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Biomedical subjects

F Moreno

Publications and source records attributed to F Moreno.

At least 199 records · Page 11Linked to original sources

Morphological and histochemical characteristics of muscle fibre types in the flexor carpi radialis of the dog.

The canine flexor carpi radialis is subdivided into 2 portions. The radial portion which occupies one third of the cross-section is located caudomedially and is composed only of large type I fibres (43.53 +/- 0.6 microns minimum diameter) in levels close to the insertion. The cubital portion is located craniolaterally and contains fewer and smaller type I fibres (26.10 +/- 0.3 microns minimum diameter). It is hypothesised that the radial portion of the muscle, with its larger slow fibre population, contributes to forelimb postural function. The cubital portion, with its generally fast fibre population (IIA), may be more important in the muscle's recognised function (flexion of the carpal joint during locomotion).

Adenosine Triphosphatases↗

Skeletal muscle fibre types in the dog.

Using a variety of histochemical methods we have investigated the mATPase reaction of skeletal muscle fibres in the dog. Types I, IIA, IIDog (peculiar to the dog) and IIC fibres were identified. The results reveal that the interpretation of the fibre type composition depends on the methods used.

Adenosine Triphosphatases↗

[Diagnostic effectiveness of CT and MR in local staging of renal tumors].

The aim of this paper is to study the pre-operative staging of renal tumours, comparing CT and MR, and the imaging criteria used, examining the diagnostic efficacy for each of them. Thirty-four tumours were obtained from 29 patients. All cases were studied with CT and MR. To measure diagnostic efficacy, both for each technique and the criteria used in 2 different readings, a diagnostic performance curve (DPC) is calculated. Neither CT nor MR show infiltration of renal capsule. With regard to perinephritic fat, fascia and adjacent organ invasion, both techniques lead to overstaging, mainly CT. When applying more conservative reading criteria, the results are much improved, specially in relation to CT, although results with MR continue to be more favourable. MR is better to study vascular invasion, providing no false results. Of 22 tumours undergoing surgery, first option was the correct staging in 14 tumour with CT and in 16 with MR. When selecting the best imaging technique to stage renal tumours, MR allows a better and simpler radiologic reading. Nevertheless, considering the high correlation between CT and MR, CT can be used more reliably in institutions where no easy access to a MR unit is available. Both CT and MR overstage renal tumours.

Adult↗

The ICL1 gene from Saccharomyces cerevisiae.

The glyoxylate cycle is essential for the utilization of C2 compounds by the yeast Saccharomyces cerevisiae. Within this cycle, isocitrate lyase catalyzes one of the key reactions. We obtained mutants lacking detectable isocitrate lyase activity, screening for their inability to grow on ethanol. Genetic and biochemical analysis suggested that they carried a defect in the structural gene, ICL1. The mutants were used for the isolation of this gene and it was located on a 3.1-kb BglII-SphI DNA fragment. We then constructed a deletion-substitution mutant in the haploid yeast genome. It did not have any isocitrate lyase activity and lacked the ability to grow on ethanol as the sole carbon source. Both strands of a DNA fragment carrying the gene and its flanking regions were sequenced. An open reading frame of 1671 bp was detected, encoding a protein of 557 amino acids with a calculated molecular mass of 62515 Da. The deduced amino acid sequence shows extensive similarities to genes encoding isocitrate lyases from various organisms. Two putative cAMP-dependent protein-kinase phosphorylation sites may explain the susceptibility of the enzyme to carbon catabolite inactivation.

Amino Acid Sequence↗

Does thrombolysis in myocardial infarction (TIMI) perfusion grade 2 represent a mostly patent artery or a mostly occluded artery? Enzymatic and electrocardiographic evidence from the TEAM-2 study. Second Multicenter Thrombolysis Trial of Eminase in Acute Myocardial Infarction.

