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Biomedical subjects

M Nadal

Publications and source records attributed to M Nadal.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Renal vascular lesion and microangiopathic hemolytic anemia in systemic lupus erythematosus].

A 22 year-old woman with a seven year history of (SLE) was readmitted because of oliguria, edema, dyspnea and arterial hypertension. She had a previous biopsy diagnosis of focal glomerulonephritis, (WHO III b), and had been treated with immunosuppressors and steroids. Laboratory data showed lupus activity, AHM with thrombocytopenia, nephrotic-range proteinuria and renal failure. A second renal biopsy was performed showing diffuse proliferative nephritis, (WHO IV), in association with noninflammatory necrotizing vasculopathy with luminal obliteration. She started with hemodialysis and was subsequently treated with methylprednisolone pulses, plasmapheresis, cyclophosphamide and oral steroids. During the inpatient period, she had generalized seizures, acute lung injury and pulmonary hemorrhage. These complications, the AHM and the thrombocytopenia receded totally. Renal function was never resumed. We emphasize that this association of diffuse proliferative nephritis with noninflammatory necrotizing vasculopathy is not infrequent and has a poor renal prognosis. The AHM with thrombocytopenia was interpreted as secondary to endothelial cell damage due to vasculopathy.

Adult↗
PubMed1996

Reverse gyrase gene from Sulfolobus shibatae B12: gene structure, transcription unit and comparative sequence analysis of the two domains.

We cloned and sequenced a DNA fragment from the thermophilic archaeal strain Sulfolobus shibatae B12 that includes the gene topR encoding the reverse gyrase. The RNA of the reverse gyrase gene was characterized indicating that the topR gene is fully functional in vivo. We showed by primer extension analysis that transcription of topR initiates 28 bp downstream from a consensus A-box promoter. In order to understand how this particular type I DNA topoisomerase introduces positive superturns into the DNA, we compared the amino acid sequence of reverse gyrase from S.shibatae with the two other known reverse gyrases. This comparison indicates a common organization of these proteins: the carboxy-terminal domain is related to the type I-5' topoisomerase family while the amino-terminal domain possesses some motifs of proteins described as RNA or DNA helicases. By using local alignments, we showed that (i) reverse gyrases constitute a new and rather homogenous group within the type I-5' DNA topoisomerase family; (ii) a careful sequence analysis of the amino-terminal domain allows us to relate the presence of some motifs with an ATP binding and hydrolysis reaction coupled to a DNA binding and unwinding activity.

Adenosine Triphosphate↗
PubMed1996

YAC and cosmid FISH mapping of an unbalanced chromosomal translocation causing partial trisomy 21 and Down syndrome.

Most cases of Down syndrome (DS) result from a supernumerary chromosome 21; however, there are rare cases in which DS is due to partial trisomy of chromosome 21, involving various segments of the chromosome. The characterization of cases of DS that are due to partial trisomy 21 allows the phenotype to be correlated with the genotype. We present a case with features of DS and a partial trisomy of chromosome 21 inherited from a paternal balanced translocation involving chromosomes 13 and 21. Fluorescence in situ hybridization analysis using yeast artificial chromosome (YAC) probes mapped the breakpoint to 21q22.1, within YAC 230E8, which contains markers CBR, D21S333 and D21S334. Further mapping using cosmids positioned the breakpoint proximal to CBR. The patient was also monosomic for the distal portion of chromosome 13 (q33-qter). Many phenotypic features of DS were present including hypotonia, flat occiput, flat facies, up-slanted palpebral fissures, epicanthic folds, flat nasal bridge, macroglossia, open mouth, small ears and a heart murmur. This case further supports the contention that the majority of the phenotypic features of DS map to 21q22-qter and further refines the location of some of them. In addition to the DS phenotype, the patient had a prominent upper maxilla with protruding upper incisors, and low levels of the coagulation factors VII and X, consistent with a syndrome resulting from monosomy 13q33-qter. Since some features overlap between the two syndromes, including severe mental retardation, it is unclear to what extent monosmy for 13q33-qter, trisomy for 21q22.1-qter, or a combination of both, contributed to the common features of the phenotype.

