DNA repair mutant pso2 of Saccharomyces cerevisiae is sensitive to intracellular acetaldehyde accumulated by disulfiram-mediated inhibition of acetaldehyde dehydrogenase.

Blocking aldehyde dehydrogenase with the drug disulfiram leads to an accumulation of intracellular acetaldehyde, which negatively affects the viability of the yeast Saccharomyces cerevisiae. Mutants of the yeast gene PSO2, which encodes a protein specific for repair of DNA interstrand cross-links, showed higher sensitivity to disulfiram compared to the wild type. This leads us to suggest that accumulated acetaldehyde induces DNA lesions, including highly deleterious interstrand cross-links. Acetaldehyde induced the expression of a PSO2-lacZ reporter construct that is specifically inducible by bi- or poly-functional mutagens, e.g., nitrogen mustard and photo-activated psoralens. Chronic exposure of yeast cells to disulfiram and acute exposure to acetaldehyde induced forward mutagenesis in the yeast CAN1 gene. Disulfiram-induced mutability of a pso2Delta mutant was significantly increased over that of the isogenic wild type; however, this was not found for acetaldehyde-induced mutagenesis. Spontaneous mutability at the CAN1 locus was elevated in pso2Delta, suggesting that growth of glucose-repressed yeast produces DNA lesions that, in the absence of Pso2p-mediated crosslink repair, are partially removed by an error-prone DNA repair mechanism. The use of disulfiram in the control of human alcohol abuse increases cellular acetaldehyde pools, which, based on our observations, enhances the risk of mutagenesis and of other genetic damage.

The influence of diffuse pollution on groundwater content patterns for the groundwater bodies of Germany.

Commissioned by Germany's Working Group of the Federal States on Water Problems (LAWA) the authors developed a procedure to define natural groundwater conditions from groundwater monitoring data. The distribution pattern of a specific groundwater parameter observed by a number of groundwater monitoring stations within a petrographically comparable groundwater typology is reproduced by two statistical distribution functions, representing the "natural" and "influenced" component. The range of natural groundwater concentrations is characterized by confidence intervals of the distribution function of the natural component. The applicability of the approach was established for 17 hydrochemical different groundwater typologies occurring throughout Germany. Based on groundwater monitoring data from ca. 26,000 groundwater-monitoring stations, 40 different hydrochemical parameters were evaluated for each groundwater typology. For all investigated parameters the range of natural groundwater concentrations has been identified. According to the requirements of the EC Water Framework Directive (article 17) (WFD) this study is a basis for the German position to propose criteria for assessing a reference state for a "good groundwater chemical status".

A procedure to define natural groundwater conditions of groundwater bodies in Germany.

Commissioned by Germany's Working Group of the Federal States on Water Problems (LAWA) the authors developed a procedure to define natural groundwater conditions from groundwater monitoring data. The distribution pattern of a specific groundwater parameter observed by a number of groundwater monitoring stations within a petrographically comparable groundwater typology is reproduced by two statistical distribution functions, representing the "natural" and "influenced" components. The range of natural groundwater concentrations is characterized by confidence intervals of the distribution function of the natural component. The applicability of the approach was established for four hydrochemically different groundwater typologies occurring throughout Germany. Based on groundwater monitoring data from 7920 groundwater monitoring stations, 15 different hydrochemical parameters were evaluated for each groundwater typology. For all investigated parameters the range of natural groundwater concentrations has been identified. According to the requirements of the EC Water Framework Directive (article 17) (WFD) this study is a basis for the German position to propose criteria for assessing a reference state for a "good groundwater chemical status".

Hypopituitarism and idiopathic delayed puberty: a longitudinal study in an attempt to diagnose gonadotropin deficiency before puberty.

