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PubMed2000

Retrograde perfusion and true reverse brain blood flow in humans.

OBJECTIVE: Reversal of brain blood flow is necessary for retrograde cerebral perfusion (RCP) to have any metabolic benefit, but RCP is commonly used with little clinical evidence of the true incidence of reverse brain blood flow and impact. S-100B is exclusive to the brain and spinal cord and released during hypothermic circulatory arrest (HCA). True reverse brain blood flow (tRBBF) during RCP may be determined by demonstrating an excess of S-100B in the effluent blood from the common carotid artery compared to blood entering the brain. METHODS: Simultaneous blood samples were drawn from the jugular bulb and left common carotid artery during RCP at 5 min intervals in ten patients undergoing aortic surgery, utilizing HCA and subjected to blood gas, glucose and S-100B quantification. RCP was instituted at maximum pressure of 25 mmHg. Trans-cranial Doppler (TCD) continuously monitored the middle cerebral artery velocity (MCAV). RESULTS: The mean HCA and RCP durations were 31 min (20-50 min). Reversal of MCAV was demonstrated in only 6/10 cases (mean, 6 cm/s). Veno-arterial (V-A) extraction of oxygen and glucose occurred in all cases (P<0.001), with the mean effluent pO(2) falling to 14 mmHg. V-A S-100 gradients greater than 5% were demonstrated in 8/10 cases and correlated with higher oxygen extraction (P<0.01). In patients with and without MCAV reversal, the S-100 gradients were 1. 7 and 0.3 micromol/l, respectively (P<0.01). CONCLUSIONS: tRBBF occurred in nearly all patients. MCAV reversal appears to be a specific but insensitive guide to reverse perfusion. The de-saturation of effluent blood is not a reliable guide to true brain perfusion, and despite RCP, the brain remains ischaemic.

Biomarkers↗
PubMedDate not supplied

Effects of myocardial revascularization on regional thallium-201 uptake and systolic function in regions with reverse redistribution on tomographic thallium-201 imaging at rest in patients with chronic coronary artery disease.

OBJECTIVES: There is growing evidence that myocardial segments with reverse redistribution are viable in patients with chronic coronary artery disease. The aim of this study was to assess the effects of myocardial revascularization on systolic function and thallium-201 uptake in such segments. METHODS: Rest-redistribution thallium-201 tomography before and after myocardial revascularization was performed in 47 patients with chronic coronary artery disease. Regional function was evaluated by two-dimensional echocardiography before and after revascularization according to a 3-point scale (1 = normal, 2 = hypokinetic, 3 = a/dyskinetic). Improvement of dysfunctional segments was defined when systolic function score decreased > or =1 after revascularization. Reverse redistribution was defined as >8% decrease in relative thallium-201 uptake between rest and redistribution images. RESULTS: Reverse redistribution was found in 27 (57%) of 47 patients, corresponding to 60 (11%) of 564 myocardial segments. Of such segments, 24 (40%) had normal systolic function, 19 (32%) were hypokinetic, and 17 (28%) were a/dyskinetic. Thirty-six segments underwent myocardial revascularization, and reverse redistribution was no longer present in 86% of them subsequent to the procedure. Of 26 dyssynergic segments with reverse redistribution subjected to revascularization, 18 (69%) improved at follow-up. CONCLUSIONS: The findings of the present study indicate that reverse redistribution is a reversible phenomenon and is often associated with improvement of systolic function following revascularization in patients with chronic coronary artery disease.

Aged↗
PubMed2000

Refolding of cytochrome c using reversed micelles.

A novel protein refolding method using reversed micelles has been developed, which could replace the conventional dilution method using a buffer solution. The novel refolding method enables efficient refolding at a high protein concentration. In the present study, denatured bovine heart cytochrome c was directly solubilized in AOT reversed micelles using the solid-liquid extraction technique. Results reveal that addition of urea in small amounts facilitates solubilization of denatured protein into the reversed micellar phase. Reversed micelles containing a high concentration of denatured cytochrome c could be easily prepared by the novel solubilization method. The nanostructural environment formed by the surfactant molecules in organic media is considered to promote the renaturation of denatured proteins because the protein molecules are isolated from each other through the solubilization step. Although the recovery of entrapping proteins from the reversed micellar phase was known to be difficult in a conventional reversed micellar extraction operation, the addition of alcohol to the recovery phase improved the efficiency of back extraction. Therefore, we succeeded in recovering renatured cytochrome c from the reversed micelles. We demonstrated that the novel protein refolding method is very useful for the renaturation of denatured proteins.

