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Biomedical subjects

M Casanova

Publications and source records attributed to M Casanova.

At least 109 records · Page 6Linked to original sources

Formaldehyde concentrations in the blood of rhesus monkeys after inhalation exposure.

The effect of subchronic exposure to formaldehyde (HCHO; 6 ppm; 6 hr/day, 5 days/wk for 4 wk) on the HCHO concentration in the blood of three rhesus monkeys was investigated. Immediately after the final exposure, the monkeys were sedated, and blood samples were withdrawn 7 min after the end of exposure. The HCHO concentration in the blood, determined by gas chromatography-mass spectrometry was 1.84 +/- 0.15 micrograms/g blood and did not differ significantly after a further 45 hr without exposure to HCHO (2.04 +/- 0.40 micrograms/g blood). The average concentration of HCHO in the blood of exposed monkeys was also not significantly different from that of three unexposed controls (2.42 +/- 0.09 micrograms/g blood). However, individual monkeys differed significantly from one another with respect to their blood concentrations of HCHO. These results indicate that subchronic inhalation exposure of non-human primates to HCHO has no significant effect on the HCHO concentration in the blood, and that the average concentration of HCHO in the blood of monkeys is similar to that in the blood of humans.

Administration, Inhalation↗

Residues of EBDC fungicides and ETU in experimental and commercial beverages (beer and wine).

Residues of EBDC (ethylenebisdithiocarbamate) fungicides and ETU (ethylenethiourea; 2-imidazolidinethione) were monitored in beers and wines from different locations. No EBDC residues were detected in any of the samples examined. Concerning the ETU residues, the residue levels higher than the limit of method detection (0.01 ppm) were 22.6% and 7.3% in the commercial beer and wine samples respectively, but the number of samples containing more than 0.1 ppm of ETU was practically negligeable.

Beer↗

Further studies of the metabolic incorporation and covalent binding of inhaled [3H]- and [14C]formaldehyde in Fischer-344 rats: effects of glutathione depletion.

Glutathione (GSH) is required for the oxidation of formaldehyde (HCHO) to formate catalyzed by formaldehyde dehydrogenase (FDH). The effects of GSH depletion on the mechanisms of labeling of macromolecules in the rat nasal mucosa and bone marrow by 3HCHO and H14CHO were investigated. Male rats were exposed for 3 hr to atmospheres containing 3HCHO and H14CHO at concentrations of 0.9, 2, 4, 6, or 10 ppm, 1 day after a single 3-hr preexposure to the same concentration of unlabeled HCHO. Two hours prior to the second exposure, the animals were injected either with phorone (300 mg/kg, ip) or with corn oil. The concentration of nonprotein sulfhydryls in the nasal respiratory mucosa of phorone-injected rats was decreased to 10% of that of corn oil-injected rats. The metabolic incorporation of 3HCHO and H14CHO into DNA, RNA, and proteins in the respiratory and olfactory mucosa and bone marrow (femur) was significantly decreased, and DNA-protein crosslinking was significantly increased in the respiratory mucosa of phorone-injected relative to corn oil-injected rats at all HCHO concentrations. DNA-protein crosslinks were not detected in the respiratory mucosa of corn oil-injected rats at 0.9 ppm. Evidence was obtained for the formation of adducts of HCHO with the RNA from the nasal respiratory mucosa of phorone-injected rats at concentrations above 0.9 ppm. Covalent binding of HCHO to macromolecules in the bone marrow was not detected. These results indicate that the GSH-dependent oxidation of HCHO catalyzed by FDH is an important defense mechanism against the covalent reactions of HCHO with nucleic acids in the respiratory mucosa. Experiments using phorone-injected rats exposed to 10 ppm of [3H]- and [14C]formaldehyde showed that the DNA from the respiratory mucosa was enriched in 3H relative to 14C in comparison to the inhaled vapor. The enrichment is explained by an isotope effect in the oxidation of 3HCHO and H14CHO (H. d'A, Heck and M. Casanova (1987). Toxicol. Appl. Pharmacol. 89, 122-134), which results in 3H enrichment of the residual (unoxidized) HCHO that binds to DNA. A non-linear pharmacokinetic model is proposed that depicts the potential effects of FDH saturation on the relative concentrations of intracellular to extracellular HCHO.

Administration, Inhalation↗

Isotope effects and their implications for the covalent binding of inhaled [3H]- and [14C]formaldehyde in the rat nasal mucosa.

