MACS: automatic counting of objects based on shape recognition.
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Biology↗
Biomedical subjects
D Thomas
Publications and source records attributed to D Thomas.
Molecular characterization of two high affinity sulfate transporters in Saccharomyces cerevisiae.
Strains resistant to the toxic analogues of sulfate, selenate and chromate have been isolated. Their genetic analysis allowed us to identify four genes. One, called MET28, encodes a transcriptional factor. The three other genes, called SUL1, SUL2 and SUL3, encode proteins involved in sulfate transport. The sequence of Sul1p and Sul2p indicate that they are integral membrane proteins exhibiting, respectively, 11 and 10 transmembrane domains. Moreover, Sul1p and Sul2p share a high degree of similarity. Sulfate transport kinetic studies made with parental and mutant strains show that, as expected from genetic results, Saccharomyces cerevisiae has two high affinity sulfate transport systems. Sul3p has been shown to be involved in the transcriptional regulation of the SUL2 gene.
Amino Acid Sequence↗
Prognostic value of plasma endothelin-1 in patients with chronic heart failure.
AIMS: Endothelin-1 is a potent vasoconstrictive and multifunctional peptide. Elevated concentrations have been reported in congestive heart failure. We hypothesized that the level of endothelin-1 in plasma is a prognostic marker in congestive heart failure. METHODS AND RESULTS: Plasma levels of endothelin-1 were measured by radioimmunoassay in 120 congestive heart failure patients with ischaemic or non-ischaemic cardiomyopathy (mean ejection fraction 28 +/- 11%, in New York Heart Association (NYHA) functional class I:21, class II 35, class III: 61, class IV: 3). During a median follow-up of 361 +/- 338 days, 14 cardiac deaths occurred. In the univariate Cox model, endothelin-1 was the most powerful prognostic marker among the variables tested (P = 0.0001). A multivariate model, including plasma atrial natriuretic peptide and noradrenaline, NYHA class, age, and echocardiographic left ventricular end-diastolic diameter index was highly predictive of mortality (P = 0.00008), but only endothelin-1 remained significantly associated with outcome (P = 0.02). Patients with plasma endothelin-1 > or = 5 pg. ml-1 had a higher mortality rate than those with endothelin-1 < 5 pg. ml-1 (21% vs 4%, P = 0.001). CONCLUSION: Our results suggest that elevated endothelin-1 plasma levels are associated with a poor prognosis and routine plasma endothelin-1 determination provides important prognostic information in mild to moderate heart failure.
Atrial Natriuretic Factor↗
Intrathecal morphine for caesarean section: an assessment of pain relief, satisfaction and side-effects.
In a prospective, randomised, double-blind study of 60 patients who had an elective Caesarean section under spinal anaesthesia we compared 0.1 mg intrathecal morphine with intrathecal saline placebo. All patients received morphine intravenously by patient-controlled analgesia after the operation. Pain, satisfaction and side-effects were assessed at 4 and 24 h after the operation. Pain measured by a 100-mm visual analogue scale was less in the intrathecal morphine group at both times (p < 0.05) and morphine consumption was lower (p < 0.01). At 4 h the intrathecal morphine group had more pruritus (p < 0.001) but there was no difference in satisfaction. At 24 h there was no significant difference in side-effects, but overall satisfaction measured by visual analogue scale was better in the intrathecal morphine group (p < 0.01). Intrathecal morphine improves pain relief and patient satisfaction after Caesarean section.
Adult↗
Hemodynamic and neurohormonal effects of flosequinan in patients with heart failure.