Journal Article↗
PubMed1995

Water requirements in monomer folding and dimerization of triosephosphate isomerase in reverse micelles. Intrinsic fluorescence of conformers related to reactivation.

The possibility of using reverse micelles to stabilize monomers prior to formation of dimeric triosephosphate isomerase (TPI) from rabbit muscle was studied. TPI denatured with guanidine hydrochloride undergoes reactivation in reverse micelles formed with n-octane, hexanol, cetyltrimethylammonium bromide, and water. Reactivation of around 80% is observed at TPI concentrations of about 2 micrograms/mL of reverse micelles and water concentrations above 4.0%. With 3.0% water, reactivation is about 10%. If denatured TPI is incubated for a few seconds in reverse micelles with 5.0% water (or higher) followed by incubation in 3.0% water, reactivation is between 35% and 50%. That is, a brief exposure of denatured TPI to reverse micelles with a relatively high water concentration yielded a significant amount of structures competent for formation of catalytically active dimers. As evidenced by kinetic data, these structures correspond to monomers of TPI [Garza-Ramos, G. Tuena de Gómez-Puyou, M., Gómez-Puyou, A., & Gracy R. W. (1992) Eur. J. Biochem. 208, 389-395]. After a 5-2.0% water transition, competent monomers were stabilized for at least 30 min; a subsequent rise in water concentration led to dimerization and appearance of activity. By changes in the amount of water, it was possible to determine in reverse micelles the amount of water required for monomer folding and dimerization; i.e., less water was required in the dimerization step. Experiments with a model system, trypsin and the soybean inhibitor, showed that, in reverse micelles with 2.0% water, protein-protein interactions readily take place.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Fidelity of HIV-1 reverse transcriptase copying RNA in vitro.

The genomic hypervariation of human immunodeficiency virus 1 (HIV-1) could result from misincorporations by the viral reverse transcriptase. We developed an assay for reverse transcriptase fidelity during RNA-dependent as well as DNA-dependent DNA polymerization in vitro. A lacZ alpha RNA fragment transcribed by T3 RNA polymerase was used to mimic first-strand reverse transcription. The corresponding DNA template was used to examine errors by reverse transcriptase during second-strand DNA synthesis. With both templates, the mutations introduced by reverse transcriptase were identified by their mutant phenotypes in an M13 lacZ alpha-complementation assay. We found that the reverse transcriptase from human immunodeficiency virus 1 (HIV-1 RT) was less accurate than the reverse transcriptase from Moloney murine leukemia virus (MLV RT) or the Klenow fragment of Escherichia coli DNA polymerase I (Pol I) on either RNA or DNA templates. The frequency of misincorporation by HIV-1 RT was 1 in 6900 nucleotides polymerized on the RNA template and 1 in 5900 on the DNA template. The error rates of MLV RT and Pol I on the RNA template were less than 1 in 28,000 and 37,000, respectively. The most frequent mutations produced by HIV-1 RT copying the RNA template were C----T transitions and G----T transversions resulting from misincorporation of dAMP.

Animals↗
PubMed1988

Effect of pulsed and reversing electric fields on the orientation of linear and supercoiled DNA molecules in agarose gels.

When linear or supercoiled DNA molecules are imbedded in agarose gels and subjected to electric fields, they become oriented in the gel matrix and give rise to an electric birefringence signal. The sign of the birefringence is negative, indicating that the DNA molecules are oriented parallel to the electric field lines. If the DNA molecules are larger than about 1.5 kilobase pairs, a delay is observed before the birefringence signal appears. This time lag, which is roughly independent of DNA molecular weight, decreases with increasing electric field strength. The field-free decay of the birefringence is much slower for the DNA molecules imbedded in agarose gels than observed in free solution, indicating that orientation in the gel is accompanied by stretching. Both linear and supercoiled molecules become stretched, although the apparent change in conformation is much less pronounced for supercoiled molecules. When the electric field is rapidly reversed in polarity, very little change in the birefringence signal is observed for linear or supercoiled DNAs if the equilibrium orientation (i.e., birefringence) had been reached before field reversal. Apparently, completely stretched, oriented DNA molecules are able to reverse their direction of migration with little or no loss of orientation. If the steady-state birefringence had not been reached before the field reversal, complicated orientation patterns are observed after field reversal. Very large, partially stretched DNA molecules exhibit a rapid decrease in orientation at field reversal. The rate of decrease of the birefringence signal in the reversing field is faster than the field-free decay of the birefringence and is approximately equal to the rate of orientation in the field (after the lag period).(ABSTRACT TRUNCATED AT 250 WORDS)

