH34 mediates resistance to cobalt, zinc, and cadmium through ion efflux catalyzed by the CzcCB(2)A cation-proton antiporter. The CzcD protein is involved in the regulation of the Czc system. It is a membrane-bound protein with at least four transmembrane alpha-helices and is a member of a subfamily of the cation diffusion facilitator (CDF) protein family, which occurs in all three domains of life. The deletion of czcD in a Ralstonia sp. led to partially constitutive expression of the Czc system due to an increased transcription of the structural czcCBA genes, both in the absence and presence of inducers. The czcD deletion could be fully complemented in trans by CzcD and two other CDF proteins from Saccharomyces cerevisiae, ZRC1p and COT1p. All three proteins mediated a small but significant resistance to cobalt, zinc, and cadmium in Ralstonia, and this resistance was based on a reduced accumulation of the cations. Thus, CzcD appeared to repress the Czc system by an export of the inducing cations.

Bacterial Proteins↗
PubMed1999

Transcriptional organization of the czc heavy-metal homeostasis determinant from Alcaligenes eutrophus.

The Czc system of Alcaligenes eutrophus mediates resistance to cobalt, zinc, and cadmium through ion efflux catalyzed by the CzcCB2A cation-proton antiporter. DNA sequencing of the region upstream of the czcNICBADRS determinant located on megaplasmid pMOL30 revealed the 5' end of czcN and a gene for a MgtC-like protein which is transcribed in the orientation opposite that of czc. Additional open reading frames upstream of czc had no homologs in the current databases. Using oligonucleotide-probed Northern blotting experiments, a 500-nucleotide czcN message and a 400-nucleotide czcI message were found, and the presence of 6, 200-nucleotide czcCBA message (D. Van der Lelie et al., Mol. Microbiol. 23:493-503, 1997) was confirmed. Induction of czcN, czcI, czcCBA, and czcDRS followed a similar pattern: transcription was induced best by 300 microM zinc, less by 300 microM cobalt, and only slightly by 300 microM cadmium. Reverse transcription-PCR gave evidence for additional continuous transcription from czcN to czcC and from czcD to czcS, but not between czcA and czcD nor between czcS and a 131-amino-acid open reading frame following czcS. The CzcR putative response regulator was purified and shown to bind in the 5' region of czcN. A reporter strain carrying a czcNIC-lacZ-czcBADRS determinant on plasmid pMOL30 was constructed, as were DeltaczcR and DeltaczcS mutants of this strain and of AE128(pMOL30) wild type. Experiments on (i) growth of these strains in liquid culture containing 5 mM Zn2+, (ii) induction of the beta-galactosidase in the reporter strains by zinc, cobalt, and cadmium, and (iii) cDNA analysis of czcCBA mRNA synthesis under inducing and noninducing conditions showed that the CzcRS two-component regulatory system is involved in Czc regulation.

Alcaligenes↗
PubMed1998

Patterns of optic disk damage in patients with early focal visual field loss.

PURPOSE: To study the patterns of structural damage of the optic disk in patients with early focal visual field loss using a confocal scanning laser ophthalmoscope. METHODS: Thirty-nine subjects with repeatable early focal visual field loss were included. The Heidelberg Retina Tomograph (Heidelberg Engineering, Heidelberg, Germany) was used to obtain topographic optic disk measurements. For analysis of structural damage, the topographic measurements were divided into 36 10-degree sectors. Sector analysis was performed using sector rim area to sector disk area ratio. Patients were assigned to one of three groups based on the measurement of the optic disk damage: (1) diffuse disk damage; (2) focal disk damage; or (3) no detectable disk damage. RESULTS: Approximately half of the patients with early focal glaucomatous visual field loss showed diffuse optic disk damage, one quarter to one third had focal damage, and one sixth had no detectable damage. Optic disk area was smallest in the no-detectable-damage group (1.71 + 0.19 mm2), followed by the focal-damage group (2.06 + 0.54 mm2), and was largest in the diffuse damage group (2.29 + 0.48 mm2; P = .22). CONCLUSION: In patients with early focal glaucomatous visual field loss, observable optic disk damage can be diffuse, focal, or undetectable. The Heidelberg Retina Tomograph may be capable of detecting different patterns of diffuse or focal structural damage.

