Leukaemia and transient leukaemia in Down syndrome

Summary We have reviewed 215 published cases of leukaemia and transient leukaemia in Down syndrome. There is an over-representation of mosaic trisomy 21, possibly the result, at least in part, of a survival effect. The most intriguing observation is a bimodal distribution of maternal age, produced largely because cases with true leukaemia have a significantly higher maternal age than cases with transient leukaemia (33.5 versus 29.5 years). In conjunction with evidence that meiosis I non-disjunction is infrequent in transient leukaemia, this suggests different mechanisms for the etiology of leukaemia and transient leukaemia, and favours a locus predisposing to transient leukaemia proximal to the centromere on the long arm of chromosome 21.     

Sex determination in the dioecious Melandrium

Summary Melandrium album (2n=24), a dioecious species with heteromorphic sex chromosomes (XY, males and XX, females), has a strong genetic commitment for sex determination. We report here a procedure for obtaining haploid plants from cultured anthers and show that genotype, pollen stage, cold treatment and certain culture media components are essential for a reproducible yield of embryos. Our procedure increased the number of responsive anthers and not the number of responsive microspores per anther. Most likely, our experimental system allows the recovery of competent microspores, and this on a medium containing either an auxin or a cytokinin. All of the 36 anther-derived plants tested expressed a female phenotypic sex instead of the theoretical one male one female ratio. When analysed cytologically, the plants exhibited the corresponding female genetic sex (one or two X chromosomes).     

Spectral mechanisms in the tree squirrel retina

Summary The retina of the gray squirrel (Sciurus carolinensis) contains rods and cones in a ratio of about 23. The spectral mechanisms in this retina were examined in behavioral and electrophysiological experiments. Tests of color vision revealed that this animal has a spectral neutral point at about 500 nm and, thus, dichromatic color vision. Recordings made from single optic nerve fibers and results obtained from an analysis of the flicker photometric electroretinogram (ERG) indicated that vision in the gray squirrel is based on three spectral mechanisms. One of these, presumably rod-based, has peak sensitivity at about 502 nm. The other two mechanisms reflect the presence of two classes of cone having average peak sensitivity of about 444 nm and 543 nm.     

The effect of prolonged hypobaric hypoxia on growth of fetal sheep

The effect of prolonged hypobaric hypoxia on fetal sheep was studied. Pregnant ewes were subjected to an atmospheric pressure of 429 torr from 30 days to 135 days gestation (long-term study). Average fetal weight for the hypoxaemic group (3.35 +/- 0.53 kg; n = 4; mean +/- SD) was significantly lower than for the controls (4.23 +/- 0.29 kg; n = 7; P less than 0.05). A short-term study was undertaken with fetuses (n = 8) which were catheterized at 110 days gestation and whose dams were subjected to hypobaric hypoxia from 120 to 141 days gestation. The mean carotid PO2 of fetuses in the hypoxic group was 12.7 +/- 0.7 torr compared to 22.7 +/- 0.7 torr for the control group (n = 9; P less than 0.001) throughout the period of treatment. Fetal arterial oxygen content fell from 6.5 +/- 1.7 to 4.9 +/- 0.4 ml/dl (P less than 0.05), but rose to control values after 7 days due to an increase in fetal haemoglobin concentration (9.6 +/- 1.1 to 13.0 +/- 1.9 g/dl, P less than 0.001) and packed cell volume (33 +/- 3 to 45 +/- 4%, P less than 0.001). In the hypoxaemic fetuses, pH fell initially from 7.34 +/- 0.02 to 7.28 +/- 0.03 (P less than 0.05) and then recovered to 7.32 +/- 0.03 within 24 h. Mean fetal weight of the short-term hypoxic group was 3.46 +/- 0.72 kg compared to 4.15 +/- 0.51 for the control group (P less than 0.05). Both long- and short-term hypoxia produced a similar reduction in fetal body weight. The adrenal glands were significantly heavier in the hypoxic fetuses than in controls. Placental weight was not effected by hypoxia, but exposure from 30 days gestation reduced the average size of cotyledons (P less than 0.05). It is concluded that the fetal sheep increases its ability to acquire and transport oxygen in response to chronic hypoxia, but this compensation is not sufficient to prevent growth retardation or changes to the pattern of tissue growth.     

Topical chemotherapy of cutaneous Leishmaniasis

Cutaneous leishmaniasis (CL) is one of the most important causes of chronic ulcerative skin lesions. The disease is endemic in many parts of the world, presenting a range of clinical forms - acute, chronic, recurrent and diffuse(1). Several species of Leishmania are involved, including L. major, L. tropica and L. aethiopica in the Old World, and several members of the L. braziliensis and L. mexicana complexes in the New World. Some forms of the disease produce only mild, self-limited lesions, while at the other extreme are the destructive mucocutaneous forms caused by L. braziliensis and L. panamensis(1-7). In all cases, chemotherapy tends to be difficult - often requiring prolonged parenteral administration of toxic drugs such as pentavalent antimonials or amphotericin B. Such drugs are also expensive and relatively inefficient in the sense that much of the active ingredient is excreted by the patient before reaching its target. Consequently, there is renewed interest in the development of active formulations suitable for topical application directly onto the lesions.     