Fifty-five hypopituitary patients (43 boys and 12 girls) treated with human GH were studied longitudinally before and during puberty, occurring either spontaneously or induced with testosterone enanthate (100 mg/month, im) in boys and ethinylestradiol (10 micrograms/day, orally) in girls. In addition, 53 boys with idiopathic delayed puberty (IDP) were studied. Gonadotropin integrated responses (IRs) during 90 min after the iv injection of 25 micrograms/m2 LRH, bone ages (BA), and plasma levels of dehydroepiandrosterone sulfate and testosterone were determined at least yearly. Prepubertal hypopituitary patients with gonadotropin deficiency were characterized by: 1) a lowered FSH IR to LRH in most boys and in all girls; 2) a low LH IR for BA; 3) adrenarche either absent or delayed BA; 4) height age close to BA; and 5) the presence of several pituitary deficiencies. In contrast, most prepubertal hypopituitary patients without gonadotropin deficiency showed: 1) a normal FSH IR to LRH; 2) a normal or intermediate (greater than or equal to 75 mIU/ml . 90 min) LH IR for BA; 3) a normal adrenarche for BA; 4) a height age below BA; and 5) isolated GH or GH plus TSH deficiencies. A significant linear correlation was found between LH IR and the logarithm of plasma testosterone. The slopes and levels were similar in controls and hypopituitary boy without gonadotropin deficiency. In IDP, the level was significantly higher. All data obtained in these patients show that the increase in plasma testosterone and the clinical onset of puberty are delayed for the observed pubertal pattern of LH responsiveness. It is concluded that the study of several clinical and biological features, especially the gonadotropin IR to LRH, are of predictive value for the diagnosis of normal or deficient gonadotropic function in prepubertal patients with IDP and hypopituitarism.

Pubertal growth and final height in hypopituitary boys: a minor role of bone age at onset of puberty.

Twenty-two hypopituitary boys treated with human GH were studied longitudinally before and during puberty. Eight patients entered spontaneous puberty at a mean bone age of 12.4 +/- 1.0 (+/- SD) yr. Height velocity reached a mean peak of 6.8 cm/yr during the second year of spontaneous puberty. In these patients, the mean total height gain throughout puberty was 22.8 +/- 5.2 cm, and the mean final height was 158.6 +/- 7.2 cm. Fourteen patients received testosterone enanthate (100 mg/month, im) starting at a mean bone age of 13.6 +/- 1.1 yr. Height velocity was maximal (7.5 cm/yr) during the first year of therapy. The mean final height was 162.9 +/- 5.0 cm, with a mean pubertal gain of 15.9 +/- 3.8 cm. Genital development, peak height velocity, and increase in plasma testosterone levels occurred earlier during testosterone therapy than during spontaneous puberty. In both groups of patients, there was a positive correlation between the bone age at onset of puberty and the height at onset of puberty (r = 0.65). There was also a negative correlation between bone age and total pubertal height gain (r = -0.73). This reduction in pubertal height increase was less than expected for bone age at onset of puberty, which can be explained by a decrease in bone age velocity in relation to bone age at onset of puberty (r = -0.81). Therefore, advancement in bone age at the onset of testosterone therapy did not impair final height, whereas it may increase height at onset of puberty, which is the major factor in final height. We conclude that in GH- and gonadotropin-deficient boys 1) a reduced dosage of testosterone enanthate (25 mg twice a month, im) should be used to induce pubertal development, and 2) the major criterion to decide when to give testosterone is height reached at that time regardless of bone age.

Trichothiodystrophy, mental retardation, short stature, ataxia, and gonadal dysfunction in three Moroccan siblings.

Three sibs, a boy and two girls, born to Moroccan consanguineous parents, were affected with a syndrome characterized by brittle hair, mental retardation, short stature, ataxia, and gonadal dysfunction. The hair in these three patients displayed the morphological and biochemical hallmarks of trichothiodystrophy (TTD). Gonadal function tests showed abnormal gonadotropic responses to LHRH, consistent with delayed puberty in the male and ovarian failure in both females. Comparison with previously reported cases of TTD associated with mental retardation suggests genetic heterogeneity, although specific biochemical markers are needed in order to answer this question.

Mapping of cytoskeletal components in the hippocampal formation of the tree shrew (Tupaia belangeri).

The distribution of the major cytoskeletal components in frontal cryosections of the hippocampal formation of adult male tree shrews (Tupaia belangeri) was immunohistochemically investigated by using commercially available antibodies. Actin-immunolabeling was evident in all layers of the dentate gyrus as well as in the regio superior (CA1) and the regio inferior (CA3). Neurofilament 160 was detected only in the molecular layer of the dentate gyrus and in the axons of the granule cells (mossy fibers). For beta-tubulin, the microtubule associated proteins (MAPs) MAP2AB, MAP2ABC and Tau, immunoreactivity was evident within the granule cells and within the somatodendritic compartment of pyramidal neurons. Granule cells and the somata of the pyramidal neurons were intensely labeled for kinesin. Our findings show the elaborate expression of cytoskeletal proteins in the hippocampal formation of the tree shrew, relatively similar to what is seen in other species but with also some important differences, such as the immunonegativity of the axonal compartment for Tau in the tree shrew, which is contrary to what we see in the mouse (unpublished data). These findings provide useful insights regarding the organization of the hippocampal formation of the tree shrew and are fundamental for further research in this field.