Birefringence↗
PubMed2004

Reverse micellar aggregates: effect on ketone reduction. 2. Surfactant role.

Kinetics of the reduction of 3-chloroacetophenone (CAF) with sodium borohydride (NaBH(4)) were followed by UV-vis spectroscopy at 27.0 degrees C in different reverse micellar media, toluene/BHDC/water and toluene/AOT/water, and compared with results in an isooctane/AOT/water reverse micellar system. AOT is sodium 1,4-bis-2-ethylhexylsulfosuccinate, and BHDC is benzyl-n-hexadecyl dimethylammonium chloride. The kinetic profiles were investigated as a function of variables such as surfactant and NaBH(4) concentration and the amount of water dispersed in the reverse micelles, W(0) = [H(2)O]/[surfactant]. In all cases, the first-order rate constant, k(obs), increases with the concentration of surfactant as a consequence of incorporating the substrate into the interface of the reverse micelles where the reaction takes place. The reaction is faster at the cationic interface than at the anionic one probably because the negative ion BH(4)(-) is part of the cationic interface. The effect of the external solvent on the reaction shows that reduction is favored in the isooctane/AOT/water reverse micellar system than that with an aromatic solvent. This is probably due to BH(4)(-) being more in the water pool of the toluene/AOT/water reverse micellar system. The kinetic profile upon water addition depends largely on the type of interface. In the BHDC system, k(obs) increases with W(0) in the whole range studied while in AOT the kinetic profile has a maximum at W(0) approximately 5, probably reflecting the fact that BH(4)(-) is part of the cationic interface while, in the anionic one, there is a strong interaction between water and the polar headgroup of AOT below W(0) = 5 and, above that, BH(4)(-) is repelled from the interface once the water pool has formed. Application of a kinetic model based on the pseudophase formalism, which considers the distribution of the ketone between the continuous medium and the interface and assumes that reaction takes place only at the interface, has enabled us to estimate rate constants at the interface of the reverse micellar systems. At W(0) < 10, it was considered that NaBH(4) is wholly at the interface and, at W(0) >/= 10, where there are free water molecules, also the partitioning between the interface and the water pool was taken into account. The results were used to evaluate CAF and NaBH(4) distribution constants between the different pseudophases as well as the second-order reaction rate constant of the reduction reaction in the micellar interface.

Journal Article↗
PubMed2005

Dynamics of nanoscopic water: vibrational echo and infrared pump-probe studies of reverse micelles.

The dynamics of water in nanoscopic pools 1.7-4.0 nm in diameter in AOT reverse micelles were studied with ultrafast infrared spectrally resolved stimulated vibrational echo and pump-probe spectroscopies. The experiments were conducted on the OD hydroxyl stretch of low-concentration HOD in the H2O, providing a direct examination of the hydrogen-bond network dynamics. Pump-probe experiments show that the vibrational lifetime of the OD stretch mode increases as the size of the reverse micelle decreases. These experiments are also sensitive to hydrogen-bond dissociation and reformation dynamics, which are observed to change with reverse micelle size. Spectrally resolved vibrational echo data were obtained at several frequencies. The vibrational echo data are compared to data taken on bulk water and on a 6 M NaCl solution, which is used to examine the role of ionic strength on the water dynamics in reverse micelles. Two types of vibrational echo measurements are presented: the vibrational echo decays and the vibrational echo peak shifts. As the water nanopool size decreases, the vibrational echo decays become slower. Even the largest nanopool (4 nm, approximately 1000 water molecules) has dynamics that are substantially slower than bulk water. It is demonstrated that the slow dynamics in the reverse micelle water nanopools are a result of confinement rather than ionic strength. The data are fit using time-dependent diagrammatic perturbation theory to obtain the frequency-frequency correlation function (FFCF) for each reverse micelle. The results are compared to the FFCF of water and show that the largest differences are in the slowest time scale dynamics. In bulk water, the slowest time scale dynamics are caused by hydrogen-bond network equilibration, i.e., the making and breaking of hydrogen bonds. For the smallest nanopools, the longest time scale component of the water dynamics is approximately 10 times longer than the dynamics in bulk water. The vibrational echo data for the smallest reverse micelle displays a dependence on the detection wavelength, which may indicate that multiple ensembles of water molecules are being observed.