One measure of the success of thrombolysis is the early patency status of the infarct-related coronary artery. The Thrombolysis in Myocardial Infarction (TIMI) study group designated patency grades 0 (occluded) or 1 (minimal perfusion) as thrombolysis failure and grade 2 (partial perfusion) or 3 (complete perfusion) as success. To evaluate their true functional significance, perfusion grades were compared with enzymatic and electrocardiographic (ECG) indexes of myocardial infarction in 359 patients treated within 4 h with anistreplase (APSAC) or streptokinase. Serum enzymes and ECGs were assessed serially. Patency was determined at 90 to 240 min (median 2.1 h) and graded by an observer who had no knowledge of patient data. Results for the two drug arms were similar and combined. Distribution of patency was grade 0 = 20%, n = 72; grade 1 = 8% n = 27; grade 2 = 16%, n = 58 and grade 3 = 56%, n = 202. Interventions were performed after angiography but within 24 h in 51% (n = 37), 70% (n = 19), 41% (n = 24) and 14% (n = 28) of patients with grades 0, 1, 2 and 3, respectively. Outcomes were compared among the four patency groups by the orthogonal contrast method. Patients with perfusion grade 2 did not differ significantly from those with grade 0 or 1 in enzymatic peaks, time to peak activity and evolution of summed ST segments, Q waves and R waves (contrast 2). Conversely, comparisons of patients with grade 3 perfusion with those with grades 0 to 2 yielded significant differences for enzymatic peaks and time to peak activity for three of the four enzymes (p = 0.02 to 0.0001) and ECG indexes of myocardial infarction (p = 0.02 to 0.0001) (contrast 3). Thus, patients with grade 2 flow have indexes of myocardial infarction similar to those in patients with an occluded artery (grades 0 and 1 flow). Only early grade 3 flow results in a significantly better outcome than that of the other grades. Because early achievement of grade 2 flow does not appear to lead to optimal myocardial salvage, the frequency of achieving grade 3 perfusion alone may best measure the reperfusion success of thrombolytic therapy.

Anistreplase↗

Genetics of ribosomally synthesized peptide antibiotics.

In recent years many peptide antibiotics have been shown to be ribosomally synthesized. Among these are many microcins, produced by diverse strains of gram-negative bacteria. While the structures and modes of action of these peptide antibiotics vary widely, many of them share several important features. Their synthesis is often induced by the cessation of growth. In addition, many of them undergo unusual posttranslational modifications to yield the mature molecule, which is often exported from the cell by a dedicated export apparatus. The genes involved in modification and export of the peptide antibiotics are generally found adjacent to the structural gene and are under the same regulation. The results supporting these conclusions are reviewed and discussed in this chapter.

Amino Acid Sequence↗

[Transposition of the great arteries. A follow-up of patients operated on with atrial correction].

The late results of 146 patients with transposition of the great arteries (simple: 119, complex: 27) surviving to physiological correction (Mustard: 33, Senning: 113) are analyzed. The mean age at operation was 27 months (1-120), and the mean follow-up was 78 months (6-187). The mean P wave voltage significantly decreased (from 0.3 mV preoperatively to 0.16 mV postoperatively). Frontal mean P wave axis varied from 63.9 degrees to 71.3 degrees. Mean heart rate were significantly lower than those for age-matched normal children. Previous atrioseptectomy had been performed in 36 patients and five of them had arrhythmias before operation. 78 (55%) out of the remaining 141 showed arrhythmias in the surface ECG: sinus node disfunction in 51, tachyarrhythmias in eight, atrioventricular block in eight and several association of arrhythmias in 11. Actuarial survival free of arrhythmias is 81% at the first year, 49% at 5 years and 22% at 15 years. The incidence of arrhythmias in the group of 92 patients with Holter monitoring was higher, with 73 cases having arrhythmias (79%): sinus node disfunction in 47, tachyarrhythmias in ten, atrioventricular block in four and associated in 12. Survival free of arrhythmias by both methods (ECG and Holter) shows a 78% at the first year, 28% at 5 years and 5.6% at 15 years. No significant correlation was found between the incidence of arrhythmias and the type of TGA (simple or complex) or the surgical technique (Mustard or Senning). Permanent pacemakers were implanted in seven to a mean follow-up of 7 years. Five patients were reoperated to a mean follow-up of 46 months. There were 7 late deaths to a mean follow-up of 13 months, four of them being sudden. The actuarial survival rate for the whole group was 93.5% at 15 years. No significant correlation was found between the late mortality and the type of TGA or operation. There was also no correlation with the incidence of arrhythmias. Residual lesions were found in 46 patients, hemodynamically significant in ten. Functional status was class I (NYHA) in 123, and class II in 16. There was correlation between the functional class and the residual lesions.