Cadmium-2-acetylaminofluorene interaction in isolated rat hepatocytes

Cadmium (Cd) is a non-essential, highly toxic heavy metal and a ubiquitous environmental contaminant. Evidence exists that Cd can affect parameters which are of great importance in the response towards xenobiotics. However, there is a lack of information about the mechanisms that take place at the cellular and molecular levels upon dual exposure to Cd and other toxins. The purpose of the present work was therefore to examine the biochemical interactions between Cd and a well-known genotoxic hepatocarcinogen, 2-acetylaminofluorene (AAF) in isolated rat hepatocytes. The cells were incubated for 10 hr with a sub-cytotoxic concentration (0.22 M) of ¹⁰⁹Cd. This was followed by a 10 hr exposure to 1 M [³H]AAF. Cellular distribution of Cd and ³H was determined. Sephadex G-75 elution profiles of the cytosol showed that Cd was almost entirely associated with the intermediate molecular weight (IMW) fractions containing metallothionein (MT) (>80%), and with high molecular weight proteins. In parallel, the highest proportion of ³H was found in the low molecular weight components. Further analysis of IMW fractions by DEAE A-25 anion-exchange chromatography revealed that, in addition to Cd, there was some ³H which coeluted along with MT-I and MT-II isoforms, but preferentially with MT-I. Moreover, Cd pretreatment caused a 1.6-fold increase in MT level, as measured by the silver-saturation assay. Under these conditions, there was a 17% lower binding of ³H to the DNA. This reduced binding was neither accompanied by diminished AAF uptake nor by inhibition of cytochrome P-450 activity. Taken together, these results suggest that Cd exposure has a protective effect against the genotoxicity of AAF. MT, whose synthesis is induced, could play a role in the Cd-AAF interaction through scavenging of reactive metabolites.Abbreviations AAF 2-acetylaminofluorene - Cd cadmium - DMSO dimethyl sulfoxide - HBSS Hank's balanced salt solution - LDH lactate dehydrogenase - MT metallothionein - UDS unscheduled DNA synthesis     

High threonine producer mutant ofNicotiana sylvestris (Spegg. and Comes)

Summary Mutagenesis and the subsequent selection of mesophyll diploid protoplasts ofNicotiana sylvestris on growth inhibitory concentrations of lysine plus threonine has led to the isolation of an LT-resistant mutant. Regeneration of this line (RLT 70) and analysis of its descendants demonstrated the dominant monogenic nuclear character of the resistance gene, further namedak-LT1. When the inhibition properties of aspartate kinase were examined in the homozygous mutant, lysine-sensitive activity could no longer be detected. In comparison, 70%–80% of the wild-type enzyme activity was usually inhibited by lysine, and the rest by threonine. Evidence for the existence of at least two AK isoenzymes was obtained by ion-exchange chromatography, where two peaks of activity could be detected: the first one to be eluted is lysine sensitive, and the second one threonine sensitive. One consequence of the altered regulation of AK in the mutant was the enhanced production of soluble threonine. Threonine accumulation was observed to occur throughout the life cycle of the mutant plant as well as in its different organs. In particular, leaves exhibited a 45-fold increment of soluble threonine, which corresponds to a 13-fold increase in total threonine: almost one-third of the total amino acids was free and proteinbound threonine. In RLT 70 seeds, 20% of the free amino acid pool was in the form of threonine (70-fold accumulation compared to the wild type), and total threonine content was increased five fold. As a general rule, the other amino acids were also more abundant in RLT 70 seeds, such that the total of amino acids present was between two to four times higher, but in contrast with the situation encountered in leaves, this was also due to a higher protein-bound amino acid content.     

Highly asymmetric intergeneric nuclear hybrids between Nicotiana and Petunia: evidence for recombinogenic and translocation events in somatic hybrid plants after “gamma”-fusion

Summary Extremely asymmetric nuclear hybrids have been obtained via protoplast fusion in an intergeneric combination. Irradiated (cobalt⁶⁰,100 krad) kanamycinresistant Petunia hybrida mesophyll protoplasts were chemically fused with wild-type mesophyll protoplasts of Nicotiana plumbaginifolia. Eighty-six hybrid colonies were selected on kanamycin-containing medium, and twenty-four of these could be induced to regenerate numerous shoots. Cytological analysis of the regenerants showed the presence of a few chromosome fragments in some lines, and even a metacentric chromosome in yet another line. Besides additional chromosome fragments some lines only possessed typical Nicotiana chromosomes, and this at the diploid (2n = 2X = 20) as well as the tetraploid (2n = 2X = 40) level. Biochemical analysis showed that all regenerants had neomycin phosphotransferase activity (NPTII), which suggests that intergenomic recombination and or translocation events took place at least in those lines where no additional chromosome fragments could be detected. The presence of the NPTII gene was shown by Southern hybridization. All regenerants tested were fertile, and the segregation ratios for the kanamycin gene (for self and backcross pollinations to the recipient partner) for some of the regenerants correspond with Mendelian rules for a monogenic dominant marker. Most of the regenerants showed abnormal segregation ratios; in this case, no correlation could be made between segregation ratio and chromosome composition.Our results demonstrate the existence of intergenomic recombination and translocations evens in nuclear somatic hybrid plants obtained via gamma-fusion.