Immunohistochemical localization of gamma-aminobutyric acid (GABA) in the rat pancreas

The localization of gamma-aminobutyric acid (GABA) in rat pancreas was investigated using antiserum raised against GABA conjugated to bovine serum albumin with glutaraldehyde. Immunoreactive cells were only found in the center of the pancreatic islets, and these cells were surrounded by nonimmunoreactive cells. When two serial sections of rat pancreas were consecutively stained with GABA antiserum and with antibodies against insulin, both antisera stained the same population of endocrine cells within the islets. In rats pretreated with streptozotocin, a B-cell toxin, we observed a marked decrease in the number of cells exhibiting GABA-like immunoreactivity. These observations indicate that GABA is present in the B cells of rat pancreatic islets.     

Common misinterpretations of the “linear,no-threshold” relationship used in radiation protection

Summary Absorbed doseD is shown to be a composite variable, the product of the fraction of cells hit (I _H ) and the mean dose (hit size)z to those cells.D is suitable for use with high level exposure (HLE) to radiation and its resulting acute organ effects because, sinceI _H = 1.0, it approximates closely enough the mean energy density in the cell as well as in the organ. However, with low level exposure (LLE) to radiation and its consequent probability of cancer induction from a single cell, stochastic delivery of energy to cells results in a wide distribution of hit sizesz, and the expected mean value,z, is constant with exposure. Thus, with LLE, onlyI _H varies withD so that the apparent proportionality between dose and the fraction of cells transformed is misleading. This proportionality therefore does not mean that any (cell) dose, no matter how small, can be lethal. Rather, it means that, in the exposure of a population of individual organisms consisting of the constituent relevant cells, there is a small probability of particle-cell interactions which transfer energy. The probability of a cell transforming and initiating a cancer can only be greater than zero if the hit size (dose) to the cell is large enough. Otherwise stated, if the dose is defined at the proper level of biological organization, namely, the cell and not the organ, only a large dosez to that cell is effective.Dedicated to Prof. L.E. Feinendegen on the occasion of his 60th birthday     

Glycerol production in relation to the ATP pool and heat production rate of the yeasts Debaryomyces hansenii and Saccharomyces cerevisiae during salt stress

Changes in glycerol production and two parameters related to energy metabolism i. e. the heat production rate and the ATP pool, were assayed during growth of Saccharomyces cerevisiae and Debaryomyces hansenii in 4 mM and 1.35 M NaCl media. For both of the yeasts, the specific ATP pool changed during the growth cycle and reached maximum values around 10 nmol per mg dry weight in both types of media. The levels of glycerol were markedly enhanced by high salinity. In the presence of 1.35 M NaCl, D. hansenii retained most of its glycerol produced intracellularly, while S. cerevisiae extruded most of the glycerol to the environment. The intracellular glycerol level of S. cerevisiae equalled or exceeded that of D. hansenii, however, with values never lower than 3 mol per mg dry weight at all phases of growth. When D. hansenii was grown at this high salinity the intracellular level of glycerol was found to correlate with the specific heat production rate. No such correlation was found for S. cerevisiae. We concluded that during salt stress, D. hansenii possesses the capacity to regulate the metabolism of glycerol to optimize growth, while S. cerevisiae may not be able to regulate when exposed to different demands on the glycerol metabolism.     

Expression of a beta thalassemia gene with abnormal splicing.

Expression of a cloned human beta thalassemia gene with a single base change at position 5 of IVS 1 has been analyzed 48 hours after transfer of the gene into HeLa cells (transient expression). Little or no normal beta globin mRNA accumulates in the presence of the abnormal beta gene in contrast to significantly more normal beta mRNA produced with other mutations at this same position. By contrast, large amounts of an abnormal beta globin mRNA are present; this is due to the use of a cryptic 5' splice site in exon 1 rather than the normal 5' splice site of IVS 1. The results indicate the variability of the effect on RNA splicing of different single base defects within IVS.     