Age Factors↗

[The 2-chambered right ventricle with an anomalous muscle bundle].

The clinical picture, course, electrocardiogram and chest X-Ray of 30 patients with the angiocardiographic diagnosis of double-chambered right ventricle, along with the echocardiogram in 18 and surgical results in 26 are analyzed. A ventricular septal defect was associated in most of the patients, that had spontaneous closure in some of them. The clinical picture and serial catheterization in some cases suggested progressive obstruction of the right ventricular outflow tract. In this, as in most of the reported series, the history, physical examination, ECG and roentgenogram were inconclusive for diagnosis of this entity. Two-dimensional echocardiography was the most reliable non invasive method to assess this malformation, even superior to catheterization in some aspects. The angiocardiographic findings are quite distinctive, allowing differentiation of other types of subpulmonary stenosis. In order to achieve a good surgical result is essential a precise diagnosis of this malformation and of the associated anomalies. The long-term prognosis was good as in most of the reported series.

Angiocardiography↗

Effects of early thrombolytic therapy (anistreplase versus streptokinase) on enzymatic and electrocardiographic infarct size in acute myocardial infarction. TEAM-2 Investigators.

The effects of thrombolytic therapy on enzymatic and electrocardiographic indexes of myocardial infarction were examined in 370 patients who were enrolled within 4 hours of onset of symptoms and were randomized to blinded therapy with intravenous anistreplase (30 U/5 min, n = 188) or streptokinase (1.5 million IU/1 hour, n = 182). Creatine kinase and its MB isoenzyme were initially measured every 4 to 6 hours, and lactic dehydrogenase (LDH) and its cardiac isoenzyme (LDH-1) every 8 to 12 hours. Electrocardiograms were obtained before, and at 90 minutes and 8 hours after starting thrombolysis, and on discharge. Enzymatic and electrocardiographic measures of infarction were compared between drug treatment and patency groups. Early patency was associated with significant reductions in peak values for each of 4 cardiac enzymes (averaging 21 to 25%, p less than 0.01 to 0.001), even though later rescue procedures were often used in the nonpatient group; times to peaks were also reduced for 3 of the enzymes. Treatment with anistreplase was associated with enzymatic peaks that tended to be lower than with streptokinase (6 to 16%), approaching or reaching significance for LDH (p less than or equal to 0.07) and LDH-1 (p less than or equal to 0.04); times to peaks were similar. Early patency favorably affected electrocardiographic indexes. Summed ST-segment elevations resolved more rapidly (p less than or equal to 0.04), summed Q-wave amplitude was reduced by 32% (p less than or equal to 0.01), and total QRS infarct score on discharge was 22% less (p less than or equal to 0.006) in those achieving early patency. Small differences in electrocardiographic indexes between the 2 drug treatment groups were not significant. These results support use of early reperfusion to reduce infarct size in acute myocardial infarction with administration of streptokinase and anistreplase.

Anistreplase↗

An unusual mechanism for resistance to the antibiotic coumermycin A1.

