The 2,4-dinitrophenyl group for protection of hydroxyl function of tyrosine during solid-phase peptide synthesis

The facile thiolytic cleavage of the O-2,4-dinitrophenyl (Dnp) tyrosine bond was applied to the solid-phase synthesis of the 22-amino acid residue peptide H-Asp-Ala-Val-Tyr -Thr-Gly-Leu-Asn-Thr-Arg-Asn-Gln-Glu-Thr-Tyr -Glu-Thr-Leu-Lys-His-Glu-Lys-OH, corresponding to positions 62-83 in the chain of the type 1 receptor for Fc_ε, domains expressed on the rat mucosal-type mast cells (line RBL-2H3). A method for the spectrophotometric determination of insoluble O-Dnp as well as of unprotected phenolic moieties of tyrosine was developed. It is based on monitoring S-Dnp-2-mercaptoethanol, produced upon O-Dnp thiolysis by 2-mercaptoethanol. © Munksgaard 1995. Dedicated to the memory of Dr. Susumu Funakoshi, a dear friend and a leader in peptide chemistry.     

Influence of Viral Infections on Body Weight, Survival, and Tumor Prevalence of B6C3F1 (C57BL/6N ? C3H/HeN) Mice in Carcinogenicity Studies

Sendai virus (SV), mouse hepatitis virus (MHV), and pneumoniavirus of mice (PVM) are common viral infections of mice. Influenceof these viral infections on the prevalence of liver tumors,lung tumors, and lymphoma is of concern in chemical carcinogenicitystudies. Body weight, survival, and tumor prevalence of B6C3F1mice with and without viral infections in 33 male and 34 femaleuntreated control groups and 32 male and 32 female low- andhigh-dose groups of 2-year chemical carcinogenicity studieswere evaluated. In male mice, the SV infection was associatedwith significantly (p < 0.05) higher survival of control,low-dose, and high-dose groups, and higher prevalence of livertumors and lymphoma. The increases in tumor prevalence are possiblydue to an increase in the survival of male mice that had SVinfection. However, when interlaboratory variability and time-relatedeffects were taken into account, the number of significant effectswas consistent with the expected false-positive rate inherentto the statistical procedures. The MHV and PVM infections didnot cause consistent changes in body weight, survival, and tumorprevalences in the control and chemical treatment groups ofmale mice. Viral infections did not cause consistent increasesor decreases in body weight, survival, or tumor prevalence inthe control and chemical treatment groups of female B6C3F1 mice.     

Preclinical Toxicology Studies with Acyclovir: Genetic Toxicity Tests

Preclinical Toxicology Studies with Acyclovir: Genetic ToxicityTests. Clive, D., Turner, N.T., Hozier, J., Batson, A.G. andTucker, W.E., Jr. (1983). Fundam. Appl. Toxicol 3: 587–602.Acyclovir (ACV), an antiviral drug active in the treatment oforal and genital Herpes infections, has been evaluated for mutagenicand carcinogenic potential in a battery of in vitro and in vivoshort-termassays. Negative results were obtained in the following in vitrotests: Ames Salmonella, plate incorporation and preincubationmodification assays; E. coli polA⁺/polA^– DNA repair; yeast(S. cerevisiae D4) gene conversion; Chinese hamster ovary cells(HGPRT, APRT loci and ouabain-resistance marker); L5178 Y mouselymphoma cells (HGPRT locus and ouabain-resistance marker);and C3H/10Tmouse fibroblast neo-plastic transformation assay.All except the last assay were performed in the presence andabsence of an exogenous metabolic activation system. ACV waspositive at high concentrations x exposure times in the absenceof exogenous metabolic activation in the following in vitrosystems and at the indicated concentrations: BALB/c-3T3 neoplastictransformation (50 /µg/mL, 72 h exposure); human lymphocytecytogenetics (250–500 µg/mL, 48 h exposure); andL5178Y mouse lymphoma cells (TK locus, 400–2400 µg/mL,4 h exposure; predominantly small colony mutants of chromosomalorigin produced). No effects were seen in vivo (mouse dominantlethal assay; rat and Chinese hamster bone marrow cytogenetics)at up to maximum tolerated doses (MTD). An unusual clastogeniceffect was seen in Chinese hamsters at 5 times the MTD. Overall,positive effects were seen only at either high concentrations(250 µg/mL in vitro or plasma levels) or prolonged exposure(72 hr in the BALB/ c-3T3 neoplastic transformation assay).These studies support the view that ACV is a chromosomal mutagen,i.e., one which causes multi-locus damage but not single geneeffects. The significance of these results for the genetic riskof ACV to man is discussed.     

Acrylamide: Dermal Exposure Produces Genetic Damage in Male Mouse Germ Cells

Acrylamide is used extensively in sewage and wastewater treatmentplants, in the paper and pulp industry, in treatment of potablewater, and in research laboratories for chromatography, electrophoresis,and electron microscopy. Dermal contact is a major route ofhuman exposure. It has been shown that acrylamide is highlyeffective in breaking chromosomes of germ cells of male miceand rats when administered intraperitoneally or orally, resultingboth in the early death of conceptuses and in the transmissionof reciprocal translocations to live-born progeny. It is nowreported that acrylamide is absorbed through the skin of malemice, reaches the germ cells, and induces chromosomal damage.The magnitude of genetic damage appears to be proportional tothe dose administered topically.     

A Tridimensional View of Intradermal Nevi as Revealed by Scanning Electron Microscopy

When scanning electron microscopy (SEM) was applied to the study of intradermal nevi, interesting tridimensional features were recognized. The free surface of the lesions showed ruffled keratinized cells. "Normal" hairs as well as "corkscrew" hairs emerged from the follicular openings. Nevus cells were either round or elongated and surrounded by connective tissue fibers.     

Mode of Onset of Malignant Ventricular Arrhythmias in Idiopathic Ventricular Fibrillation

Mode of Onset of Idiopathic VF. Introduction : The mode of onset of malignant ventricular arrhythmias (ventricular tachycardia [VT] or ventricular fibrillation [VF] has been well described in patients with organic heart disease and in patients with the long QT syndromes. Less is known about the mode of onset of VF in patients with out-of-hospital VF who have no evidence of organic heart disease or identifiable etiology.
Methods and Results : We reviewed the ECGs of all our patients with Idiopathic VF. Documentation of the onset of spontaneous arrhythmias was available for 22 VK episodes in 9 patients (6 men and 3 women; age 41 ± 16 years). In all instances, spontaneous VF followed a rapid polymorphic VT, which was initiated by premature ventricular complexes (PVCs) with very short coupling intervals. The PVC initiating VF had a coupling interval of 302 ± 52 msec and a prematurity index of 0.4 ± 0.07. These PVCs occurred within 40 msec of the peak of the preceding T wave. Pause-dependent arrhythmias were never observed.
Concltision : Cardiac arrest among patients with idiopathic VF has a very distinctive mode of onset. Documentation of a polymorphic VT that is not pause dependent is of diagnostic value.