Deuterium↗
PubMed1999

Reversibility of heat-induced denaturation of the recombinant human megakaryocyte growth and development factor.

PURPOSE: The present study was performed to examine the effect of solution conditions on the reversibility of the thermal denaturation of megakaryocyte growth and development factor (rHuMGDF). METHODS: Changes in the far UV CD spectra of rHuMGDF with temperature were used to monitor the thermal denaturation of the protein, and the recovery of folded protein following a return to room temperature. The effect of protein concentration, scan rate, and buffer composition on thermal denaturation and on the reversibility were determined. Surface tension measurements were used to determine the effect of this unfolding reaction on the surface adsorption of the protein. Sedimentation velocity was used to assess recovery of native monomer and the size of soluble aggregates. In addition, monomeric protein remaining in solution after incubation at 37 degrees C for 2 weeks in either 10 mM imidazole of 10 mM phosphate was determined. RESULTS: In phosphate buffer the rHuMGDF irreversibly precipitates upon unfolding under all the conditions examined. In imidazole the unfolding is at least partially reversible, with no visible precipitate seen; the degree of reversibility increased by lowering both protein and salt concentrations, and the amount of time spent at elevated temperature. In order to compare thermal unfolding occuring with different degrees of reversibility, the melting temperature was defined as the temperature at which melting begins. The melting temperature itself is relatively independent of the buffer composition, or experimental conditions. At low protein concentrations the protein stabilizer sucrose had a marginal effect on the thermal transition of rHuMGDF, while at protein concentrations of about 2 mg/ml the inclusion of sucrose increased the apparent melting temperature by about 4 degrees C, to that seen at low protein concentrations, but had little effect on the reversibility of denaturation. Inclusion of 1 or 2 M urea did not affect the reaction. Surface tension measurements of rHuMGDF solutions showed little difference before and after melting, and in the presence or absence of sucrose. When unfolding is irreversible, the MGDF appears to form soluble aggregates of tetramers to 14-mers, while under reversible conditions native monomer is recovered. More monomeric MGDF remained in solution following storage for 2 weeks at 37 degrees C in imidazole than in phosphate, in both the presence and absence of sucrose. CONCLUSIONS: These results can be explained by assuming that thermal denaturation proceeds as a two-step reaction, the first step being the equilibrium between folded and unfolded states, while the second step is a slow irreversible aggregation. The different buffer systems affect the rate of the aggregation step, but not the intrinsic thermal stability nor the rate of the unfolding step.

Buffers↗
PubMed1996

Correlation between Banff classification, acute renal rejection scores and reversal of rejection.

The Banff classification of acute rejection is based on histologic grades and scores for borderline changes, glomerular, vascular, interstitial and tubular lesions. We reviewed 56 episodes of acute rejection occurring in 44 kidney allograft recipients (30 cadaveric and 14 living donor transplants), comparing Banff classification to degree of reversibility of rejection. Rejection reversal was defined as complete if serum creatinine returned < or = 25% of baseline, partial if creatinine was > 25% to < 75% of baseline, and irreversible if creatinine was > or = 75% of baseline or graft loss occurred. Eight biopsies were classified as borderline (SUM score 1.6 +/- 0.5), 14 grade I (SUM score 3.3 +/- 0.4), 19 grade II (SUM score 4.2 +/- 0.3), and 15 grade III (SUM score 8.5 +/- 0.4). SUM distinguished borderline and grade III rejections, but not grades I and II. Clinically, grade and SUM score correlated with rejection reversal. Complete reversal of rejection occurred in 93% of patients with grade I rejection, while 47% of patients with grade III had irreversible rejection. The mean SUM for complete reversal was 3.9 +/- 0.34 and was different from SUM of partial (6.0 +/- 0.86) and irreversible (8.5 +/- 0.93), P < 0.006. Meanwhile, vascular scores were similar for rejections with complete (0.9 +/- 0.2) or partial (1.0 +/- 0.4) reversal, but significantly higher in those with irreversible rejection (3.0 +/- 0.4, P < 0.000). Likewise, mean scores for tubulitis and interstitial inflammation were significantly higher for irreversible rejection. Resolution of rejection by steroids was correlated to low vascular score (steroid sensitive 0.65 +/- 0.25 vs. steroid resistant 1.42 +/- 0.18, P < 0.01), and low SUM score (steroid sensitive 3.7 +/- 0.5 vs. steroid resistant 5.22 +/- 0.43, P < 0.04). Neither scores for tubulitis nor interstitial cellular inflammation were predictive of steroid sensitivity. These data demonstrate that Banff scoring has clinical relevance in predicting rejection reversal and has implications to first-line therapy of rejection episodes.