Adult↗
PubMed1998

Mapping structural to functional damage in glaucoma with standard automated perimetry and confocal scanning laser ophthalmoscopy.

PURPOSE: To develop a quantitative method for analysis of the topographic relationship between structural and functional damage in patients with glaucoma. METHODS: We studied 26 patients with primary open-angle glaucoma, focal optic disk damage, and focal visual field loss. The visual field was evaluated with automated perimetry, and the optic disk topography was assessed with a confocal scanning laser ophthalmoscope. Topographic measurements were calculated in 10-degree sectors and compared with a normative database (n=52). The topographic relationship of structural damage and functional loss was analyzed. RESULTS: Rim area ratio was defined as the ratio of rim area in each 10-degree sector divided by the total rim area. This ratio resulted in the identification of one (46%) or more (54%) clusters of optic disk sectors as outside normal limits in all 26 patients (12 and 14 patients, respectively). Twenty-two patients (84%) with superior hemifield sensitivity loss tended to have inferior rim defects, and vice versa. Nasal visual field defects close to the horizontal midline were matched with damaged rim areas close to the vertical midline. CONCLUSIONS: This mapping method allows an objective and quantitative evaluation of the optic disk and visual field in patients with glaucoma and focal damage. Although the topographic relationship between structure and function is characterized by considerable interindividual variability, the identification of certain patterns may be useful to aid in the evaluation of glaucomatous damage.

Adult↗
PubMed1997

Nerve fiber layer measurements with scanning laser polarimetry in ocular hypertension.

OBJECTIVE: To measure and compare scanning laser polarimeter measurements of the nerve fiber layer in normal subjects and in patients with ocular hypertension (OHT). METHODS: Scanning laser polarimetry was performed in 39 normal subjects and 39 age-matched patients with OHT. One eye of each patient was randomly selected for the study. For each eye, a mean retardation map was calculated from 3 separate scans of 65536 individual retinal locations (256 x 256 pixels). Retardation measurements within a 10-pixel-wide band located concentrically with the disc margin at 1.7-disc diameters were evaluated. RESULTS: Mean (+/-SD) retardation (in degrees) was significantly higher (P = .03) in normal subjects (10.4 +/- 1.5 degrees) than in patients with OHT (9.7 +/- 1.0 degrees). In the inferior retina, mean +/-SD retardation was higher (P = .03) in normal subjects (10.8 +/- 1.7 degrees) than in patients with OHT (10.1 +/- 1.0 degrees). In the superior retina, mean +/-SD retardation also was higher in normal subjects (9.8 +/- 1.6 degrees) than in patients with OHT (9.3 +/- 1.2 degrees), although the difference was not statistically significant (P = .19). Retardation measurements for 3 of eight 45 degrees sectors around the disc were significantly higher in normal subjects than in patients with OHT. CONCLUSION: Retardation measurements with the scanning laser polarimeter were significantly lower in patients with OHT than in normal subjects.

Adult↗
PubMed1997

Mapping structural damage of the optic disk to visual field defect in glaucoma.

PURPOSE: To evaluate the relation between the location of focal visual field defects and optic disk damage in eyes with glaucoma by short-wavelength automated perimetery and confocal scanning laser ophthalmoscopy. METHODS: In 14 patients (14 eyes) with open-angle glaucoma, focal optic disk damage, and focal visual field loss, we obtain visual fields with short-wave-length automated perimetry. The short-wavelength automated perimetry visual field was divided into 21 zones, representing retinal nerve fiber layer arcuate bundles. Test points were compared with a normative database. The optic disk was assessed with a confocal scanning laser ophthalmoscope. Optic disk measurements were calculated in 10-degree sectors and compared with a normative database using a new measure, the rim area ratio, which adjusts for individual differences in disk size. RESULTS: The mean number (+/-SD) of damaged visual field zones was 3.9 (+/-1.9), and the mean number of damaged rim sectors was 5.0 (+/-2.9). Focal defects on the optic disk and on short-wavelength automated perimetry were topographically related with specific damaged visual field zones corresponding to specific damaged rim sectors. CONCLUSIONS: In patients with open-angle glaucoma with focal optic disk damage and focal visual field loss, defects in optic disk and short-wavelength automated perimetry are topographically related. The rim area ratio can be used to identify focal optic nerve defects.

