PubMed Health⌕ Search

Biomedical subjects

A Link

Publications and source records attributed to A Link.

At least 37 records · Page 2Linked to original sources
PubMed1998

d-Fused [1]benzazepines with selective in vitro antitumor activity: synthesis and structure-activity relationships.

The synthesis of novel quinolino[3,2-d][1]benzazepines and pyrido[3,2-d][1]benzazepines is described. The in vitro antitumor activity of the compounds has been tested in the antitumor screening of the National Cancer Institute (NCI). Several 2,4-diarylpyrido[3, 2-d][1]benzazepin-6-ones and -thiones turned out to exhibit considerable cytotoxicity for tumor cells. For studies of SAR within these series, substituents were introduced into the aromatic rings of the parent systems. Compounds from the thiolactam series tended to show higher potency than the corresponding lactams. Prominent compounds with noteworthy activity and remarkable selectivity for renal cancer cell lines are the lactams 10c, 10g, and 10h and the corresponding thiolactams 11c, 11g, and 11h. Methylation of the azepine nitrogen leads to complete loss of activity, whereas annelation of a triazolo ring at the lactam site or transformation of the thiolactam function to a thiolactim ether results in decreased antitumor activity and selectivity. Consequently, the secondary lactam or thiolactam structure of the seven-membered ring has to be regarded as essential for selective antitumor activity.

Antineoplastic Agents↗
PubMed1998

Transcranial sonographic monitoring during thrombolytic therapy.

Two patients with acute occlusion of the middle cerebral artery (MCA) were treated with intravenous alteplase. Neurovascular monitoring, which was performed simultaneously via transcranial sonography, enabled precise documentation of MCA recanalization. This information was used to tailor the dosage and duration of alteplase treatment. Sonographic information concerning the arterial segments involved in the occlusive process, the actual hemodynamic status, and the collateral blood supply may help to identify those patients most likely to benefit from thrombolysis.

Arterial Occlusive Diseases↗
PubMed1997

Direct analysis of protein mixtures by tandem mass spectrometry.

Methods to identify proteins contained in mixtures are described. The approach uses microcolumn liquid chromatography and automated tandem mass spectrometry in conjunction with protein and nucleotide database searching algorithms. This approach is applied to the identification of proteins obtained by immunoprecipitation reactions, interaction with a GST protein fusion products and interaction with a macromolecular complex.

Chromatography, Liquid↗
PubMed1993

[Vena cava ultrasonography for the assessment of hydration status in kidney insufficiency].

Vena cava diameter (VCD) was measured by ultrasonography in 10 acutely hypervolemic dialysis patients (6 men, 4 women; mean age 61.3 +/- 15.4 years), results being compared with the level of the central venous pressure (CVP) and, in 39 long-term dialysis patients (18 men, 21 women; mean age 56 +/- 15 years), with the plasma concentration of atrial natriuretic peptide (ANP). In 86 subjects without renal disease (43 men, 43 women; mean age 39.4 +/- 14.6 years) there was a statistically highly significant correlation between the end-expiratory VCD and heart rate (r = -0.63; P < 0.001). These data were used to construct a VCD/heart rate (HR) nomogram. In the ten dialysis patients HR-adjusted VCD correlated significantly at various hydration states (54 measurements) with the CVP (r = 0.72; P < 0.001). The steep slope for the relationship between CVP and VCD showed marked interindividual variations. However, in all patients (except one) with a raised CVP (> 12 cm H2O) the HR-adjusted VCD was above the 95th percentile. In the 39 patients on long-term dialysis (13 with, 25 without predialysis tricuspid regurgitation [TR] there occurred a parallel decrease in VCP and ANP during removal of fluid. In the 25 patients without TR, the fall in ANP concentration and VCD correlated significantly (r = 0.70; P < 0.001). These results indicate that, in patients with renal failure but normal cardiac function, measurement of the VCD by ultrasonography provides an adequate index of hydration.

Adult↗
PubMed1991

Inhibition of O6-alkylguanine-DNA alkyltransferase and DNase I activities in vitro by some alkylating substances and antineoplastic agents.