Adolescent↗
PubMed1989

A theoretical study on the expression of enzymic activity in reverse micelles.

The present work deals with a theoretical model of catalysis by enzymes entrapped in reverse micelles. Three aspects of the enzyme-reverse-micelle system have been considered: structure, dynamics and enzyme distribution and catalysis in reverse micelles. A proposed structural model of reverse micelles [El Seoud (1984) in Reverse Micelles (Luisi, P. L. & Straub, B. E., eds.), p. 81, Plenum Press, New York] consists of three domains: surfactant apolar tails, bound water and free water. Dynamics are based on a dynamic equilibrium of association-dissociation that lead one to consider the dispersed polar phase as a pseudo-continuous phase [Luisi, Giomini, Pileni & Robinson (1988) Biochim. Biophys. Acta 947, 207-246]. Enzyme is distributed among the reverse-micelle domains and it expresses a catalytic constant for each one of them. The overall activity is calculated taking into account the volume in which enzyme is solubilized, and expressed as a function of the whole volume (V). The characteristic parameters of reverse micelles, omega 0 (= [H2O]/[surfactant]) and theta (= % water, v/v), were investigated as modulators of enzymic activity. Three basic patterns of modulation by omega 0 were found depending on which domain the enzyme expressed the highest catalytic constant. Combinations of those basic patterns lead to other modulation types that can be found experimentally, such as superactivation. Other combinations predict behaviour patterns not described to date, such as superinhibition. Dependence of catalytic activity on theta was only stated at omega 0 values around a critical value, which coincides with the appearance of free water.

Catalysis↗
PubMed1998

Clinical experience with the use of clotting factor concentrates in oral anticoagulation reversal.

We report the clinical experience of a large Haemophilia Centre and Haemostasis Unit in reversing oral anticoagulation (OAC) using clotting factor concentrates. This is a retrospective study extending over 2 years (January 1996-December 1997). Reversal was performed using a combination of factor IX and factor VII concentrates administered by intravenous infusion. in a dose varying between 12 i.u./kg and 50 i.u./kg. We identified 20 episodes of OAC reversal in 18 patients, with a prevalence of 10 reversal episodes/1000 OAC patients/year. The median age was 77 years old (range 53-92 years). Indications for OAC reversal were divided into major bleeds (muscle haematoma [9], haematuria [3], subarachnoid haemorrhage [1], oesophageal bleeding [1], haemoptysis [1], haemarthrosis [1]); minor bleeds (extensive bruising [9], epistaxis [3], oral cavity bleeding [1]); and emergency invasive investigation (2). Pre-reversal, the international normalized ration (INR) was greater than 6.0 in 15/18 patients. Post-infusion. there was an immediate reduction in the INR towards normal (mean 1.3; range 1.1-2.3). There were no thrombotic complications or other adverse effects. The median use of factor 9 A concentrate was 2300 units/patient (range 570-4195), at a cost of 645 Pounds/patient and for factor VII concentrate 2200 units/patient (range 815-3630), at a cost of 664 Pounds/patient. Clotting factor concentrates provide a safe, rapid and effective means for OAC reversal and although expensive it is the treatment of choice in the over anticoagulated, bleeding patient.

Aged↗
PubMed2002

Incisal and condylar paths during habitual mouth opening movement of children with anterior reverse bite in the primary dentition.