In a double-blind, placebo-controlled study, the central and peripheral hemodynamic effects of 100 mg oral flosequinan and the impact of this drug on neurohormonal activation were noninvasively evaluated in 18 patients with congestive heart failure, after the first administration and after 10 days of treatment. No significant hemodynamic and neurohormonal changes were observed after acute administration. After 10 days, flosequinan produced central and peripheral hemodynamic improvement characterized by an increase in left ventricular circumferential fiber shortening velocity (+12%), a decrease in total systemic resistance (-36%), and an increase in leg blood flow (+37%). No significant changes were observed in heart rate and arterial pressure in patients receiving flosequinan, though a slight increase in heart rate (+17%) was recorded. Despite these favorable hemodynamic effects, flosequinan significantly increased plasma norepinephrine (+38%) and plasma renin activity (+13%) after 10 days of treatment. Thus, the beneficial central and peripheral hemodynamic effects of flosequinan are accompanied by activation of the sympathetic and reninangiotensin systems. This might be related to the unfavorable effects of the drug on survival in patients with heart failure.
Adult↗
Development of the Nimbus/Pittsburgh axial flow left ventricular assist system.
Nimbus, Inc. and the University of Pittsburgh's School of Medicine have been collaborators developing rotary blood pump technology since 1992. Currently, a major focus is on an implantable left ventricular assist system (LVAS) that utilizes an electric powered axial flow blood pump. In addition to the blood pump, a major development item is the electronic controller and the control algorithm for modulating the pump speed in response to varying physiologic demands. Methods being used in developing the axial flow LVAS include the use of computational fluid dynamic modeling of the interior flow field of the pump, flow visualization of the flow field using laser based imaging, and computer simulation of blood pump-physiological interactions as well as an extensive in vivo test program. Results to date include successful in vivo tests of blood pumps with nonlubricated bearings and demonstrations of auto speed control using electrical current as the observable parameter.
Algorithms↗
Temperate Myxococcus xanthus phage Mx8 encodes a DNA adenine methylase, Mox.
Temperate bacteriophage Mx8 of Myxococcus xanthus encapsidates terminally repetitious DNA, packaged as circular permutations of its 49-kbp genome. During both lytic and lysogenic development, Mx8 expresses a nonessential DNA methylase, Mox, which modifies adenine residues in occurrences of XhoI and PstI recognition sites, CTCGAG and CTGCAG, respectively, on both phage DNA and the host chromosome. The mox gene is necessary for methylase activity in vivo, because an amber mutation in the mox gene abolishes activity. The mox gene is the only phage gene required for methylase activity in vivo, because ectopic expression of mox as part of the M. xanthus mglBA operon results in partial methylation of the host chromosome. The predicted amino acid sequence of Mox is related most closely to that of the methylase involved in the cell cycle control of Caulobacter crescentus. We speculate that Mox acts to protect Mx8 phage DNA against restriction upon infection of a subset of natural M. xanthus hosts. One natural isolate of M. xanthus, the lysogenic source of related phage Mx81, produces a restriction endonuclease with the cleavage specificity of endonuclease BstBI.
Amino Acid Sequence↗
Met31p and Met32p, two related zinc finger proteins, are involved in transcriptional regulation of yeast sulfur amino acid metabolism.
Sulfur amino acid metabolism in Saccharomyces cerevisiae is regulated by the level of intracellular S-adenosylmethionine (AdoMet). Two cis-acting elements have been previously identified within the 5' upstream regions of the structural genes of the sulfur network. The first contains the CACGTG motif and is the target of the transcription activation complex Cbflp-Met4p-Met28p. We report here the identification of two new factors, Met31p and Met32p, that recognize the second cis-acting element. Met31p was isolated through the use of the one-hybrid method, while Met32p was identified during the analysis of the yeast methionine transport system. Met31p and Met32p are highly related zinc finger-containing proteins. Both LexA-Met31p and LexA-Met32p fusion proteins activate the transcription of a LexAop-containing promoter in a Met4p-dependent manner. Northern blot analyses of cells that do not express either Met31p and/or Met32p suggest that the function of the two proteins during the transcriptional regulation of the sulfur network varies from one gene to the other. While the expression of both the MET3 and MET14 genes was shown to strictly depend upon the presence of either Met31p or Met32p, the transcription of the MET25 gene is constitutive in cells lacking both Met31p and Met32p. These results therefore emphasise the diversity of the mechanisms allowing regulation of the expression of the methionine biosynthetic genes.
