Incidence of chromosome abnormalities in newborn children. Comparison between incidences in 1969–1974 and 1980–1982 in the same area

Summary As part of an ongoing study of the influence of environmental factors on pregnancy, childbirth, and fetuses, comparisons have been made between incidences in 1969–1974 and in 1980–1982 of chromosome aberrations in liverborn children in the same area of Denmark. The incidence of chromosome aberrations in the first period was 2.6 per 1000, compared with 4.1 per 1000 during the latter period. However, the difference was mainly due to an increase in inversions, and this in turn was due to a difference in chromosome staining methods between the two periods.It is concluded that the Danish study and similar studies in the United States, Canada, and Scotland indicate that early detection of chromosome aberrations by chromosome examination at birth is indicated in order to be able to inform and counsel parents of children with chromosome aberrations. Chromosome examination at birth is also of importance in the diagnosis of structural inheritable chromosome aberrations and consequent family investigation and genetic counseling.     

Formation of (4R)- and (4S)-4-hydroxyochratoxin A from ochratoxin A by liver microsomes from various species.

Two metabolic products were formed from ochratoxin A by human, pig, and rat liver microsomal fractions in the presence of reduced nicotinamide adenine dinucleotide phosphate. They were isolated from the incubation mixture in the presence of pig liver microsomes by extraction, thin-layer chromatography, and high-pressure liquid chromatography Their structures are suggested to be (4R)- and (4S)-4-hydroxyochratoxin A on the basis of mass and nuclear magnetic resonance spectroscopy. Km and the maximum velocity for the formation of the two metabolites by human, pig, and rat microsomes were determined. Their formation was inhibited by carbon monoxide and metyrapone. The results indicate that the microsomal hydroxylation system is a cytochrome P-450 and that different species are involved in the formation of the two epimeric forms of 4-hydroxyochratoxin A.     

Cloning and expression of the beta-D-phosphogalactoside galactohydrolase gene of Lactobacillus casei in Escherichia coli K-12.

Lactose metabolism in Lactobacillus casei 64H is associated with the presence of plasmid pLZ64. This plasmid determines both phosphoenolpyruvate-dependent phosphotransferase uptake of lactose and beta-D-phosphogalactoside galactohydrolase. A shotgun clone bank of chimeric plasmids containing restriction enzyme digest fragments of pLZ64 DNA was constructed in Escherichia coli K-12. One clone contained the gene coding for beta-D-phosphogalactoside galactohydrolase on a 7.9-kilobase PstI fragment cloned into the vector pBR322 in E. coli strain chi 1849. The beta-D-phosphogalactoside galactohydrolase enzyme isolated from E. coli showed no difference from that isolated from L. casei, and specific activity of beta-D-phosphogalactoside galactohydrolase was stimulated 1.8-fold in E. coli by growth in media containing beta-galactosides. A restriction map of the recombinant plasmid was compiled, and with that information, a series of subclones was constructed. From an analysis of the proteins produced by minicells prepared from transformant E. coli cells containing each of the recombinant subclone plasmids, it was found that the gene for the 56-kilodalton beta-D-phosphogalactoside galactohydrolase was transcribed from an L. casei-derived promoter. The gene for a second protein product (43 kilodaltons) was transcribed in the opposite direction, presumably under the control of a promoter in pBR322. The relationship of this second product to the lactose metabolism genes of L. casei is at present unknown.     

Rescue of mitomycin C- or psoralen-inactivated Micrococcus radiodurans by additional exposure to radiation or alkylating agents

The processing of damaged DNA was altered in a mitomycin C-sensitive mutant (mtcA) of Micrococcus radiodurans. Even though the mutant retained resistance to 254-nm UV radiation, it did not, in contrast to the wild-type strain, show any excessive DNA degradation or cell death when incubated with chloramphenicol after sublethal doses of either UV light or mitomycin C. The results suggest the constitutive synthesis of an enzyme system responsible for wild-type proficiency in the repair of mitomycin C-induced damage. An alternative system able to repair damage caused by mitomycin C was demonstrated in the mtcA background. In this strain, additional damage inflicted upon the cellular DNA effected a massive rescue of cells previously inactivated by mitomycin C. Rescue was provoked by ionizing radiation, by UV light, or by simple alkylating agents. Cells treated with psoralen plus near-UV radiation could be rescued only when inactivation was due primarily to psoralen-DNA interstrand cross-links rather than to monoadducts. The rescue of inactivated cells was prevented in the presence of chloramphenicol. These results can be interpreted most readily in terms of an alternative repair system able to overcome DNA interstrand cross-links produced by mitomycin C or psoralen plus near-UV light, but induced only by the more abundant number of damages produced by radiation or simple alkylating agents.     