Bacterial DNA gyrases are type II topoisomerases made up of two A subunits and two B subunits. Coumarins are carbohydrate-containing antibiotics that inhibit topoisomerases II by competing with ATP for binding to the enzymes. High resistance to coumarins is produced in bacterial species by mutations in gyrB, the gene encoding subunit B. We have found an unusual mechanism of resistance to coumarins in Escherichia coli. This mechanism is exhibited by cells containing the wild-type gyrB, or its 5' half, in high copy number. Since homologous mutant gyrB (coumermycin resistant) truncated genes did not confer drug resistance at all under the same conditions, we propose that this mechanism of resistance is due to drug sequestration by the overproduced wild-type GyrB polypeptides. A corollary of this is that the amino half of GyrB is required and sufficient to fashion the ATP-binding domain of DNA gyrase, a conclusion that was further supported by mapping three independent coumarin-resistant mutations at Arg-136 of GyrB. Just upstream of this residue there is a glycine-rich sequence highly conserved in all topoisomerases II, which seems to be a good candidate for the actual ATP-binding site.

Amino Acid Sequence↗

The peptide antibiotic microcin B17 induces double-strand cleavage of DNA mediated by E. coli DNA gyrase.

Microcin B17 (MccB17) is a bactericidal peptide antibiotic which inhibits DNA replication. Two Escherichia coli MccB17 resistant mutants were isolated and the mutations were shown to map to 83 min of the genetic map. Cloning of the mutations and Tn5 insertional analysis demonstrated that they were located inside gyrB. The approximate location of the mutations within gyrB was determined by constructing hybrid genes, as a previous step to sequencing. Both mutations were shown to consist of a single AT----GC transition at position 2251 of the gene, which produces a Trp751----Arg substitution in the amino acid sequence of the GyrB polypeptide. The inhibitory effect of MccB17 on replicative cell-free extracts was assayed. In this in vitro system, interaction of MccB17 with a component of the extracts induced double-strand cleavage of plasmid DNA. In vivo treatment with MccB17 also induced a well-defined cleavage pattern on chromosomal DNA. These effects were not observed with a MccB17-resistant, gyrB mutant. Altogether, our results indicate that MccB17 blocks DNA gyrase by trapping an enzyme-DNA cleavable complex. Thus, the mode of action of this peptide antibiotic resembles that of quinolones and a variety of antitumour drugs currently used in cancer chemotherapy. MccB17 is the first peptide shown to inhibit a type II DNA topoisomerase.

Amino Acid Sequence↗

Mutations in the aphA-2 gene of transposon Tn5 mapping within the regions highly conserved in aminoglycoside-phosphotransferases strongly reduce aminoglycoside resistance.

Aminoglycoside-phosphotransferases contain several conserved amino acid sequence motifs. Using hydroxylamine we have obtained five independent missense mutations within the aphA-2 gene of transposon Tn5. Four of the mutations dramatically reduced antibiotic resistance. Two were identical and included the replacement of His-188 with Tyr. One other resulted from the replacement of Gly-189 with Asp. These three mutations map within the first of the conserved motifs. The replacement of Asp-261 with Asn maps to the third of these structural motifs. A mutation diminishing but not eliminating aminoglycoside resistance resulted from replacement of the conserved Val-36 with Met. By site-directed mutagenesis three additional mutants were obtained: His-188 was replaced with Leu and Ser, and Arg-211 within the second conserved motif was substituted by Gly. All three showed reduced levels of resistance to kanamycin. Our results show that these conserved motifs are essential for the biological activity of aminoglycoside phosphotransferases.

Amino Acid Sequence↗

Nucleotide sequence of the Escherichia coli regulatory gene mprA and construction and characterization of mprA-deficient mutants.

In high copy number, the Escherichia coli mprA gene reduces the synthesis of peptide microcins B17 and C7 (MccB17 and MccC7) and blocks the osmoinduction of the proU operon at the transcriptional level. mprA has been sequenced and shown to encode a polypeptide of 176 amino acids (Mr, 20,563). Insertion and deletion mutant mprA alleles were constructed and then transferred to the chromosome by allelic replacement. In these mutants, expression of two mcb-lacZ fusions was fivefold derepressed, indicating a negative regulatory role of mprA on the mcb operon (MccB17). In contrast, no effect of the MprA- mutations on the expression of mcc operon (MccC7) or on the osmoinduction of proU operon was observed.

Alleles↗