Adult↗
PubMed1996

Secretory rhythm of vasopressin in healthy subjects with inversed sleep--wake cycle: evidence for the existence of an intrinsic regulation.

The objective of this paper was to find out if the higher night levels of vasopressin described in previous studies are a manifestation of a permanent and stable rhythm bound to the different periods of the day or if they are independent of them and due to other causes. Vasopressin secretion was studied in a group of seven healthy subjects with an inverted sleep--wake cycle (night workers who sleep and rest during the day). The study was performed during the last week of their working period after at least 3 weeks of continuous night shift. Plasma samples for vasopressin determination were taken every 4 h during a 24-h period while the subjects were performing their normal night work and with their usual sleeping habits during the day. Plasma osmolality, electrolytes and blood pressure were also assessed during the test. In contrast to previous studies where higher nocturnal values have been reported, we found significantly higher vasopressin levels during the day, giving as a whole a characteristic pattern with the highest vasopressin levels measured at 16.00 h followed by a progressive decrement that reached its nadir at 04.00 h. The total measured secretion of vasopressin was significantly higher during the day than during the night (p = 0.0313). No significant difference was found, on the other hand, between day samples, with the exception of samples taken at 16.00 h and at 12.00 h (p = 0.031). Plasma osmolality and electrolytes were within the normal range during the test and no statistical difference was observed at the various points. It was concluded that the secretion of vasopressin is higher during sleep and rest time and lower during the active part of the 24 h. The secretory pattern of vasopressin is not bound to the different periods of the day as such, nor to variations in plasma osmolality or electrolytes. It seems therefore reasonable to assume that the secretion of vasopressin has an intrinsic daily rhythm that is not related to known regulatory agents but is modulated by other unidentified factors. Several hypotheses are discussed.

Activity Cycles↗
PubMed1995

Assignment of the gene responsible for cystinuria (rBAT) and of markers D2S119 and D2S177 to 2p16 by fluorescence in situ hybridization.

We have established rBAT (named as SLC3A1 in the Genome Data Base) as a gene responsible for cystinuria, a heritable disorder of amino acid transport. The cystinuria locus has been mapped by linkage between microsatellite markers D2S119 and D2S177. Fluorescence in situ hybridization (FISH) either with Alu-polymerase-chain-reaction (PCR)-amplified sequences of a yeast artificial chromosome (YAC) containing the rBAT gene or with rBAT-specific PCR-amplified genomic fragments, and chromosome G-banding have cytogenetically mapped rBAT to 2p16.3. In order to correlate the physical and genetic information on cystinuria, we have performed FISH with combinations of Alu-PCR-amplified sequences from YACs containing rBAT or the D2S119 and D2S177 loci. In all cases, a fused signal is obtained that demonstrates their close physical location; this allows the assignment of rBAT, cystinuria and their linked markers, D2S119 and D2S177, to 2p16.

Amino Acid Transport Systems, Basic↗
PubMed1994

Purification and characterization of reverse gyrase from Sulfolobus shibatae. Its proteolytic product appears as an ATP-independent topoisomerase.

Sulfolobus shibatae B12 is a thermophilic archaebacterium that contains an inducible virus named SSV1. The viral DNA has been shown to be positively supercoiled before encapsidation. We have previously purified an archaebacterial DNA topoisomerase from Sulfolobus acidocaldarius DSM 639, reverse gyrase, likely responsible for this positive supercoiling reaction. In order to study an homogeneous system containing both reverse gyrase and one of its preferential substrate, SSV1 DNA, we have purified this enzyme from S. shibatae. During the course of the purification, we have detected another topoisomerase activity. In order to separate and purify these two topoisomerases, we have devised a new purification procedure. Purified S. shibatae reverse gyrase is a 124-kDa monomer, with a Stokes radius of 43 A and a sedimentation coefficient of 6.2 S. It is able to perform a DNA reverse gyration per se at 10 mM NaCl in a Mg- and ATP-dependent manner. The other topoisomerase is a monomer of about 40 kDa, with a Stokes radius of 25 A and a sedimentation coefficient of 4 S. This additional topoisomerase activity is Mg-dependent and ATP-independent and catalyzes only a relaxation reaction of negatively supercoiled DNA at 150 mM NaCl. This new ATP-independent topoisomerase activity seems to be a proteolysis product of reverse gyrase.

