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Biomedical subjects

A Gabriel

Publications and source records attributed to A Gabriel.

At least 73 records · Page 4Linked to original sources

Rapid temperature changes induce adenosine-mediated depression of synaptic transmission in hippocampal slices from rats (non-hibernators) but not in slices from golden hamsters (hibernators).

Disturbances in neuronal communication induced by rapid temperature changes are a risk in the context of accidental hypothermia and would be fatal for hibernators during arousal from hibernation. Therefore, we investigated the effects of rapid temperature changes on synaptically induced CA1 population spikes in hippocampal slices from golden hamsters (hibernators) and rats (non-hibernators). Temperature was changed ramp-like by 0.3 degrees C/min, which corresponds to the rise of body temperature in golden hamsters during arousal from hibernation. During cooling from 35 to 10-15 degrees C, the population spike amplitude increased, reached maximal values at 25-30 degrees C and 20-25 degrees C in hamster and rat slices, respectively, and then decreased with further cooling. During rewarming, hamster slices displayed the same temperature dependence as during cooling. In contrast, in rat slices dynamic effects of the temperature change occurred. These were most obvious in a strong depression of the spike amplitude during rewarming as compared to cooling. Above 26-29 degrees C, the depression was superimposed by an excitatory effect. The depression was largely attenuated by theophylline (100-200 microM) and thus seems to be based on an increase of the concentration of endogenous adenosine, which in turn may result from an imbalance in energy metabolism during warming. The lack of warming-related depression in hamster slices can be explained by a lower sensitivity for adenosine as compared to rat slices. In addition, a better resistance of metabolic balance against rapid temperature changes may prevent large elevations of endogenous adenosine in the hamster hippocampus. For hibernators, the avoidance of temperature change-induced disturbances of neuronal communication may be a prerequisite for safe arousal from hibernation.

Acclimatization↗

Morphometric study of the equine navicular bone: variations with breeds and types of horse and influence of exercise.

Navicular bones from the 4 limbs of 95 horses, classified in 9 categories, were studied. The anatomical bases were established for the morphometry of the navicular bone and its variations according to the category of horse, after corrections were made for front or rear limb, sex, weight, size and age. In ponies, navicular bone measurements were smallest for light ponies and regularly increased with body size, but in horses, navicular bone dimensions were smallest for the athletic halfbred, intermediate for draft horse, thoroughbreds and sedentary halfbreds and largest for heavy halfbreds. The athletic halfbred thus showed reduced bone dimensions when compared with other horse types. Navicular bones from 61 horses were studied histomorphometrically. Light horses and ponies possessed larger amounts of cancellous bone and less cortical bone. Draft horses and heavy ponies showed marked thickening of cortical bone with minimum intracortical porosity, and a decrease in marrow spaces associated with more trabecular bone. Two distinct zones were observed for the flexor surface cortex: an external zone composed mainly of poorly remodelled lamellar bone, disposed in a distoproximal oblique direction, and an internal zone composed mainly of secondary bone, with a lateromedial direction for haversian canals. Flexor cortex external zone tended to be smaller for heavy ponies than for the light ponies. It was the opposite for horses, with the largest amount of external zone registered for draft horses. In athletic horses, we observed an increase in the amount of cortical bone at the expense of cancellous bone which could be the result of reduced resorption and increased formation at the corticoendosteal junction. Cancellous bone was reduced for the athletic horses but the number of trabeculae and their specific surfaces were larger. Increased bone formation and reduced resorption could also account for these differences.

Animals↗

High-dose recombinant human erythropoietin stimulates reticulocyte production in patients with multiple organ dysfunction syndrome.

OBJECTIVE: To investigate erythropoietin (EPO) production and the erythropoietic potency of recombinant human EPO in the multiple organ dysfunction syndrome. DESIGN: Randomized, prospective, controlled clinical trial. MATERIALS AND METHODS: Patients received either 600 IU/kg intravenous EPO three times weekly (n = 9) or saline (control, n = 10). MEASUREMENTS: EPO levels, circulating soluble receptors for tumor necrosis factor and interleukin-2, levels of interleukin-6 and intercellular adhesion molecule, and early peripheral blood cell progenitors. RESULTS: EPO production in the control group remained low. Pharmacologic EPO blood levels were associated with increased reticulocyte counts compared with both controls (p < 0.04) and baseline (p < 0.006). Increased levels of soluble receptors for tumor necrosis factor in the treatment group compared with the controls did not prevent this effect. Interleukin 6 inhibited reticulocyte production. CONCLUSION: Despite increased cytokine levels, pharmacologic EPO blood levels were associated with increased reticulocyte counts in patients with multiple organ dysfunction syndrome.