DNA-protein crosslinks were formed in the nasal respiratory mucosa of Fischer-344 rats exposed for 3 hr to selected concentrations of [3H]- and [14C]formaldehyde (3HCHO and H14CHO) (M. Casanova and H. d'A. Heck (1987). Toxicol. Appl. Pharmacol. 89, 105-121). In rats depleted of glutathione (GSH) and exposed to 10 ppm of 3HCHO and H14CHO, the 3H/14C ratio of the fraction of the DNA that was crosslinked to proteins was significantly (39 +/- 6%) higher than that of the inhaled gas. This suggests an isotope effect, either on the formation of DNA-protein crosslinks by labeled HCHO or on the oxidation of labeled HCHO catalyzed by formaldehyde (FDH) or aldehyde dehydrogenase (AldDH). The possibility of an isotope effect on the formation of crosslinks was investigated using rat hepatic nuclei incubated with [3H]- and [14C]formaldehyde (0.1 mM, 37 degrees C). A small (3.4 +/- 0.9%) isotope effect was detected on this reaction, which slightly favored 3HCHO over H14CHO in binding to DNA. The magnitude of this isotope effect cannot account for the high isotope ratio observed in the crosslinked DNA in vivo. The possibility of an isotope effect on the oxidation of 3HCHO and H14CHO catalyzed by FDH was investigated using homogenates of the rat nasal mucosa incubated with [3H]- and [14C]formaldehyde at total formaldehyde concentrations ranging from 0.1 to 11 microM, NAD+ (1 mM), GSH (15 mM), and pyrazole (1 mM). The experiments showed that 3HCHO is oxidized significantly more slowly than H14CHO under these conditions (Vmax/Km (H14CHO) divided by Vmax/Km (3HCHO) = 1.82 +/- 0.11). A similar isotope effect was observed in the absence of GSH, presumably due to the oxidation of 3HCHO and H14CHO catalyzed by AldDH. These results suggest that the residual (unoxidized) formaldehyde present in the nasal mucosa of rats exposed to [3H]- and [14C]formaldehyde may be "enriched" in 3HCHO relative to H14CHO, which can bind to DNA resulting in an isotope ratio higher than that of the inhaled gas. The isotope effect on the oxidation of 3HCHO and H14CHO suggests that previous estimates of the amount of HCHO covalently bound to nasal mucosal DNA (M. Casanova-Schmitz, T. B. Starr, and H. d'A. Heck (1984). Toxicol. Appl. Pharmacol. 76, 26-44) may have been too large, especially at low airborne concentrations and that the shape of the concentration-response curve for DNA-protein crosslinking is more nonlinear than reported previously.

Administration, Inhalation↗

Further cytologic evidence for Xp-Yp translocation in XX males using in situ hybridization with Y-derived probe.

Chromosome preparations from seven subjects with aberrations of sex chromosomes were utilized for in situ hybridization studies with the tritium-labeled Y-derived probe p50f. Two subjects had a pseudodicentric chromosome consisting of two copies of Yp and a portion of Y long arm; two were XX males [46,XX,t(Xp;Yp)], one was missing part of the Y short arm, and another had t(5p;Yq); in addition cells from an XYY male as well as a normal 46,XY male, and a 46,XX female, were hybridized with the same probe. The hybridization technique of Harper and Saunders (1981) was used. There was excess labeling of the Yp/paracentromeric regions in the cases with the normal Y, the XYY, the pseudodicentric Y, and the 5/Y translocation. No significant label was seen on metaphases from the normal 46,XX female or the female with the partially missing Y short arm. Excess label was present on the X short arm in the cases of the XX males; there were 8% and 9.5% of cells with label. The combined cytogenetic and hybridization data indicate that one X short arm in these XX males has undergone a translocation with Yp, and that genes for sex determination probably reside on the distal half of the Y short arm.

Chromosome Banding↗

Differential translational efficiency of the mRNAs isolated from derepressed and glucose repressed Saccharomyces cerevisiae.

Carbon catabolite derepression induced changes in the pool of yeast mRNAs translatable in a protein-synthesizing reticulocyte system. Competition experiments with globin mRNA showed that the mRNA population obtained from derepressed cells possessed a higher translational efficiency than mRNA from repressed cells. The mRNAs that could account for the high translational efficiency of the derepressed mRNA were not detected in cells growing in glucose-rich medium. Analysis of protein synthesis in the presence of 7-methylguanosine 5'-phosphate indicated that the initiation factors recognizing the 5'-terminal structure of capped messengers interacted with lower affinity with the repressed than with some specific derepressed mRNAs.

Enzyme Repression↗

The p12f2/TaqI Y-specific polymorphism in three groups of Italians and in a sample of Senegalese.