The purpose of this study was to evaluate whether the path of habitual mouth opening was influenced by anterior reverse bite malocclusion in children. Two groups of children with the primary dentition were chosen: (i) 10 children with anterior reverse bite (reverse bite group) and (ii) 10 with normal occlusion (normal occlusion group). Their habitual mouth opening movements were measured by an opto-electronic movement-analysing system with 6 d.f. at a sampling rate of 100 Hz. These movements were projected on the sagittal plane at the incisal and condylar points. To characterize the path, we used the angles between the path and the horizontal plane. In the initial stage of opening, the incisal path of the reverse bite group was displaced more posteriorly from the intercuspal position than that of the normal occlusion group. However, as opening continued, the direction of the path of the reverse bite group was more anterior than those of the normal occlusion group. During the entire opening movement, the condylar path of the reverse bite group was flatter than those of the normal occlusion group. In conclusion, it was demonstrated that anterior reverse bite in the primary dentition clearly affects the paths of habitual opening movements.

Analysis of Variance↗
PubMed2002

The effect of genomic position on reversion of a lac frameshift mutation (lacIZ33) during non-lethal selection (adaptive mutation).

In a system described by Cairns and Foster, starvation of a particular leaky lac mutant (lacIZ33) in the presence of lactose appears to direct mutation in non-growing cells to sites that allow growth (adaptive mutation). This behaviour requires that the lac operon be located on an F' plasmid. This position effect was investigated by placing the mutant lac operon at many sites in the genome of Salmonella enterica (Typhimurium; LT2) and testing reversion behaviour. Genomic position did not affect reversion during non-selective growth. When lac was at any of 550 chromosomal sites, starvation caused little or no enhancement of reversion. In the 28 strains with the lac on Salmonella's conjugative plasmid (pSLT), selection enhanced reversion strongly, just as seen for strains with lac on an F' plasmid. In 46 strains, the lac operon was inserted within a small chromosomal duplication, and selection stimulated RecA-dependent partial reversion by simple amplification (about 8x) of the mutant lac region. The position of lac on a conjugative plasmid is important to reversion because it allows more frequent gene duplication and amplification. These events are central to growth and reversion under selection because they increase the number of replicating lac alleles within each developing revertant clone.

Adaptation, Biological↗
PubMed2002

Prospective analysis of quality of life after reversal of a defunctioning loop ileostomy.

OBJECTIVE: To measure changes in patients' quality of life following reversal of a defunctioning ileostomy in patients who had a curative anterior resection for rectal cancer. PATIENTS AND METHODS: Twenty consecutive patients undergoing reversal of a loop ileostomy following low anterior resection for primary rectal cancer participated. They answered three quality of life questionnaires: the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38, and the SF-36. Questionnaires were answered before reversal, on discharge home, and at 3 and 6 months postoperatively. RESULTS: Reversal of the defunctioning ileostomy resulted in significant improvements in global quality of life, physical function, social function, role-physical and energy-vitality scores. Post-operative diarrhoea and frequency improved over six months, but one third of patients had mild incontinence of faeces which did not improve with time. Emotional function, mental health, future perspective, perception of body image and general health perception did not change significantly after reversal. There was a significant negative correlation between defaecation-related problems, global quality of life and body image. CONCLUSION: Reversal of a defunctioning loop ileostomy improves most patients' overall quality of life. Therefore, once it is considered safe to reverse a stoma, an early operation may give the patient a longer time with an improved quality of life.

Journal Article↗
PubMed2001

Possible regulation of telomerase activity by transcription and alternative splicing of telomerase reverse transcriptase in human melanoma.

To investigate the regulatory mechanisms of telomerase activity in human melanoma cells, we assessed the enzyme's catalytic activity and the expression of the telomerase subunits, the human telomerase RNA, the human telomerase-associated protein, and the human telomerase reverse transcriptase, in 52 melanoma lesions. Eight normal skin specimens were also studied. Telomerase activity was detected in 84.6% of melanomas, whereas all skin specimens were telomerase negative. Human telomerase-associated protein mRNA and human telomerase RNA were constitutively expressed in all melanoma and skin specimens. Although at a variable level of expression, human telomerase reverse transcriptase mRNA was detected in all but one melanomas, whereas it was never present in skin samples. Reverse transcriptase-polymerase chain reaction experiments were performed using primers within the reverse transcriptase domain of human telomerase reverse transcriptase and revealed the presence of multiple alternatively spliced transcripts in melanoma specimens. Among the 44 telomerase-positive melanomas, one showed the full-length transcript alone whereas in all other specimens a full-length message was present with different combinations of alternatively spliced variants. In these tumors the expression of the full-length transcript was generally equal to or higher than that of the alternatively spliced variants. The ratio full-length transcript to alternatively spliced species ranged from 0.6 to 5.26, with a median value of 1.18. Among the seven telomerase-negative melanomas, one displayed the beta deletion transcript alone, whereas in the remaining six tumors weak expression of the full-length transcript and a more abundant level of alternatively spliced transcripts were found. In these cases human telomerase reverse transcriptase ratio ranged from 0.09 to 1.1, with a median value of 0.40. The results suggest that transcription and alternative splicing of human telomerase reverse transcriptase are regulatory mechanisms controlling telomerase activity in melanoma.