Cytokines↗

Transposable elements and genome organization: a comprehensive survey of retrotransposons revealed by the complete Saccharomyces cerevisiae genome sequence.

We conducted a genome-wide survey of Saccharomyces cerevisiae retrotransposons and identified a total of 331 insertions, including 217 Ty1, 34 Ty2, 41 Ty3, 32 Ty4, and 7 Ty5 elements. Eighty-five percent of insertions were solo long terminal repeats (LTRs) or LTR fragments. Overall, retrotransposon sequences constitute >377 kb or 3.1% of the genome. Independent evolution of retrotransposon sequences was evidenced by the identification of a single-base pair insertion/deletion that distinguishes the highly similar Ty1 and Ty2 LTRs and the identification of a distinct Ty1 subfamily (Ty1'). Whereas Ty1, Ty2, and Ty5 LTRs displayed a broad range of sequence diversity (typically ranging from 70%-99% identity), Ty3 and Ty4 LTRs were highly similar within each element family (most sharing >96% nucleotide identity). Therefore, Ty3 and Ty4 may be more recent additions to the S. cerevisiae genome and perhaps entered through horizontal transfer or past polyploidization events. Distribution of Ty elements is distinctly nonrandom: 90% of Ty1, 82% of Ty2, 95% of Ty3, and 88% of Ty4 insertions were found within 750 bases of tRNA genes or other genes transcribed by RNA polymerase III. tRNA genes are the principle determinant of retrotransposon distribution, and there is, on average, 1.2 insertions per tRNA gene. Evidence for recombination was found near many Ty elements, particularly those not associated with tRNA gene targets. For these insertions, 5'- and 3'-flanking sequences were often duplicated and rearranged among multiple chromosomes, indicating that recombination between retrotransposons can influence genome organization. S. cerevisiae offers the first opportunity to view organizational and evolutionary trends among retrotransposons at the genome level, and we hope our compiled data will serve as a starting point for further investigation and for comparison to other, more complex genomes.

Base Sequence↗

In vivo Ty1 reverse transcription can generate replication intermediates with untidy ends.

Ty1 retrotransposition, like retroviral replication, is a complex series of events requiring reverse transcription of an RNA intermediate, RNA-primed minus- and plus-strand DNA synthesis, multiple strand transfers, and precise cleavages of the template and primers by RNase H. In this report, we examine the structure of in vivo Ty1 replication intermediates, specifically with regard to the behavior of reverse transcriptase upon reaching template ends and to the precision with which RNase H might generate these ends. While the expected 3' termini were always identified, terminal nontemplated bases were also observed at all of the RNA and DNA template ends examined. Nontemplated A residues were most common at all 3' ends, although C residues were preferentially added to minus-strand termini paused at the 5' end of capped Ty1 RNA. In addition, we observed that RNase H removal of the tRNA primer and of the polypurine tract was not always precise or efficient. Finally, we noted numerous instances of Ty1 reverse transcriptase transferring from normal Ty1 template ends to various tRNA templates, with continued synthesis to specific modified bases. A similar pattern was obtained for Ty2, indicating that template ends offer unique opportunities for these two related reverse transcriptases to generate errors.

Base Composition↗

Replication errors during in vivo Ty1 transposition are linked to heterogeneous RNase H cleavage sites.

We previously identified a mutational hotspot upstream of the Ty1 U5-primer binding site (PBS) border and proposed a novel mechanism to account for this phenomenon during Ty1 replication. In this report, we verify key points of our model and show that in vivo RNase H cleavage of Ty1 RNA during minus-strand strong-stop synthesis creates heterogeneous 5' RNA ends. The preferred cleavage sites closest to the PBS are 6 and 3 bases upstream of the U5-PBS border. Minus-strand cDNA synthesis terminates at multiple sites determined by RNase H cleavage, and DNA intermediates frequently contain 3'-terminal sequence changes at or near their template ends. These data indicate that nontemplated terminal base addition during reverse transcription is a real in vivo phenomenon and suggest that this mechanism is a major source of sequence variability among retrotransposed genetic elements.

DNA Replication↗

Biomolecular interaction analysis of IFN gamma-induced signaling events in whole-cell lysates: prevalence of latent STAT1 in high-molecular weight complexes.