Current-voltage curve of electrogenic Cl− pump predicts voltage-dependent Cl− efflux inAcetabularia

Summary The current-voltage relationship of carrier-mediated, passive and active ion transport systems with one charge-carrying pathway can exactly be described by a simple reaction kinetic model. This model consists of two carrier states (one inside, one outside) and two pairs (forwards and backwards) of rate constants: a voltage-dependent one, describing the transport of charge and a voltage-insensitive one, summarizing all the other (voltage-independent) reactions. For the electrogenic Cl^– pump inAcetabularia these four rate constants have been determined from electrical measurements of the current-voltage relationship of the pump (Gradmann, Hansen & Slayman, 1981;in: Electrogenic Ion Pumps, Academic Press, New York). The unidirectional Cl^– efflux through the pump can also be calculated by the availiable reaction kinetic parameters.³⁶Cl^– efflux experiments on singleAcetabularia cells with simultaneous electrical stimulation (action potentials) and recording, demonstrate the unidirectional Cl^– efflux to depend on the membrane potential. After subtraction of an efflux portion which bypasses the pump, agreement is found between the measured flux-voltage relationship and the theoretical one as obtained from the reaction kinetic model and its parameters from the electrical data.     

Rats chronically injected with urine from Huntington's chorea patients do not striatal damage

Rats were injected subcutaneously for 147 consecutive days with large volumes of urine from control subjects and from patients with Huntington's chorea (HC) in an effort to test for presence of a possible neurotoxic substance in HC. No evidence of illness was observed in animals treated with HC urine, and their behavior did not differ from animals treated with control urine. After rats were sacrificed, striatum was examined for the biochemical and neuropathological changes seen in human striatum in HC. No deficiency of γ-aminobutyric acid content, nor reduction in activities of glutamic acid decarboxylase and choline acetyltransferase, was found in striatum of rats chronically treated with HC urine. Also, no significant differences were found between striatum of control and experimental rats by light or electron microscopy. These results neither support for exclude the possibility of a neurotoxic mechanism for the neuronal loss characteristic of HC.     

Early ultrastructural changes in the myocardium following thyroxine-induced hypertrophy

The model of myocardial hypertrophy induced by thyroxine was studied with particular regard to the early ultrastructural changes in fractional volume of the mitochondria and myofibrils, and capillary distribution. Following injections of L-thyroxine (25 mg/kg IP) for 9 consecutive days, rats were sacrificed by vascular perfusion and cardiac tissue samples from the mid-wall zone of the left ventricle were processed routinely for electron microscopy. Heart weight/body weight ratios of thyroxine treated (T) rats showed a significant increase (P less than 0.001) over the ratios in control (C) rats. Likewise, the fractional volume of mitochondria (42%) was significantly increased (P less than 0.001) in the myocardium of T rats when compared with C rats (31%). However, the fractional volume of myofibrils was significantly decreased in the myocardium of T rats (P less than 0.001) and there was no significant difference between the hearts of T and C rats with respect to capillary luminal area/myocyte area. The mitochondria/myofibril ratio was increased in the hearts of T rats (0.82) over that found in control hearts (0.52). These results suggest that in the early stages of thyroxine-induced myocardial hypertrophy there is not an immediate increase in capillary area which may account for the ischemia and significant increase in mitochondrial volume which characterized myocardial hypertrophy in this model.     

The effect of photoperiod on serum concentrations of luteinizing and follicle stimulating hormones in prepubertal heifers following ovariectomy and estradiol injection

Eleven heifers, between 63 and 197 days of age, were exposed to 18 hr light/day (L) or natural photoperiods (N), beginning October 19, 1979. They were ovariectomized 8 weeks later. LH concentrations after ovariectomy were not affected by photoperiod, but the rate of increase of FSH after ovariectomy was greater (P<0.10) for group L than for group N. Three weeks after ovariectomy, heiters were injected, IV, with 0.1 mug/kg estradiol-17beta. LH concentrations initially decreased after injection. This was followed by a series of pulses larger than those prior to injection. FSH concentrations declined after injection and remained low throughout the sampling period. The net response of LH concentrations to estradiol (mean post-injection concentration minus mean pre-injection concentration) was greater (P=0.05) for group L (4.7 +/- 0.49 ng/ml) than for group N (2.9 +/- 0.37 ng/ml). Photoperiod did not affect the net response of FSH concentrations to estradiol. We concluded that exposing prepubertal heifers to 18 hr light/day during the winter resulted in a greater rate of increase of FSH after ovariectomy and greater estrogen-induced LH release. Because the response of LH to estradiol-17beta differed from the response of FSH, these hormones may be regulated differently.