Adenosine Triphosphate↗
PubMed1994

Secretory pattern of vasopressin in plasma and cerebrospinal fluid of patients with dementia and of two control groups.

Since the description of its antidiuretic effect in 1913, a variety of functions have been attributed to vasopressin, one of the most controversial throughout the years probably being its effect on memory processes. In an attempt to study the actual secretory rhythm of vasopressin in humans with demonstrated impaired memory, the plasma and cerebrospinal fluid levels of the peptide have been examined during 24 h in a group of patients with dementia, and their values compared with two healthy control groups of young and elderly volunteers. Patients with dementia had higher circulating levels of vasopressin in plasma than the healthy participants and the differences were statistically significant when compared with the healthy elderly (p = 0.003). This difference is not age-related because both groups were in the same age range. A possible explanation could be the higher plasma osmolality measured in the patients with dementia, despite the fact that their levels were within the normal ranges. The different results could not be attributed to changes in electrolytes or blood pressure because these parameters were similar in all groups (p = NS). But more interesting, perhaps, is the secretory pattern found in all three groups. The pattern is biphasic, with two significant peaks: at 16.00 h (p = 0.032) and at night (p = 0.002). This pattern was similar in all cases and in all groups. The total nocturnal secretion of vasopressin is higher than the diurnal secretion (p = 0.02) only in the plasma because the cerebrospinal fluid values were higher during the day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Once hypertensive, always hypertensive? A three year follow-up after stopping medication.

OBJECTIVE: To verify the existence of hypertension in a group of long-term pharmacologically treated hypertensives and to evaluate the possibility of discontinuing their medication. DESIGN: The diagnosis of hypertension was established when after a wash-out period (one month) the blood pressure measured at three consecutive examinations, with at least one week interval between them, was always higher than WHO's reference levels for the diagnosis of hypertension. Those who did not fulfil these criteria would continue, with regular controls, without medication as long as clinically indicated. The final evaluation was done after a three year follow-up. SETTING: The out-patient Hypertensive Unit of the Department of Geriatrics, Skellefteå Hospital, Sweden. PARTICIPANTS: 86 out-patients (33 males and 53 females) aged 68 to 82 years (mean 74) with long-term hypertension sent to our unit by general practitioners in our health district (population 80,000). RESULTS: 34 of the initial 86 patients required medication by the end of the wash-out period. The remaining 52, 16 males and 36 females, continued without medication and after the three year follow up 14 of them were still without it. There was a striking difference between males and females since a significantly higher number of males than females were free of medication at the end of the period (p < 0.001). In those who restarted pharmacological therapy, the period without medication lasted no longer than five months. CONCLUSIONS: Arterial hypertension can easily be over-represented as a diagnosis if not revised when clinically advisable or if established without accurate criteria. The possibility of stopping the antihypertensive medication in old patients is worth considering, particularly in male patients. The dangers of such strategy are practically minimal when regular controls are undertaken during the attempt.

Aged↗
PubMed1993

Reverse gyrase: a helicase-like domain and a type I topoisomerase in the same polypeptide.