The TaqI/p12f2 Y-specific RFLP was studied in 258 Italians (69 from North, 74 from Centre-South and 115 from Southern Sardinia) and in 65 Senegalese. The two allelic fragments of 10 and 8 kb characterizing this polymorphism were both found in the Italians but only the 10 kb band was found among the Senegalese. The observed frequency of the 8 kb allele was 32.4% in Central-Southern Italians, 17.4% in Northern Italians and 13.0% in Southern Sardinians. The last figure is significantly lower than that (34.3%) previously reported for a smaller sample of the same population.

Alleles↗

[XX male syndrome: a study model of the genetic determination of the male sex].

Using Y-specific probes, issued from a library of the human Y chromosome, DNA from about 30 XX men has been studied by the Southern technique. Two groups of patients could be distinguished: one with Y genetic material, the second, without Y DNA. Among XX males with Y sequences there was a genetic heterogeneity with a variable amount of Y DNA sequences. These Y DNA sequences come from the short arm of the Y chromosome and are probably translocated to the paternal X. Concerning the other group, in which no Y sequence could be detected, either Y DNA was present but was not detected, or the mechanism of maleness was Y-independent.

Base Sequence↗

Decreased extractability of DNA from proteins in the rat nasal mucosa after acetaldehyde exposure.

Acetaldehyde and formaldehyde have been found to induce nasal cancer in two species of rodents. To understand the mechanism of carcinogenesis by acetaldehyde, studies were carried out to determine whether acetaldehyde can react with DNA in target tissues of the rat nasal cavity. When fresh homogenates of the nasal respiratory mucosa were incubated with acetaldehyde (distilled under N2) at concentrations of 10, 100, or 500 mM, followed by solubilization and extraction with a strongly denaturing aqueous-immiscible organic solvent mixture, a decrease was observed in the amount of DNA partitioned into the aqueous phase at the two higher acetaldehyde concentrations. The absent DNA was recovered from the interfacial layer by proteolytic digestion. Similarly, incubation of calf thymus nucleohistones with acetaldehyde (100, 300, Similarly, incubation of calf thymus nucleohistones with acetaldehyde (100, 300, or 1000 mM) or with formaldehyde (10, 30, or 100 mM) followed by precipitation of the DNA with H2SO4 and analysis of the supernatants by sodium dodecyl sulfate-polyacrylamide gel electrophoresis resulted in concentration-dependent decreases in the quantities of histone proteins released from the DNA. These results indicate that acetaldehyde as well as formaldehyde can form DNA-protein crosslinks in vitro. A single 6-hr exposure of male Fischer-344 rats to acetaldehyde (100, 300, 1000, or 3000 ppm) resulted in a significant increase relative to air-exposed controls in the percent interfacial DNA from the nasal respiratory mucosa at concentrations equal to or greater than 1000 ppm. No increase in the interfacial DNA from the olfactory mucosa was detected after a single 6-hr exposure (1000 or 3000 ppm), but a significant increase was found in rats hr/day for 5 days) to acetaldehyde (1000 ppm). Thus, evidence has been obtained hr/day for 5 days) to acetaldehyde (1000 ppm). Thus, evidence has been obtained for the formation of DNA-protein crosslinks by acetaldehyde in target tissues of the rat nasal cavity at concentrations similar to those that induced nasal cancer.

Acetaldehyde↗

Small deletions of the short arm of the Y chromosome in 46,XY females.

Structural anomalies of the sex chromosomes provide a means to study the location of genes responsible for sex determination. Recently, a type of sex reversal in humans, the 46,XX male, was shown to result in some cases from translocation of Y chromosome material to the X chromosome. In the present report, another type of sex reversal, the 46,XY female, is shown to result, in two cases, from small deletions of the short arm of the Y chromosome. Prometaphase chromosome analysis showed a 46,X,Yp- karyotype. Several Y chromosome-specific DNA probes were found to be deleted in the two female patients. DNA analysis showed that the two deletions were different but included a common overlapping region likely to be essential for male determination.

Chromosome Deletion↗

[Acute pancreatitis. Our experience].

Between the years 1975 and 1984, 228 patients with acute pancreatitis (A.P.) have been studied at the "A. Posadas Hospital". The diagnosis was confirmed in 212 patients by surgery, in the remaining 16 by clinical evaluation, increase in the activity of serum or peritoneal fluid amylase, ultra-sonography and computed tomography. The sex distribution was: female 151 (66.2%) male 77 (33.8%), the mean age in each group was 42.9 and 45 years respectively. The etiologic factors were: biliary tract disease 178 (78%) alcohol 24 (10.5%) idiopathic 16 (7%) others factors 10 (4.4%). We found mild and moderate forms of the illness in 179 (78.5%) and severe form in 49 (21.5%) patients. The mortality rate of the whole group was 29 (12.7%) and according to the etiology it was, in the biliary group 20 (11.2%) alcoholic 4 (16.6%) idiopathic 3 (18.7%). The mortality in the mild and moderate forms was 5% and 40.8% in the severe forms. The patients who underwent surgery were classified in three groups according to the opportunity of surgical treatment: elective surgery, early surgery, surgery for complications. There was no mortality in the elective surgery group. The patients operated on early period had a mortality of 18.75% (21 pts.) whereas those operated due to complications had a mortality of 42.1% (8 pts.). According to the above mentioned experience we consider that a patient with an A.P. must be classified with the known indexes in mild or severe forms, at the same time one should study the actual etiologic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Complications of decompression of the internal ear during diving].