The specificities of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase from brain and liver cells of the chick embryo and of DNase I were demonstrated in vitro by their response to substrate DNA pretreated with monofunctional alkylating agents of different O6-guanine alkylating ability and some antineoplastic agents. Treatment of DNA with ethidium bromide, Hoechst 33258, doxorubicin, Fe2+/bleomycin, and suramin resulted in a dose-dependent diminution of alkyltransferase activity (DE50 approximately 5 micrograms/ml, 15 micrograms/ml, 5 micrograms/ml, 5 micrograms/ml, 100 micrograms/ml, respectively). Apart from bleomycin, comparable results were obtained with DNase I. Thermal denaturation of the substrate DNA reduced both alkyltransferase and DNase I activity. No effect was seen with X-irradiation. Cisplatin decreased only DNase I activity. Some topoisomerase II and/or gyrase inhibitors remained without significant effects on the alkyltransferase reaction whereas DNA catabolism by DNase I was diminished in a dose-dependent manner (DE50 between 6.5 and 19 micrograms/ml).

Alkylating Agents↗
PubMed1987

[Intestinal liberation and resorption of monosaccharides from carbohydrates of different degrees of polymerization. I. Relation between intestinal hydrolysis of carbohydrates and resorption of monosaccharides].

The study was designed to compare the intestinal absorption of monosaccharides from carbohydrates of different chain length. Furthermore, a correlation between the efficiency of hydrolysis of the polymers and the efficiency of the intestinal absorption was expected to be established. Glucose, the disaccharides maltose and sucrose and the polysaccharides maltodextrin DE 20 , maltodextrin DE 5 and starch were employed as substrates. The whole small intestines of anaesthetized rats were perfused in situ for 60 min with 0.5% solutions of these substrates in an open perfusion system. Initially 3-minute fractions of the perfusion medium, later 10-minute fractions were collected. The parameters determined were: secretion of pancreatic alpha-amylase activity, substrate hydrolysis (by alpha-amylase and by disaccharidases of the brush border membrane), intestinal absorption of the monosaccharides. alpha-amylase activity was significantly higher when the perfusion was carried out with starch solution. The possibility is discussed that this high-polymer substrate might stimulate the pancreas to an elevated alpha-amylase secretion. The highest rate of hydrolysis (45 mumol glucose/min) was determined from maltose as a substrate. The cleavage of the high-polymer substrates was less intensive. The hydrolysis of starch was limited by the capacity of the alpha-amylase, that of the sucrose by low activity of the saccharose. Absorption of glucose was more effective from the maltose solution than from the glucose solution. To understand this phenomenon, an additional "hydrolases-related transport system" could be taken into consideration. Glucose absorption from maltodextrin DE 20 was less effective than might have been expected from the rate of hydrolysis. This fact might possibly be explained by an inhibitory effect of oligosaccharides of chain length 4-10, contained in relatively high amounts in maltodextrin DE 20.

Animals↗
PubMedDate not supplied

Polymer-assisted solution-phase synthesis of 2'-amido-2'-deoxyadenosine derivatives targeted at the NAD(+)-binding sites of parasite enzymes.

A polymer-assisted solution-phase (PASP) synthesis of lead structure analogues ready for biological testing without the demand for chromatographic purification is described. Carboxylic acids are coupled to the Kenner or Ellman safety catch linker, respectively, activated by methylation or cyanomethylation and subsequently transferred to the 2'-amino group of the 2'-amino-2'-deoxyadenosine scaffold (5). The chemoselective attack of weakly nucleophilic amino groups on the N-alkylated N-acyl sulfonamide linker allows for the synthesis of amides 6 in high yields without the need for protection of primary and secondary hydroxyl functions. Thus, the use of 4-sulfamylbenzoylaminomethyl polystyrene is reported for the construction of chemoselective polymer-supported acylating reagents instead of its known use as linker in solid-phase peptide or organic synthesis. This approach is demonstrated to be well suited to obtain 2'-amido-2'-deoxyadenosine derivatives 6 in parallel format. Biological evaluation of all compounds reported revealed no improvement over known lead structures.

Animals↗