The basic framework for the JAK/STAT pathway is well documented. Recruitment of latent cytoplasmic STAT transcription factors to tyrosine phosphorylated docking sites on cytokine receptors and their JAK-mediated phosphorylation instigates their translocation to the nucleus and their ability to bind DNA. The biochemical processes underlying recruitment and activation of this pathway have commonly been studied in reconstituted in vitro systems using previously defined recombinant signaling components. We have dissected the Interferon gamma (IFN gamma) signal transduction pathway in crude extracts from wild-type and STAT1-negative mutant cell lines by real-time BIAcore analysis, size-exclusion (SE) chromatography and immuno-detection. The data indicate that in detergent-free cell extracts: (1) the phospho-tyrosine (Y440P)-containing peptide motif of the IFN gamma-receptor alpha-chain interacts directly with STAT1, or STAT1 complexes, and no other protein; (2) non-activated STAT1 is present in a higher molecular weight complex(es) and, at least for IFN gamma-primed cells, is available for recruitment to the activated IFN gamma-receptor from only a subset of such complexes; (3) activated STAT1 is released from the receptor as a monomer.

Amino Acid Sequence↗

[Evaluation of fertility after surgery for varicocele in boys and adolescents].

Comparative estimation of potential fertility in 66 adolescents with varicocele shows: 1. Improvement of semen parameters in adolescents with over 20 x 10(6) spermatozoa in 1 cc. before operation and preserved spermatogenesis. 2. Increase of ipsilateral testicular volume in 86.4% of boys. 3. Apart from Ivanisevisch technique all applied surgical procedures demonstrate comparatively good results.

Adolescent↗

[The immunological and morphological aspects of chronic hepatitis caused by HBV].

The authors present in the study actual knowledge of the pathogenesis of the chronic viral hepatitis type B. Dividing of the disease into stages with description immunologic reactions connected with morphological features of the liver is used. Three stages of the disease have been reported: replication, elimination and integration of HBV in the liver. It present the results of immunohistological analysis of the incidence of the virus antigen in the tissue in the particular stages of the disease. Next it explains the mechanisms of immunological reaction leading to the incidence of particular forms of the inflammation activity and types of necrosis that occur in the chronic viral hepatitis type B.

Antigens, Viral↗

Glycemia-lowering effect of cobalt chloride in the diabetic rat: increased GLUT1 mRNA expression.

We have recently shown that expression of the GLUT1 glucose transporter isoform is augmented in cells exposed to cobalt chloride [Co(II)], an agent that stimulates the expression of hypoxia-responsive genes (Behrooz, A., Ismail-Beigi, F., 1997. J. Biol. Chem. 272, 5555-5562.). Here, we examine the effect of Co(II) on glycemia and tissue GLUT1 mRNA content of normal and diabetic rats. The addition of 2 mM Co(II) in the drinking water reduced the glycemia of streptozotocin-induced diabetic rats by day 3 from 32.3 +/- 2.1 to 21.0 +/- 1.9 mM (non-fasting). Co(II) resulted in no change in serum insulin levels of normal or diabetic rats. Treatment with 4 mM Co(II) was more effective than 2 mM Co(II) in reducing the glycemia of diabetic rats, while 6 mM Co(II) was associated with severe toxicity. GLUT1 mRNA content increased significantly in ventricular myocardium, renal cortex, skeletal muscle, cerebrum and liver of normal and diabetic rats treated with 2 mM cobalt chloride (ranging from 1.3- to 2.9-fold in the different tissues). It is concluded that: (1) treatment with Co(II) decreases the glycemia of diabetic rats, and (2) the glycemia-lowering effect of Co(II) is associated with, and may be mediated by, enhanced expression of GLUT1 mRNA.

Animals↗

Anomalous Dispersion with Edges in the Soft X-ray Region: First Results of Diffraction from Single Crystals of Trypsin Near the K-Absorption Edge of Sulfur.

Anomalous dispersion of X-ray diffraction at wavelengths near the X-ray K-absorption edge of sulfur at wavelengths around 5 A has been applied to single crystals of trypsin obtained from an ammonium sulfate solution. The multiwavelength anomalous-dispersion method based on 775 unique reflections (+183 Bijvoet mates) measured at three wavelengths near the K-absorption edge of sulfur in trypsin (two methionines and disulfide bridges of six cystines) reproduces the known features of the trypsin structure of a resolution of 4 A. It appears that there is anisotropic anomalous scattering from the disulfide bridges of cystine. The multiwavelength anomalous solvent contrast shows up at wavelengths near the K-absorption edge of the sulfate ions, which is shifted by 10 eV to higher energies with respect to that of sulfur in trypsin. The influence of the complex contrast of trypsin in 2.5 M ammonium sulfate on the dispersion of a low-order reflection is analyzed. The measurement of anomalous dispersion of X-ray diffraction at long wavelengths beyond 5 A requires a special diffractometer, the features of which are presented. An outstanding one is a detector system consisting of four multiwire proportional counters. Its efficiency is compared with that of imaging plates. The influence of radiation damage with soft X-ray diffraction from single crystals of trypsin is presented and possible remedies are discussed.