Reverse gyrase is a type I DNA topoisomerase able to positively supercoil DNA and is found in thermophilic archaebacteria and eubacteria. The gene coding for this protein was cloned from Sulfolobus acidocaldarius DSM 639. Analysis of the 1247-amino acid sequence and comparison of it with available sequence data suggest that reverse gyrase is constituted of two distinct domains: (i) a C-terminal domain of approximately 630 amino acids clearly related to eubacterial topoisomerase I (Escherichia coli topA and topB gene products) and to Saccharomyces cerevisiae top3; (ii) an N-terminal domain without any similarity to other known topoisomerases but containing several helicase motifs, including an ATP-binding site. These results are consistent with those from our previous mechanistic studies of reverse gyrase and suggest a model in which positive supercoiling is driven by the concerted action of helicase and topoisomerase in the same polypeptide: this constitutes an example of a composite gene formed by a helicase domain and a topoisomerase domain.

Amino Acid Sequence↗
PubMed1990

Reverse gyrase, a hallmark of the hyperthermophilic archaebacteria.

Investigation of the presence of a reverse gyrase-like activity in archaebacteria revealed wide distribution of this activity in hyperthermophilic species, including methanogens and sulfur-dependent organisms. In contrast, no reverse gyrase activity was detected in mesophilic and moderately thermophilic organisms, which exhibited only an ATP-independent activity of DNA relaxation. These results suggest that the presence of reverse gyrase in archaebacteria is tightly linked to the high growth temperatures of these organisms. With respect to antigenic properties, the enzyme appeared similar among members of the genus Sulfolobus. In contrast, no close antigenic relatedness was found between the reverse gyrase of members of the order Sulfolobales and that of the other hyperthermophilic organisms.

Adenosine Triphosphate↗
PubMed1989

Reverse gyrase binding to DNA alters the double helix structure and produces single-strand cleavage in the absence of ATP.

Stoichiometric amounts of pure reverse gyrase, a type I topoisomerase from the archaebacterium Sulfolobus acidocaldarius were incubated at 75 degrees C with circular DNA containing a single-chain scission. After covalent closure by a thermophilic ligase and removal of bound protein molecules, negatively supercoiled DNA was produced. This finding, obtained in the absence of ATP, contrasts with the ATP-dependent positive supercoiling catalyzed by reverse gyrase and is interpreted as the result of enzyme binding to DNA at high temperature. Another consequence of reverse gyrase stoichiometric binding to DNA is the formation of a cleavable complex which results in the production of single-strand breaks in the presence of detergent. Like eubacterial type I topoisomerase (protein omega), reverse gyrase is tightly attached to the 5' termini of the cleaved DNA. In the light of these results, a comparison is tentatively made between reverse gyrase and the eubacterial type I (omega) and type II (gyrase) topoisomerases.

Adenosine Triphosphate↗
PubMed1988

Reverse gyrase of Sulfolobus: purification to homogeneity and characterization.

By using hydrophobic interaction as the first chromatographic stage, we purified to homogeneity reverse gyrase, an ATP-dependent DNA topoisomerase I, isolated from the thermoacidophilic archaebacterium Sulfolobus acidocaldrius. This procedure allowed quick and complete separation of reverse gyrase from nucleases and DNA binding proteins present in Sulfolobus. The final product was revealed, by SDS-PAGE, as a unique band with an apparent molecular mass of 128 kDa, and the amino acid composition was determined. Western blotting experiments with antibodies raised against reverse gyrase indicate that no proteolysis occurred during the purification course. Gel filtration and sedimentation data gave a Stokes radius of 42 A and a sedimentation coefficient of 5.7 S, suggesting a monomeric structure for the native enzyme which was confirmed by electron microscopy. Finally, pure reverse gyrase in a monomeric state was still able to promote positive supercoiling of the DNA.

Adenosine Triphosphate↗
PubMed1985

High positive supercoiling in vitro catalyzed by an ATP and polyethylene glycol-stimulated topoisomerase from Sulfolobus acidocaldarius.