Amino Acid Sequence↗
Metabolism of sulfur amino acids in Saccharomyces cerevisiae.
Sulfur amino acid biosynthesis in Saccharomyces cerevisiae involves a large number of enzymes required for the de novo biosynthesis of methionine and cysteine and the recycling of organic sulfur metabolites. This review summarizes the details of these processes and analyzes the molecular data which have been acquired in this metabolic area. Sulfur biochemistry appears not to be unique through terrestrial life, and S. cerevisiae is one of the species of sulfate-assimilatory organisms possessing a larger set of enzymes for sulfur metabolism. The review also deals with several enzyme deficiencies that lead to a nutritional requirement for organic sulfur, although they do not correspond to defects within the biosynthetic pathway. In S. cerevisiae, the sulfur amino acid biosynthetic pathway is tightly controlled: in response to an increase in the amount of intracellular S-adenosylmethionine (AdoMet), transcription of the coregulated genes is turned off. The second part of the review is devoted to the molecular mechanisms underlying this regulation. The coordinated response to AdoMet requires two cis-acting promoter elements. One centers on the sequence TCACGTG, which also constitutes a component of all S. cerevisiae centromeres. Situated upstream of the sulfur genes, this element is the binding site of a transcription activation complex consisting of a basic helix-loop-helix factor, Cbf1p, and two basic leucine zipper factors, Met4p and Met28p. Molecular studies have unraveled the specific functions for each subunit of the Cbf1p-Met4p-Met28p complex as well as the modalities of its assembly on the DNA. The Cbf1p-Met4p-Met28p complex contains only one transcription activation module, the Met4p subunit. Detailed mutational analysis of Met4p has elucidated its functional organization. In addition to its activation and bZIP domains, Met4p contains two regulatory domains, called the inhibitory region and the auxiliary domain. When the level of intracellular AdoMet increases, the transcription activation function of Met4 is prevented by Met30p, which binds to the Met4 inhibitory region. In addition to the Cbf1p-Met4p-Met28p complex, transcriptional regulation involves two zinc finger-containing proteins, Met31p and Met32p. The AdoMet-mediated control of the sulfur amino acid pathway illustrates the molecular strategies used by eucaryotic cells to couple gene expression to metabolic changes.
Amino Acids, Sulfur↗
Evaluation of a novel endoluminal brush method for in situ diagnosis of catheter related sepsis.
AIMS: To determine the accuracy of a novel endoluminal brush method for the diagnosis of catheter related sepsis (CRS), which is performed in situ and hence does not require line sacrifice. METHODS: 230 central venous catheters in 216 patients were examined prospectively for evidence of CRS or colonisation using an endoluminal brush method in conjunction with peripheral blood cultures. The results were compared with those obtained using methods that require line sacrifice: extraluminal sampling (Maki roll) or endoluminal sampling (modified Cleri flush) of microorganisms. RESULTS: Only 16% of 128 patients suspected clinically of having line associated infection were confirmed as having CRS. In addition, 2 of 102 patients not suspected of having line associated infection had CRS. Line colonisation was apparent in approximately twice as many catheters using the Maki roll criteria (92%) compared with either the endoluminal brush (43%) or Cleri flush (43%). Furthermore, colonised catheters sampled using the Maki roll technique yielded mixed growth twice as often as when examined by endoluminal methods (17 and 8 cases, respectively). It was rare to detect either only endoluminal (4 of 22 episodes) or extraluminal (1 of 22 episodes) microorganisms in cases of CRS. In contrast, catheters defined as being colonised most frequently (59% of episodes) yielded only significant extraluminal growth. Only one case of CRS (5%) would have been "missed" if lines yielding a negative result from endoluminal brush sampling had been left in situ. Conversely, four episodes of CRS (18%) would not have been diagnosed by relying on extraluminal sampling alone. CONCLUSIONS: Diagnosis of CRS by the endoluminal brush method can be achieved without line sacrifice and is more sensitive (95%) and specific (84%) than extraluminal sampling of the catheter tip by the Maki roll technique (82% and 66%, respectively).
