Marfan syndrome: Absence of type I or III collagen structural defects in 25 patients

Summary The structure and metabolism of type I and III collagens were studied in fibroblast cultures and dermis from 25 unrelated patients including 23 with typical Marfan syndrome and two infants with a very severe clinical form of this syndrome. Electrophoretic analysis of collagen -chains, as well as one- and two-dimensional electrophoresis of collagen cyanogen bromide peptides, failed to show any evidence of primary structure defects or overmodification of lysine residues in these collagens. The proportion of hydroxylated prolyl residues in isolated 1(I) chains was also normal. There was a minimal increase in the proportion of type III collagen produced by nine cultures. The findings in this study indicate that the underlying molecular defects in the patients studied are unlikely to involve the structure of the main fibrillar type I and III collagens.     

Effect of the tenure dentin bonding system on leakage of light-activated liners

This study investigated the effect of the Tenure dentin bonding system on the sealing properties of four light-activated liners. Dentinal slot preparations were made in extracted human molars and "restored" with Cavalite, TimeLine, VLC Dycal, and Zionomer liners. Samples were immersed in 0.05 percent crystal violet solution for 2 hours, then embedded in clear casting resin, sectioned, and examined with an optical microscope. Our results indicated that the Tenure dentin bonding system reduced dye penetration around each of the light-activated liners tested. The Tenure/VLC Dycal system provided a more effective seal than the other liners.     

Preclinical pharmacology of the antitumor agentO-6-methylguanine in CDF1 mice

O-6-methylguanine (O6-mG), a guanine analog recently shown to be a potent inhibitor of alkylguanine-DNA alkyltransferase, has been found to potentiate the antitumor activity of nitrosoureas, in particular, carmustine (BCNU), in resistant cell lines (HT-29 mer+) and is targeted for development as a modulating agent with chloroethyl nitrosoureas. A high-performance liquid chromatography (HPLC) assay of O6-mG in plasma has been developed using a C18 reverse-phase column. O6-mG and the internal standard deoxyguanosine (dGuo) were eluted with a linear gradient of from 15% to 35% methanol in 0.5M ammonium acetate (pH 6.5) at a flow rate of 1 ml/min. The assay was linear over a 4-log concentration range with a detection limit of 0.1 g/ml. The within-run and between-run coefficients of variation (CV) were found to be 8.1% and 9.3%, respectively. The pharmacokinetics (PK) of O6-mG were investigated in healthy CDF1 mice following separate i.v. and i.p. administrations. At 20 mg/kg i.v., plasma O6-mG gave a biexponential profile with a terminal half-life (t_1/2) of 24 min and a total clearance (CLT) of 23.7 ml min^–1 kg^–1. Higher doses (40–80 mg/kg) revealed a fluctuating third phase, probably due to enterohepatic cycling. Dose-dependent kinetics as measured by CLT and area under the plasma-concentration curve (AUC) values were also seen. Following i.p. dosing, O6-mG was completely absorbed and available to the circulation. No acute toxicity was observed in the animals, except for mild sedation, a possible side effect of the 10% ethanol used in the formulation. Studies on the cellular metabolism of highly purified [³H]-O6-mG have shown that the compound is not anabolized by a human lymphoblastoid cell line (CEM). Biochemistry studies have shown that the parent molecule is inactivating the alkylguanine-DNA alkyltransferase (AGT), thus exerting its pharmacological effect.Abbreviations O6-mG O-6-methylguanine - HPLC high-performance liquid chromatography - PK pharmacokinetics - CLT total clearance - AUC area under the plasma concentration curve - AGT alkylguanine-DNA alkyltransferase - dGuo deoxyguanosine This work was supported in part by contract NO1-CM-97620 from the National Cancer Institute (NIH) and by the Neil Bogart Memorial Laboratories by the T. J. Martell Foundation for Cancer, Leukemia, and AIDS Research     

Tumour profile ofN-[2-(dimethylamino)ethyl]acridine-4-carboxamide after intraperitoneal administration in the mouse

N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (AC) is an experimental antitumour agent that is being considered for phase I trials. After i.p. administration of 150 mg/kg [³H]-AC to tumour-bearing mice, AC was absorbed rapidly into the plasma and tissues such as the heart, liver, kidney and brain but more slowly into the s.c. tumour. The maximal AC concentration (86±36 mol/kg) in the tumour occurred at 35–60 min and was 3-fold the maximal plasma concentration, which occurred at 15 min. Although higher maximal concentrations were observed in other tissues, these concentrations fell rapidly in parallel with plasma concentrations. In contrast, AC concentrations in the tumour remained elevated, thet1/2 value (16.3 h) and mean residence time (MRT, 9.5 h) being prolonged in comparison with those in the plasma and other tissues (t1/2 range, 1.0–2.9 h; MRT, 1.2–1.4 h). AC concentrations were not detectable by our high-performance liquid chromatographic (HPLC) method (limit of detection, 0.02 mol/l) in the plasma or other tissues at 24 or 48 h after administration but were measurable in the tumour (1.6±0.8 and 0.6±0.3 mol/kg, respectively). Radioactivity concentrations in the plasma, tissues and tumour were very variable but were greater than the corresponding levels of unchanged parent AC. By 24 h, radioactivity concentrations in the plasma, tissues and tumour had fallen to similar levels with prolonged elimination profiles. Thus, the exposure of the s.c. implanted tumour to a threshold AC concentration for a prolonged time (>24 h) may partly explain the greater efficacy of AC against this tumour, whereas the shorter period of exposure of blood and other tissues may explain its low haematological toxicity.     

Two-pulse monocular and binocular interactions at the differential luminance threshold

Interaction between two pulses at the differential luminance threshold was studied for stimuli pairs presented to the same eye or to opposite eyes with an interocular delay. With monocular stimuli, the results replicated the earlier observations by Ikeda (1965) and Rashbass (1970) indicating linear interaction followed by rectification occurring at about 50-60 msec into the integration epoch. Binocular results were different, in accord with observations made in the contrast domain by Green and Blake (1981). Binocular stimuli of opposite polarity showed no cancellation. Binocular facilitation at threshold was found when either the stimuli of the same sign (+ + or - -) occurred with little interocular delay (stimulus onset asynchrony, SOA less than 15 msec), or the stimuli of the opposite sign (+ - or - +) were presented with an interocular delay between 15 and 100 msec SOA; the latter effect was at maximum with flashes 50 msec in duration presented with 50 msec interocular SOA. These results imply that binocular interaction takes place between rectified internal effects of luminance pulses. From the two-channel binocular model of Cogan (1987), binocular facilitation is attributed to the "fused" response derived from multiplicative excitation between same-sign (half-wave rectified), internal pulse responses. The absence of cancellation between simultaneous opposite-sign dichoptic stimuli is attributed to the "either-eye" binocular process dealing with full-wave rectified internal pulse responses to transient stimuli.     

Stages of adolescent tobacco-use acquisition

The present study extended the results of previous research in applying the "stages of acquisition" model to the onset of smokeless tobacco as well as cigarette use. Three expert judges classified an initial pool of items as to whether they represented "precontemplation," "contemplation," "action," or "maintenance" stages of smokeless tobacco acquisition. Fifty items with adequate inter-rater reliability were combined with 21 previously developed items pertaining to cigarette smoking acquisition in an overall tobacco acquisition questionnaire, which in turn was administered to 358 junior and senior high public school students. Three distinct components labeled precontemplation, action, and maintenance were delineated through principal component analyses. Coefficient alphas and discriminant analyses according to self-reported use demonstrated adequate reliability and validity for the new smokeless tobacco- and previously developed smoking-acquisition scale.