The emergence of 6-thioguanine-resistant lymphocytes in pediatric cancer patients

This paper describes a prospective study and a simultaneous longitudinal study of the frequency of 6-thioguanine- (6TG-) resistant peripheral blood lymphocytes in children with cancer and in controls. Thioguanine resistance was measured autoradiographically by the ability of phytohemagglutinin-stimulated lymphocytes to incorporate tirtiated thymidine in the presence of absenve of 2 × 10^?4 or 2 × 10^?5 M 6TGA. 5 of 29 untreated cancer patients had higher frequencies of 6TG-resistant lymphocytes than any of 116 controls. Patients receiving chemotherapy or radiation therapy showed significantly higheer numbers of 6TG-resistant lymphocytes than controls, and in rare patients abnormally high frequencies of 6TG-resistant cells persisted after therapy was discontinued. Among 22 patients prospectively before and during therapy, the frequency of 6TG-resistant lymphocytes was significantly higher during therapy. From these results we conclude (1) that some cancer patients have abnormally high frequencies of 6TG-resistant lymphocytes, and (2) cancer therapy either causes selection of 6TG-resistant cells or causes a phenotypic or genotypic change leading to further increases in frequencies of 6TG resistance.     

Mapping of the human lambda immunoglobulin variable gene subgroup 1

We describe the cloning and mapping of 20 putative members of the IGLV subgroup 1. These gene segments are contained on 26 phage clones which fall into 7 contigs plus one solitary phage. This represents approximately 240 kilobases (kb) of cloned DNA. Like IGLC gene segments, the IGLV gene segments were found to be oriented proximal to distal on the chromosome, indicating IGL somatic rearrangement is by deletion. The gene segments were placed on a long-range map of the IGL locus, which covers at least 800 kb. Clones were further ordered by pulsed field gel electrophoresis analysis of B-cell lines known to produce IGL-containing immunoglobulins. DNA deletions ranged from 120 to 570 kb.     

Unique human neutrophil populations are defined by monoclonal antibody ED12F8C10.

A mouse IgG1 monoclonal antibody ED12F8C10 (C10) binds a constant percentage of peripheral blood neutrophils in the same individual when studied over time, defining a distinct subset of neutrophils in all normal individuals studied to date. Bone marrow studies confirm that the heterogeneity is present to the same degree at all stages of neutrophil development from the myelocyte to the mature neutrophil. Neither in vivo nor in vitro activation of neutrophils explains or significantly alters the relative percentages of C10-positive and -negative neutrophils in the same individual. With both activation and exudation, however, expression of the C10-defined epitope increases in intensity in the C10 binding subpopulation. Studies of NBT reduction, phagocytosis, adherence, light scattering characteristics, and monoclonal antibody surface binding have failed to demonstrate physical or functional differences between the C10-defined populations. We examined C10 binding in patients with different defects of phagocyte function. In two patients with neutrophil-specific granule deficiency, less than 1% of the neutrophils were found to be C10 positive, while neutrophils from a patient with idiopathic leukemoid reaction and recurrent infections demonstrated greater than 99% C10 binding. Although the present study does not delineate the physiologic significance of C10 binding heterogeneity, it firmly supports the concept of neutrophil heterogeneity at the level of surface antigen expression.     

Oral chemical irritation: does it reduce perceived taste intensity?

In an experiment in which capsaicin was presented in physicalmixture with taste stimuli, no reduction in perceived tasteintensity, relative to the control condition, was observed.This result is inconsistent with previous reports of taste intensityreductions when oral chemical irritants were only periodicallyinterspersed among taste stimuli (Lawless et al., 1985; Lawlessand Stevens, 1984). A second experiment directly compared thetwo presentation formats and their respective control conditionsin a repeated-measures design. The results of that test confirmthat greater apparent reductions in taste intensity are observedwhen the oral irritant is presented as a periodic rinse eventhough perceived irritation under rinse conditions regularlyfalls to levels significantly below those maintained with mixturepresentations. This observation indicates that much of the apparentmasking of taste intensity in the presence of oral irritationis not directly related to irritation level but is sensitiveto procedural variation.     

Evaluating the 'Labeled Magnitude Scale' for Measuring Sensations of Taste and Smell

The Labeled Magnitude Scale (LMS) is a semantic scale of perceptualintensity characterized by a quasi-logarithmic spacing of itsverbal labels. The LMS had previously been shown to yield psychophysicalfunctions equivalent to magnitude estimation (ME) when gustatory,thermal and nociceptive stimuli were presented and rated together,and the upper bound of the LMS was defined as the ‘strongestimaginable oral sensation’. The present study comparedthe LMS to ME within the more limited contexts of taste andsmell. In Experiment 1, subjects used both methods to rate eithertaste intensity produced by sucrose and NaCl or odor intensityproduced by acetic acid and phenyl ethyl alcohol, with the upperbound of the LMS defined as either the ‘strongest imaginabletaste’ or the ‘strongest imaginable odor’.The LMS produced psychophysical functions equivalent to thoseproduced by ME. In Experiment 2 a new group of subjects usedboth methods to rate the intensity of three different tastequalities, with the upper bound of the LMS defined as the ‘strongestimaginable [sweetness, saltiness, or bitterness]’. Inall three cases the LMS produced steeper functions than didME. Experiment 3 tested the hypothesis that the LMS yields datacomparable to ME only when the perceptual domain under studyincludes painful sensations. This hypothesis was supported whenthe LMS again produced steeper functions than ME after subjectshad been explicitly instructed to omit painful sensations (e.g.the ‘burn’ of hot peppers) from the concept of ‘strongestimaginable taste’. We conclude that the LMS can be usedto scale sensations of taste and smell when they are broadlydefined, but that it should be modified for use in scaling specifictaste (and probably odor) qualities. The implications of theseresults for theoretical issues related to ME, category-ratioscales and the size of the perceptual range in different sensorymodalities are discussed. Chem. Senses 21: 323–334, 1996.     

A relational database for sequence-specific protein NMR data

Summary A protein NMR database has been designed and is being implemented. The database is intended to contain solution NMR results from proteins and peptides (larger than 12 residues). A relational database format has been chosen that indexes data by: primary journal citation, molecular species, sequence-related and atom-specific assignments, and experimental conditions. At present, all data are entered from the primary refereed literature. Examples are given of sample queries to the database. Possible distribution formats are discussed.     

Western pine beetle voltinism in a changing California climate

1. Recent hot droughts in California resulted in ponderosa pine (Pinus ponderosa) mortality attributed to drought and western pine beetle (WPB, Dendroctonus brevicomis). While drought alone can cause tree death, direct warming effects on WPB are a contributing factor. Research on WPB generation timing (voltinism), however, is lacking.
2. We monitored WPB tree attacks and adult emergence timing at two California sites and developed a degree-day model from field-observed data. Historical, contemporary, and future temperatures for several California sites were used with the model to examine trends in WPB voltinism.
3. Field data showed a single summer and an overwinter generation at a northern California site. As summer temperatures increased beyond 1900–1980 averages, the predicted number of full and partial WPB generations by 2021 had increased from ~2 annual (one summer and one overwinter) generations historically to ~2.3 at two northern California sites and from ~2.3 to ~3.2 at two warmer California sites.
4. Historical and contemporary data suggest winter warming was not sufficient for an additional generation overwinter. Instead, increases in generations were driven by summer and fall temperatures.
5. Unconstrained increases in the number of future annual generations will be limited by complex, but not well understood, WPB thermal adaptations. Increased knowledge of temperature-driven WPB population growth will improve forest vegetation models aimed at predicting ponderosa pine mortality in a changing climate.