Adolescent↗
Neuromuscular blockade with acute respiratory failure in a patient receiving cibenzoline.
Cibenzoline is a class Ic antiarrhythmic agent that can be used to treat supraventricular arrhythmias. A case is reported of cibenzoline overdose in a patient with impaired renal function, leading not only to the usual cardiac and metabolic symptoms (bradycardia and hypoglycaemia), but also to a myastheniform syndrome with acute respiratory failure. Neuromuscular blockade was demonstrated by repetitive supramaximal stimulation of the median nerve, and diaphragmatic involvement was evidenced by applying the same protocol to the phrenic nerve. Muscle strength recovered as serum cibenzoline levels decreased, allowing the patient to be weaned from the ventilator. This observation suggests that cibenzoline, like other antiarrhythmic agents, can be responsible for neuromuscular blockade, and should therefore be used with caution in patients with neuromuscular and respiratory diseases or with impaired renal function.
Acute Disease↗
Nuclear export signal of IkappaBalpha interferes with the Rev-dependent posttranscriptional regulation of human immunodeficiency virus type I.
De novo synthesized IkappaBalpha accumulates transiently in the nucleus where it inhibits NF-kappaB-dependent transcription and reduces nuclear NF-kappaB content. A sequence present in the C-terminal domain of IkappaBalpha and homologous to the HIV-1 Rev nuclear export signal (NES) has been recently defined as a functional NES conferring on IkappaBalpha the ability to export IkappaBalpha/NF-kappaB complexes. Rev utilises its RNA-binding activity and NES sequence to promote specifically the transport of unspliced and monospliced viral RNAs to the cytoplasm. The object of this work was to determine if nuclear IkappaBalpha could interfere with Rev-dependent transport of viral RNA from the nucleus to the cytoplasm. We report that accumulation of IkappaBalpha in the cell nucleus blocks viral replication. This effect could be dissociated from the capacity of IkappaBalpha to inhibit NF-kappaB-DNA-binding activity and required a functional IkappaBalpha NES motif. Indeed, mutation of the NES abrogated the capacity of IkappaBalpha to inhibit Rev-dependent mechanisms involved in the replication of either wild-type or NF-kappaB-mutated HIV-1 molecular clones. Nuclear accumulation of a reporter protein tagged with a nuclear localization signal (NLS) and fused to the IkappaBalpha NES motif (NLS-PK-NES) was sufficient to inhibit HIV-1 replication at a post-transcriptional level by specifically blocking the expression of a Rev-dependent gene. Furthermore, in cells pulsed with TNF, a treatment which favors nuclear accumulation of newly synthesized IkappaBalpha, NLS-PK-NES expression promoted sustained accumulation of nuclear NF-kappaB lacking DNA-binding activity. This NES-mediated accumulation of inactive nuclear NF-kappaB is likely the consequence of interference in the IkappaBalpha-mediated export of NF-kappaB. These findings indicate that IkappaBalpha and Rev compete for the same nuclear export pathway and suggest that nuclear accumulation of IkappaBalpha, which would occur during normal physiological cell activation process, may interfere with the Rev-NES-mediated export pathway of viral RNAs, thus inhibiting HIV-1 replication.
Animals↗
Nuclear localization of I kappa B alpha promotes active transport of NF-kappa B from the nucleus to the cytoplasm.
I kappa B alpha tightly regulates the transcriptional activity of NF-kappa B by retaining it in the cytoplasm in an inactive form. In the present work, we report that I kappa B alpha, when expressed in the nuclear compartment, not only abrogates NF-kappa B/DNA interactions and NF-kappa B-dependent transcription, but also transports NF-kappa B back to the cytoplasm. This function of I kappa B alpha is insured by a nuclear export sequence located in the C-terminal domain of I kappa B alpha and homologous to the previously described export signal found in HIV-1 Rev protein as well as in PKI (the inhibitor of the catalytic subunit of protein kinase A). Thus, inhibition of NF-kappa B/DNA binding and the consecutive efficient nuclear export of the transcription factor of I kappa B alpha could represent an important mechanism for the control of the expression of NF-kappa B-dependent genes.