Journal Article↗

Hemostasis activation in patients undergoing brain tumor surgery.

Patients undergoing brain tumor surgery are at high risk for the occurrence of a thromboembolic event. To identify a laboratory marker suitable for risk estimation the authors studied the perioperative time pattern of routine coagulation parameters and the specific hemostasis activation marker D-dimer in 28 consecutive patients at high risk (11 patients with glioma and eight patients with meningioma) and low risk ( 9 patients with metastases) for thromboembolism, as previously reported. As is typical during major surgery, most of the routine parameters declined, probably because of hemodilution, and recovered postoperatively to values higher than baseline, probably because of an acute-phase reaction. On Days 2 and 7 after surgery no difference in the routine parameters was recorded between patients at high (meningioma and glioma) and low risk (metastases). The level of D-dimer was elevated at baseline in patients with metastases, indicating a hemostatic hyperactivity that is usual in cancer patients. During surgery a marked increase in D-dimer levels occurred in patients with meningioma and glioma (pre- and postoperative median 90/2000 and 100/1020 ng/ml, respectively), but the increase was less pronounced in patients with metastases (320/660 ng/ml). Postoperatively, D-dimer declined in patients with metastases to lower levels than preoperatively (Day 7, 270 ng/ml); in patients with meningioma or glioma, however, D-dimer levels remained elevated until Day 7 (450 and 200 ng/ml). These results indicate that levels of D-dimer correlate with the reported high risk for thromboembolism in patients with meningioma and glioma, and D-dimer should be evaluated for its use in estimating individual risk and the efficiency of its use in the control of prophylactic treatment.

Journal Article↗

DNA on the move.

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Animals↗

Many human L1 elements are capable of retrotransposition.

Using a selective screening strategy to enrich for active L1 elements, we isolated 13 full-length elements from a human genomic library. We tested these and two previously-isolated L1s (L1.3 and L1.4) for reverse transcriptase (RT) activity and the ability to retrotranspose in HeLa cells. Of the 13 newly-isolated L1s, eight had RT activity and three were able to retrotranspose. L1.3 and L1.4 possessed RT activity and retrotransposed at remarkably high frequencies. These studies bring the number of characterized active human L1 elements to seven. Based on these and other data, we estimate that 30-60 active L1 elements reside in the average diploid genome.

Animals↗

Morphometric study of the equine navicular bone: comparisons between fore and rear limbs.

Navicular bones collected from the four limbs of 95 sound horses were studied. The anatomic bases have been laid down about morphometry of the navicular bones and their variations according to limbs, after corrections have been made for morphologic type, gender, weight, size and age. All the dimensions of the navicular bone (except for the thickness) were larger in the fore limb. This phenomenon probably reflects an attempt to compensate for the greater forces exerted upon the fore limbs during exercise and at rest. Navicular bones collected from the four limbs of 61 sound horses were studied and the anatomic bases were described for histomorphometry of the fore and rear navicular bones. Fore navicular bones possess less cortical bone at the level of the articular surface, as well as at the level of the flexor surface and proximal border, but larger amounts of cancellous bone. Articular and flexor surface cortical bone show a larger porosity in the fore navicular bones and a larger amount of mineralized cartilage. The mineralized portion for distal impar- and collateral sesamoidean ligaments are also larger for the fore navicular bones. Two distinct zones are observed for the flexor surface cortex that have never been reported in the literature before: an external zone, which is mainly composed of poorly remodelled lamellar bone, arranged in a disto-proximal oblique direction, and an internal zone, which is mainly composed of secondary bone, with a latero-medial direction of Haversian canals. Bone architecture is discussed with regard to the mechanic load, encountered by the bone during locomotion.

Animals↗

Radiographical assessment of interphalangeal rotation in the evaluation of equine digital conformation.

This study is a part of a work to design a radiographical method to objectively define the conformation of an equine digit and to assess the individual appropriate trimming of a horse. Various angles were measured directly from the phalangeal bones. The authors observed that the bone relief of the sesamoid ligament insertions on the proximal phalanx was an essential landmark to determine the phalangeal alignment. The same angles were measured from specific radiographs and made it possible to quantify the rotation imposed to the proximal phalanx. The authors also noticed that the phalangeal rotation had little influence on the radiographic image of articular asymmetry.

Animals↗