A direct radio-immunoassay for plasma delta 4-androstenedione. Application to children.

A RIA for the estimation of delta 4-androstenedione in human plasma without chromatographic purification is analyzed. Sensitivity, accuracy, precision and specificity are shown to be, at least, equivalent to those of methods involving chromatography.

N-demethylvancomycin, a novel antibiotic produced by a strain of Nocardia orientalis. Taxonomy and fermentation.

A novel vancomycin analog, N-demethylvancomycin, is produced by a soil isolate collected in Yucatan, Mexico. Taxonomic studies indicated this microorganism, designated NRRL 15232, is a strain of Nocardia orientalis. Unlike some glycopeptide antibiotics, virtually none of the N-demethylvancomycin synthesized remained bound to the cells of the producing culture. Antibiotic production was markedly depressed by the addition of orthophosphate to the fermentation medium. Enrichment of the medium with tyrosine, p-hydroxyphenylglycine, p-hydroxyphenylglyoxylic acid, or leucine, all putative precursors of the aglycone, stimulated the biosynthesis of N-demethylvancomycin.

New azasteroidal antifungal antibotics from Geotrichum flavo-brunneum. I. Discovery and fermentation studies.

Although Geotrichum species occur ubiquitously, antibiotic production by members of this genus has not previously been reported. The antibiotic complex designated A25822, consisting of one major and six minor structurally-related components active primarily against Candida and Trichophyton, represents a new family of naturally-occurring compounds. Approximately 90% of the antibiotic activity synthesized remained associated with the fungal cell mass, from which it was recovered by multiple methanolic extractions for quantitation. Antibiotic production was enhanced by tryptophan, iron, zinc, and high levels of dextrin.

Determination of the optimal treadmill slope for reproducing the same cardiac response in saddle horses as overground exercise conditions.

The purpose of this study was to define the most suitable treadmill slope for reproducing the same heart rate response as in horses being ridden on a track. Seven French saddle horses were exercised first on a level turf track and then on a treadmill. On the track the exercise test consisted of four periods of three minutes of increasing speeds at the trot and the gallop (96 to 600 m/minute). The treadmill exercise tests consisted of seven steps of increasing slope (0 to 9.6 per cent) at the trot (252 m/minute), followed, after an active recovery period at the walk with a 0 per cent slope, by five steps of increasing slope for two minutes each (0 to 6.3 per cent), at the gallop at 493 m/minute. The mean heart rate at each step of the exercise tests was measured with a heart rate recorder. On the exercise track there was a strong linear relationship (R = 0.89, P < 0.01) between heart rate and speed. The heart rate response of the horses exercised at different speeds and slopes on the treadmill was best fitted (R = 0.96, P < 0.01) by a multilinear model. The optimal treadmill slope was determined by equalizing the equations derived from the two tests: s = -0.001 V + 3.658. It was concluded that the optimal treadmill slope ranged between 3.0 and 3.7 per cent. In order to verify this result, a comparison was made between the heart rate response of the horses during the same incremental exercise test performed on the track and on the treadmill with a 3.5 per cent slope.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of reference standards for adrenal steroids excretion in normal prepuberal children.

An improved method of gas-liquid chromatography (GLC) for routine estimation of adrenal steroids in urine is presented. It was applied to the exploration of steroid output in 120 normal prepuberal children to both sexes aged 3 months-12 years. Urinary data were compared to plasmatic values of adrenal hormones estimated by radio-immuno-assays (RIA). Analysis of the relationships between steroids outputs and bone age revealed that the excretion of cortisol catabolites was expressed by a saturation curve whereas that of delta 4-3 keto androgens catabolites were expressed by geometrical pregression curves; urine dehydroepiandrosterone (DHEA) and plasma DHEA-sulfate showed outbreaks of high values beyond 6 years of age which ruled out all curve fitting attempts. The computation of these relationships allowed to determine the confidence belts of the various regressions which appear as a useful tool to estimate the delayed or accelerated character of adrenal activity in prepuberal childhood. Comparison of the various urinary (GLC) and plasmatic (RIA) parameters enabled us to comment on adrenal puberty.