Silica and Ash in Native Plants of the Central and Southeastern Regions of the United States

Ash and silica contents and depositional patterns were determinedfor different tissues of 11 plants growing in the southeasternand central parts of the USA. Silica content was high in theleaves, sheaths and inflorescences of the grasses studied, especiallyso in the inflorescence of the C₃ grass, Stipa comata Trise.and Rupr. The ash content was especially high in leaves of Polymniauvedalia L., which are also high in calcium. Calcium depositionwas largely in trichomes and in veins of the leaf. Energy-dispersiveX-ray analysis showed that the distribution of the element siliconis closely related to certain epidermal structures such as ridges,cell walls, rows of irregularly-shaped structures lying lenghthwisealong the leaf, dumb-bell shaped structures and trichomes. Thesestructures also correspond to the phytoliths left behind afterdecay of the plant. The C₃ grasses differed from the C₄ in thatthey showed oval structures and produced correspondingly ovalphytoliths. Silicified trichomes (particularly in the C₃ grasses)and long, narrow, silica fibres were common in the inflorescencesof the grasses studied. These sharp particles could be irritatingto oesophageal and other tissues. Similar fibres in other grasseshave been implicated in certain cancers. High silicificationof the inflorescence structures might afford protection forthe seed, as reported for other grasses. C₃ and C₄ grasses, silica and ash content, scanning electron microscopy, energy-dispersive X-ray analysis, silicon distribution, spectra of elements in plants, trichomes, silica fibres, phytoliths     

Hydrolysis of N3-methyl-2'-deoxycytidine: model compound for reactivity of protonated cytosine residues in DNA

Protonation of cytosine residues at physiological pH may occur in DNA as a consequence of both alkylation and aberrant base-pair formation. When cytosine derivatives are protonated, they undergo hydrolysis reactions at elevated rates and can either deaminate to form the corresponding uracil derivatives or depyrimidinate generating abasic sites. The kinetic parameters for reaction of protonated cytosine are derived by studying the hydrolysis of N3-methyl-2'-deoxycytidine (m3dC), a cytosine analogue which is predominantly protonated at physiological pH. Both deamination and depyrimidimation reaction rates are shown to be linearly dependent upon the fraction of protonated molecules. We present here thermodynamic parameters which allow determination of hydrolysis rates of m3dC as functions of pH and temperature. Protonation of cytosine residues in DNA, as induced by aberrant base-pair formation or base modification, may accelerate the rate of both deamination and depyrimidation up to several thousand-fold under physiological conditions.     

Characterization of aminoalkylimidazol-4-one mutagens from liquid-reflux models

A new class of low molecular weight, aminomethylimidazol-4-one (IQ-"like") mutagens have been produced by the reaction of creatinine with the amino acid L-threonine, in liquid-reflux models, mimicking cooking, of diethylene glycol:5% distilled water (2 h at 150 degrees C). Two mutagens, 2-amino-1-methyl-5-propylideneimidazol-4-one (AMPI) and 2-amino-5-ethylidene-1-methylimidazol-4-one (AEMI) were isolated and characterized by UV absorption spectra, mass spectra, and 1H-NMR. The mutagen AEMI was identical to that obtained from the reaction of creatinine with acetaldehyde. These mutagens were positive in all IQ-sensitive Ames tester strains and were not inactivated by acidic nitrosation at pH 1.0. Products displaying mutagenicity were also obtained by refluxing creatinine with other hydroxyamino acids such as L-serine, L-homoserine, and L-4-amino-3-hydroxybutyric acid, and aldehydes such as glyoxal, methylglyoxal, glycolaldehyde, but not formaldehyde. Simple model systems such as creatinine and acetaldehyde may be useful in more clearly defining the exact mechanism of formation of IQ-type mutagens (aminomethylimidazo-quinolines and -quinoxalines) produced during cooking, as well as in screening for potential inhibitors of IQ-type mutagen formation, and elucidating the mechanism of such inhibition.