A topoisomerase able to introduce positive supercoils in a closed circular DNA, has been isolated from the archaebacterium Sulfolobus acidocaldarius. This enzyme, fully active at 75 degrees C, performed in vitro positive supercoiling either from negatively supercoiled, or from relaxed DNA in a catalytic reaction. In the presence of polyethylene glycol (PEG 6000), this reaction became very fast and highly processive, and the product was positively supercoiled DNA with a high superhelical density (form I+). Very low (5 - 10 micromoles) ATP concentrations were sufficient to support full supercoiling; the nonhydrolyzable analogue adenosine-5' -0-(3-thiotriphosphate) also sustained the production of positive supercoils, but to a lesser extent, suggesting that ATP hydrolysis was necessary for efficient activity. Nevertheless, low residual of positive supercoiling occurred, even in the absence of ATP, when the substrate was negatively supercoiled. Finally, the different ATP-driven topoisomerizations observed, i.e., relaxation of negative supercoils and positive supercoiling, in all cases increased the linking number of DNA in steps of 1, suggesting the action of a type I, rather than a type II topoisomerase.=

Adenosine Triphosphate↗
PubMed1985

[Comparison of two skin antiseptics in blood transfusion. Comparison with the results of the bacteriologic control of labile blood products].

The comparison of two skin antiseptics (70 degrees alcohol and 0,5% alcoholic chlorhexidine solution) was carried out by the method of in vivo impressions. The study used 45 healthy volonteers from whom a bacteriological sample was taken from both bends of the elbow, without use of an antiseptic, and after the application of one according to usual sample taking methods. The subjects were divided into two sets according to the antiseptic being tested. The results of the cultures after 24 and 48 hours are expressed in the number of germs per cm2, which thus permits us to calculate a reduction in percentage or log 10 form, and to appreciate the efficiency of the antiseptic studied. Routine bacteriological inspection of labile blood products was carried out on products picked at random every week during 18 months of exclusive use of 70 degrees alcohol by the sample taking services. The results show a comparable in vivo effectiveness of the two antiseptics on the superficial aerobic flora of the bend of the elbow, and the ease of use of 70 degrees alcohol has led to its choice. This choice is confronted with the results of the inspection of blood products: out of 1 293 inspections, only one slight contamination (cocci gram+) was found on a unit of whole blood. These data as a whole can be compared with the work of various authors.

Anti-Infective Agents, Local↗
PubMed1981

[Technical, immunological and clinical study of the performance of blood filtration using Erypur filters].

Technical, immunological and clinical parameters of blood filtration through Erypur filters were evaluated. Red cell concentrates from which the buffy coat had not been eliminated were used throughout the study. Filtration procedure is fully automated, simple and takes about 15 minutes. 98% of leukocytes and 96% of platelets were found to be retained by the filter. Residual leukocytes were less than 3.10(7) in 68% and residual platelets less than 1.10(10) in 93% of filtered units. The incidence of lymphocyte alloantibody formation was 14.9% in the group of 67 patients who received 210 filtered units and 27.9% in the control group of 93 patients who were transfused with 298 non-filtered units. 330 filtered units were transfused to 107 carefully monitored patients and caused no reaction. 40 of these patients had polyspecific HLA antibodies and/or a documented history of non-hemolytic transfusion reactions. The clinical usefulness of Erypur filtered blood in the prevention of such reactions may thus be confirmed.

Blood↗
PubMed1981

Glucose tolerance following oral salbutamol treatment in late pregnancy.

Previous studies in pregnancy have shown that intravenous infusion of beta 2-sympathomimetic drugs, such as salbutamol, is followed by pronounced carbohydrate and lipid metabolic effects. Similar effects, though less pronounced, have also been demonstrated after oral salbutamol administration. Glucose elimination and insulin response after an intravenous glucose tolerance test (IVGTT) were analyzed in 12 women treated with oral salbutamol in the last trimester of pregnancy. IVGTT was performed without salbutamol and after at least 10 and up to 45 days of salbutamol treatment. No significant difference in either glucose elimination or insulin response to the glucose load were observed as a consequence of the salbutamol medication. This is in agreement with previous studies of other beta 2-sympathomimetic drugs and indicates that the use of salbutamol in late pregnancy does not give rise to serious disturbances of carbohydrate metabolism in healthy women.

Adult↗