Proper ventilation improves indoor air quality.

Buildings constructed in the 1970s often achieved energy efficiency at the cost of adequate fresh air, leading to unhealthy working conditions. Through a program of preventive maintenance, inspections and attention to employee concerns, most indoor air-quality problems can be avoided.

[Comparative study of the digestion of a complete food in the pony and the rabbit]. / Etude comparative de la digestion d'un aliment complet chez le poney et le lapin.

A complete pelleted diet (table 1) containing 11 p. 100 of crude protein and 17 p. 100 of cellulose (ADF-lignine according to the method of Van Soest) was distributed to ponies and rabbits. Total digestibilities, partial cumulative digestibilities in different compartments of the digestive tract (stomach, small intestine, caecum, proximal and distal colon) and changes in biochemical composition, measured by pH, VFA, lactic acid and ammonia concentrations, were compared. Total digestibilities (table 2). There was no significant difference in dry matter between the two species. Crude protein digestibility was higher in ponies, but a greater difference was observed for crude fiber digestibility: digestibility in the rabbit was 60 p. 100 of that in the pony. Starch was entirely digested in ponies and rabbits. Partial digestibilities (table 3). The dry matter content was the same in the stomach, the different parts of the small intestine and the caecum of both species. Starch was rapidly digested, but crude protein digestibility was highly negative in the stomach, small intestine and caecum of both species. Changes in biochemical composition (table 4). VFA concentrations were higher in the caecum and colon of ponies but molar percentages of acetic, propionic and butyric acids were very comparable (fig. 1); L-lactic acid concentration was higher in the first part of the digestive tract of ponies and ammonia concentration was lower.

Regulation of SNM1, an inducible Saccharomyces cerevisiae gene required for repair of DNA cross-links.

The interstrand cross-link repair gene SNM1 of Saccharomyces cerevisiae was examined for regulation in response to DNA-damaging agents. Induction of SNM1-lacZ fusions was detected in response to nitrogen mustard, cis-platinum (II) diamine dichloride, UV light, and 8-methoxypsoralen + UVA, but not after heat-shock treatment or incubation with 2-dimethylaminoethylchloride, methylmethane sulfonate or 4-nitroquinoline-N-oxide. The promoter of SNM1 contains a 15 bp motif, which shows homology to the DRE2 box of the RAD2 promoter. Similar motifs have been found in promoter regions of other damage-inducible DNA repair genes. Deletion of this motif results in loss of inducibility of SNM1. Also, a putative negative upstream regulation sequence was found to be responsible for repression of constitutive transcription of SNM1. Surprisingly, no inducibility of SNM1 was found after treatment with DNA-damaging agents in strains without an intact DUN1 gene, while regulation seems unchanged in sad1 mutants.

[The effect of delayed medical consultation on the results of ergotherapy]. / Der Einfluss der ärztlichen Verschleppungszeit auf die Ergebnisse der Ergotherapie.

In connection with 567 patients suffering from finger and metacarpale fractures who were treated conservatively the influence of the delaying time on the ergotherapy with its consequences was investigated, but also the influence of the ergotherapy itself. 80.3% of the patients showed a complete rehabilitation after an immediate beginning of ergotherapy. Only 41.0% of the patients remained without residual defects with the beginning of the ergotherapy after a conservative immobilisation therapy. Similar insufficient results were obtained in the group without ergotherapy (only 51.1%). Though after some years the function at late injuries was improved by the help of training in daily life and by means of work remarkable differences between the ergotherapy group and the collective without ergotherapy are recognizable.

[Establishment of a re-entrant ileo-cecal fistula in Equidae]. / Mise au point d'une fistule iléo-caecale ré-entrante chez les équidés.

A re-entrant cannulation of the digestive tract was performed in Equidae (ponies and donkeys) between the distal extremity of the ileum and the base of the caecum. The operative technique was conceived to avoid risks of infection of the peritoneal cavity: the openings of the ileum and of the caecum were achieved only after the closure of the abdominal wall incision. Two donkeys were still alive ten months after the operation. This method can provide a convenient model for digestibility studies in Equidae, particularly for assessment of the pre-caecal digestibility.