Inner ear decompression sickness belongs inner ear barotrauma. It occurs after a dive with factors of risk. The diagnostic needs an accurate history and physical examination which allows emergency treatment: therapeutic recompression, then hyperbaric oxygen and perfusions of vasodilators + corticoids. The symptomatology is mainly vestibular and the discussion between peripheric and/or central lesions is still open.

Adult↗

A human Y-linked DNA polymorphism and its potential for estimating genetic and evolutionary distance.

A human DNA sequence (p12f2), derived from a partial Y-chromosome genomic library and showing homology with the X and Y chromosomes and with an undetermined number of autosomes, detected two Y-specific restriction fragment length variants on male DNA that had been digested with Taq I and Eco RI. These variants may have been generated through a deletion-insertion mechanism and their pattern of holoandric transmission indicates that they represent a two-allele Y-linked polymorphism (RFLP). By means of DNA from patients with inborn deletions in chromosome Y, this polymorphic DNA site was mapped to the interval Yq11.1-Yq11.22. The frequency of the rarest allele was about 35 percent in Algerian and Sardinian human males, whereas it was only 4 percent among Northern Europeans. The p12f2 probe also detected Y-specific DNA fragments in the gorilla and chimpanzee. In view of the monosomy of the Y chromosome in mammalian species, Y-linked RFLP's may prove to be more useful than autosomal or X-linked markers in estimating genetic distances within and between species.

Base Sequence↗

[Cardiorespirography of the newborn infant at 12 hours of life].

The introduction of the cardiorespirogram more than twenty years ago provided a useful continous noninvasive monitoring technique of heart and respiratory functions. However, there are only few studies about recording of these parameters and the topic is often partially discussed. Thus, the aim of this paper is to analyze the cardiorespirograms from newborn infants, divided into three groups: 50 normal fullterm infants, 28 preterm and 16 fullterm low birth weight infants. The age at monitoring was 12 hours. The 50 normal newborns reveal patterns similar to those described by other authors. The preterm and fullterm low birth weight infants show a significantly higher baseline with less variability and reactivity, data which lead us to bear in mind gestational age and birth weight to evaluate the cardiorespirogram.

Heart Rate↗

Depletion of nasal mucosal glutathione by acrolein and enhancement of formaldehyde-induced DNA-protein cross-linking by simultaneous exposure to acrolein.

Incubation of homogenates of rat nasal mucosa with acrolein resulted in the apparent formation of DNA-protein cross-links. However, inhalation exposure of male Fischer-344 rats to acrolein (2.0 ppm, 6 h) did not cause detectable DNA-protein cross-linking in the nasal respiratory mucosa. Simultaneous exposure of rats to both acrolein (2.0 ppm) and formaldehyde (6.0 ppm) for 6 h resulted in a significantly higher yield of DNA-protein cross-links than was obtained following exposure to formaldehyde (6.0 ppm) alone. Acrolein exposure at concentrations of 0.1, 0.5, 1.0, or 2.5 ppm resulted in a concentration-dependent depletion of nonprotein sulfhydryl groups in the nasal respiratory mucosa. A plausible explanation for the enhancement of DNA-protein cross-links by simultaneous exposure to formaldehyde and acrolein may be that depletion of glutathione by acrolein inhibited the oxidative metabolism of formaldehyde, leading to an increase of formaldehyde-induced DNA-protein cross-links.

Acrolein↗

[Normal male phenotype or hypospadias and female karyotype. XX male syndrome in children and adolescents].

A morphologically normal 46 XX karyotype has been found in 8 patients with male phenotype, either normal (3 cases) or hypospadiac (5 cases) studied at age 1 month to 15 years. Five had cryptorchidism. Pubertal follow-up was obtained in 6 patients and showed that they had hypogonadism with small testes, and a mean adult height of 163 cm. The hormonal investigations gave normal results before puberty, then after the onset of puberty a hypergonadotropic hypogonadism. Testicular biopsy showed alterations from age 8 years. Studies using Y-specific probes in 3 patients have shown the presence of Y genetic material in 2 and absence in 1, thus demonstrating genetic heterogeneity of the XX males.

Adolescent↗