Amino Acid Sequence↗
Blood anion gaps and venoarterial carbon dioxide gradients as risk factors in long-term extracorporeal support.
Increases in the blood anion gap (AG) and venoarterial carbon dioxide gradients [p(V-A)CO2] may indicate changes in intracellular acid concentration not demonstrated by blood gas measurements. This prospective study examines these two physiologic markers to determine their relationship to extracorporeal membrane oxygenation (ECMO) survival and duration in 100 patients. Serum electrolytes were drawn every 6 hours and the AG calculated. Simultaneous arterial blood gases and venous blood gases were drawn every 4 hours and the p(V-A)CO2 calculated. Cumulative averages were then calculated from all the AG and p(V-A)CO2 values during each ECMO treatment. The average AG was 11 mEq/L. The average p(V-A)CO2 was 9 mm of mercury (mmHg). Patients with an AG of 11 mEq/L or less had a 12% mortality and those with a higher AG had a 43% mortality (p = 0.0005). Patients with a p(V-A)CO2 of less than 9 mmHg had a 13% mortality and those with a 9 mmHg or higher gradient had a 35% mortality (p = 0.0126). Patients with both a low AG and a low p(V-A)CO2 had a 7% mortality and survivors were on ECMO 100 (+/-37) hours. Patients with both a high AG and a high p(V-A)CO2 had a 56% mortality and survivors were on ECMO 190 (+/-105) hours. Both mortality and survivors' ECMO time increase as one or both risk factors increase. Patients with increases in both risk factors have a mortality rate 8 times greater and survivors remain on ECMO almost twice as long as those without increased risk factors. Patients may benefit from a perfusion strategy that seeks to minimize the AG and p(V-A)CO2.
Acid-Base Equilibrium↗
Radiologic-pathologic correlation polymicrogyria.
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Adult↗
Choristomas of the seventh and eighth cranial nerves.
Choristomas, masses of normal tissues in aberrant locations, contain smooth muscle fibers and fibrous tissues. We describe the MR imaging features of two choristomas located in the internal auditory canals and arising from the facial and vestibulocochlear nerves. Both lesions enhanced with contrast material. In one case, enhancement was seen in the geniculate ganglion and greater superficial petrosal nerve. In the other, a medial component enhanced less than the lateral component did.
Adult↗
Immunohistochemical study of secretogranin II in 62 neuroendocrine tumours of the digestive tract and of the pancreas in comparison with other granins.
An immunohistochemical study on 62 cases of gastrointestinal and pancreatic neuroendocrine tumours was performed in order to test the interest and specificity of a new anti-human secretogranin II antibody and compared to the other granin markers (chromogranin A and chromogranin B). Specific immunoglobulins were purified by affinity chromatography from an antiserum raised against a recombinant secretogranin II. Gastric tumours did not express secretogranin II, and ileal and appendiceal tumours only rarely expressed it (1/10 and 1/7 respectively), unlike the other classic neuroendocrine members of the granin family. In duodenal and pancreatic tumours, secretogranin II was detected when the other granins were also expressed. On the other hand, all rectal tumours expressed secretogranin II (7/7), frequently in the absence of chromogranin A. Though the granins expressed in tumoral tissue and in adjoining non tumoral tissue are mostly related, strong secretogranin II positivity occurred in 4 tumours while mucosa was secretogranin II negative. These observations highlight the interest for associating another antigranin such as secretogranin II to the classical markers of neuroendocrine tumours.
Adolescent↗
[Passive smoking and cardiovascular diseases].
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Cardiovascular Diseases↗