Alternative Splicing↗
PubMed2005

Urea clearance in dysfunctional catheters is improved by reversing the line position despite increased access recirculation.

BACKGROUND: Problematic or dysfunctional hemodialysis (HD) catheters are routinely reversed to achieve adequate blood flow for dialysis delivery. The purpose of the study is to determine the effect of varying blood pump speed (Qb) on access recirculation (AR), and urea clearance (K) in dysfunctional catheters in the normal and reversed positions. METHODS: Nineteen HD patients with tunneled cuffed catheters (5 functional and 14 dysfunctional catheters) were included; dysfunctional catheters are defined as the inability to attain a Qb of 300 mL/min or greater on 2 consecutive HD runs. AR and K measurements were obtained systematically for each catheter in the normal and reversed positions at increasing Qbs. K was measured using the ionic dialysance technique. RESULTS: In functional catheters, AR in the normal position was 0% and increased to 15% +/- 13% when reversed. Dysfunctional catheters had a greater AR of 25% +/- 16% when reversed. In functional catheters, there was no evidence of an increase in AR with increasing Qb irrespective of position. Similarly, there was no relationship between increasing AR and greater Qbs (r 2 = 0.10) in dysfunctional catheters. In dysfunctional catheters, when reversed, mean K increased from 128 +/- 10 mL/min at a Qb of 200 mL/min to 157 +/- 38 mL/min at maximal Qb (P < 0.05). CONCLUSION: We show that at increasing Qbs, K is improved in both functional and dysfunctional catheters. Data from the study are used to describe a nomogram to determine minimum Qb for a dysfunctional catheter in reversed position to maximize K.

Aged↗
PubMedDate not supplied

[Placental morphometry in pregnancies with reversed enddiastolic flow in the umbilical artery or fetal aorta].

BACKGROUND: Fetuses with a reversed enddiastolic flow in the umbilical artery and/or aorta are at risk pregnancies and show a higher incidence of perinatal morbidity and mortality. The aim of this study was to evaluate the pathological changes in the terminal villous tree in fetuses with a reverse flow in the fetal aorta or umbilical artery. MATERIALS AND METHODS: In this retrospective study, 16 cases with a reverse flow in the fetal aorta or umbilical artery (Gr. 1) were compared with gestational age matched 16 healthy pregnant women (Gr. 2). The following morphometric parameters were evaluated in 50 sections in each placenta (1600 measurements): mean vessel diameter, volume density of the villous tissue, stem villi and terminal villi. Measurements were performed using a computerized Video Image Analysis system. RESULTS: The mean gestational age at birth was similar in both groups (30 + 4 weeks gestation vs. 30 + 6 weeks gestation, respectively, for Gr. 1 and Gr. 2). The birth weights (985 g vs. 1780 g) and the placental weights (216 g vs. 385 g) were significantly lower in the reverse flow group. There was a significant reduction in the proportion of total villous tissue (19 % versus 45 %) and in the diameter of tissue at the terminal villi (2.1 % versus 7.6 %) in the reverse flow group. Although the mean number of vessels at the terminal villi was lower than the control group (4.1 versus 5.6), the mean and total areas of the vessels were not different. CONCLUSION: Our observations showed a significant association between the placental morphometric parameters and reversed enddiastolic flow in the umbilical artery or fetal aorta. The reduced number of functional placental units is responsible for the diminished exchange function of the placental vessels in "reverse flow" cases. This could partially explain the adverse outcome in this clinical situation.

Adult↗