Adult↗
PubMed1994

Effects of environmental factors and Mn, Zn, Cu trace elements on the soil phosphomonoesterase and amidase activity. Application of DISITOBI model.

A soil incubation experiment was carried out in a complex experimental system to simulate the effect of environmental factors and 3 trace elements on the phosphomonoesterase and amidase activity of 2 soils. DISITOBI model assures information about experimental object characterized by multidimensional response-function. Plant residue+mineral nitrogen addition increased phosphomonoesterase activity of investigated soils through its effect on enzyme synthesis. A significant part of the increase in phosphomonoesterase activity is the result of the exogenous enzyme input of plant residues. Mineral phosphorus addition reduced the activity after 16 days incubation under our experimental conditions. Plant residue+mineral nitrogen addition reduced amidase activity of chernozem soil presumably due to ammonium and nitrate inhibiting soil amidases.

Amidohydrolases↗
PubMed1994

Effect of carbon- and phosphorus-content on the phosphomonoesterase activity in soil.

The root weight of plants grown in the soil increases its phosphomonoesterase activity. This effect is decreasing with time. The effect of soil organic matter content is similar to that of the root, but this is increasing with time. The latter phenomenon is connected with the progress of humification. The inhibitory effect of soluble phosphate on the phosphomonoesterase activity is shown to be significant only after 120 days incubation and can be pointed out only with multiple regression analysis.

Carbon↗
PubMed1992

Heavy ion induced double strand breaks in bacteria and bacteriophages.

DNA damage induced by heavy ions in bacterial cells and bacteriophages such as Bacillus subtilis, E. coli and Bacteriophage T1 were investigated by analyzing the double strand breaks in the chromosomal DNA. This kind of lesion is considered as one of the main reasons for lethal events. To analyze double strand breaks in long molecules of DNA--up to some Mbp in length--the technique of pulse field agarose gel electrophoresis has been used. This allows the detection of one double strand break per genome. Cell lysis and DNA isolation were performed in small agarose blocks directly. This procedure secured minimum DNA destruction by shearing forces. After running a gel, the DNA was stained with ethidium bromide. The light intensity of ethidium bromide fluorescence for both the outcoming (running) DNA and the remaining intact DNA were measured by scanning. The mean number of double strand breaks was calculated by determining the quotient of these intensities. Strand break induction after heavy ion and X-ray irradiation was compared.

Argon↗
PubMed1992

Etoposide (E) + epirubicin (E) + cisplatin (P) combination chemotherapy (EEP) in advanced gastric cancer: negative impact on clinical outcome. Spanish Cooperative Group for GI Tumor Therapy (T.T.D.).

One hundred nineteen patients with advanced gastric cancer were included in a study comparing EEP vs. FEM chemotherapy. The response rate was higher (30%) in patients on EEP than in those treated with FEM (p = 0.05). Severe leukopenia, anemia, alopecia and infection were significantly more frequent on EEP. In addition, because of its intrinsic toxicity, EEP chemotherapy has a negative impact on the performance status of patients treated with this regimen, more than half of whom presented at least one episode of severe symptomatic toxicity while on EEP chemotherapy. The median time to progression and median survival for EEP-FEM were 2.08-3.4 and 4.2-7.9 months, respectively. Our data do not support the use of EEP chemotherapy in patients with AGC.

Antineoplastic Combined Chemotherapy Protocols↗