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At least 811 records · Page 45Linked to original sources
PubMed2002

Acute myeloid leukemia (AML) having evolved from essential thrombocythemia (ET): distinctive chromosome abnormalities in patients treated with pipobroman or hydroxyurea.

ET is a chronic myeloproliferative disorder rarely evolving into AML, sometimes preceded by a myelodysplastic syndrome (MDS). Such transformations mostly occur in patients treated with radiophosphorous ((32)P) or alkylating agents, especially busulfan. Recently, concern has also arisen about the long-term safety of hydroxyurea (HU). Pipobroman (PI), a well tolerated and simple to use drug, constitutes a valid alternative to those cytoreductive treatments. The present study reports on 155 ET patients treated at our institution from 1985 to 1995, and monitored until December 2000. A good control of thrombocytosis was achieved with PI as the only treatment in 106 patients and with HU in 23 patients. Twenty-six patients received no treatment. After a median follow-up of 104 months, seven patients (four treated with HU, and three with PI) developed AML whereas one patient treated with PI developed MDS. A significant difference in progression-free survival was observed between HU- and PI-treated patients (P = 0.004). A short-arm deletion of chromosome 17 was most frequently detected in HU-treated patients, while a long-arm trisomy of chromosome 1 and a monosomy 7q were seen in PI-treated patients. No TP53 mutation was discovered in the six patients studied (two HU-treated and four PI-treated). We conclude that these cytogenetic abnormalities are not linked to the natural history of the disease, but rather that they might be induced by the cytoreductive treatment.

Acute Disease↗
PubMed2005

The evolving role of alemtuzumab in management of patients with CLL.

New insights into prognostic markers and the pathophysiology of chronic lymphocytic leukemia (CLL) are beginning to change the concept of CLL treatment. Alemtuzumab has evolved as a potent and effective therapeutic option for patients with CLL. Specifically, alemtuzumab has demonstrated substantial efficacy in fludarabine-refractory patients and has shown impressive responses when administered subcutaneously in first-line therapy. A group of experts gathered to discuss new data related to the use of alemtuzumab in CLL and to assess its place in the rapidly changing approach to treating patients with this disease. The main goals of this program were to update the management guidelines that were previously developed for alemtuzumab-treated patients and to provide community oncologists with guidance on the most effective way to integrate alemtuzumab into a CLL treatment plan.

Alemtuzumab↗
PubMed1999

Interstitial laser coagulation in the treatment of benign prostatic hyperplasia using a diode laser system: results of an evolving technology.

Interstitial laser coagulation (ILC) treatment is a recent technique in the treatment of BPH that is evolving rapidly. The results of a prospective randomised study vs transurethral resection of the prostate (TURP) is presented as well as results of patients treated with a temperature sensing laser system. The first study included 44 patients treated in a prospective randomised study (randomisation ILC vs TURP=2:1) comparing changes in objective and subjective parameters. In the second part of the study the outcome of the treatment of 34 patients with BPH using ILC performed with a temperature-sensing laser system are presented. The clinical outcome at 12, 26, 52 and 104 weeks was evaluated with symptom scores, quality of life measures, changes in voided volume, post void residual, and peak flow rate. In addition changes in prostate volume and urodynamic parameters at half a year follow-up are presented. In this randomised study patients improved markedly at any time during follow-up. In the ILC group there was a significant and persisting subjective improvement whereas the improvements in the TURP group were even more significant. The changes in voiding parameters, including changes in pressure-flow parameters, are superior in the TURP group compared to the changes in the ILC group. The retreatment rate for the ILC group is 21% compared to 7% in the TURP group, no patient with incontinence was documented in either group, while only one patients in the TURP group developed a urethral stricture. In the second part of the study, the clinical improvements following laser therapy using the temperature sensing treatment mode were more pronounced in voiding parameters when compared to those of the randomised laser group. Lower energy interstitial laser treatment of the prostate results in a significant improvement of all clinical parameters that are inferior to improvement following transurethral resection of the prostate. When using a temperature sensing system, the objective results of laser treatment improved and seem to be more durable.

Journal Article↗
PubMed2006

F-wave amplitudes indicate evolving spinal autonomy during spontaneous recovery of hindlimb function in rat spinal cord contusion.

STUDY DESIGN: Experimental rat model of spinal cord contusion. OBJECTIVES: To reveal the extent of spinal autonomy contributing to recovery of hindlimb function. SETTING: Experimental laboratory of a neurosurgical university department. METHODS: F-wave amplitudes as a probe for spinal cord excitability were recorded from both sciatic nerves (lumbar segments L2-L5) before and after an experimental spinal cord contusion performed in the lower thoracic spinal cord. Additionally, transcranial electrically motor evoked potentials from the hindlimbs and cerebral somatosensory potentials evoked by sciatic nerve stimulation were recorded. Clinical evaluation of hindlimb function was done regularly for survival periods of 3 and 50 days, respectively. Electrophysiological testing was performed immediately prior and after lesioning of the cord and at the endpoint of survival periods. RESULTS: Hindlimb function recovered from a mean Basso-Beattie-Bresnahan score of 5.6 on day 1 to 9.2 on day 3 (3-day-survivors) and from 7.7 to 17.2 on day 50 (50-day-survivors). This was accompanied by a significant increase of F-wave amplitudes on day 50 compared to baseline values, whereas amplitudes of somatosensory and motor-evoked potentials remained significantly depressed. CONCLUSION: Recovery of hindlimb function may at least in part be attributed to evolving spinal autonomy, which can be assessed by F-wave amplitudes.

Action Potentials↗
PubMed2005

Structure and evolution of the extrinsic proteins that stabilize the oxygen-evolving engine.

PsbO, PsbP and PsbQ are the extrinsic proteins associated with the oxygen-evolving (OE) engine of all known higher plants. However their presence is not constant throughout all known oxy-photosynthetic organisms. For this reason, comparative analyses of the sequence and the structure of these proteins in different species from prokaryotes to eukaryotes may allow unravelling of the evolutionary track that they have followed and infer new hints about their function in the OE complex. The results show that PsbP and PsbQ present different evolutionary profiles, and that PsbQ is more closely associated to PsbO and probably to the manganese stabilizing role assigned to this protein.

Evolution, Molecular↗
PubMed2006

Measurement of cell migration in response to an evolving radial chemokine gradient triggered by a microvalve.

We describe a novel chemotaxis assay based on the microvalve-actuated release of a chemoattractant from a cell-free microchamber into a cell-containing microchamber. The microvalve chemotaxis device (microVCD) was placed on the stage of a conventional inverted microscope to obtain time-lapse micrographs of neutrophils migrating in a radially-symmetric evolving gradient of the chemotactic factor CXCL8/Interleukin-8. A fluorescent tracer was added to the CXCL8 solution to visualize the evolution of the gradient profile, so that at each time point the cell positions could be assigned CXCL8 concentration values. Tracking of individual neutrophils for 90 minutes showed that (a) the neutrophil migratory response is, on average, radially directed towards the CXCL8 source; (b) significant non-radial displacements occur frequently; and (c) there is considerable heterogeneity in the migration speeds and directions amongst the neutrophil population. A custom-made imaging analysis tool was used to extract measurements of migratory behavior such as speed, velocity along the gradient's radial axis, and the cosine of the turning angle as a function of CXCL8 concentration. The microVCD can be easily adapted to study the migratory behavior of cultured cells other than neutrophils.

Chemotaxis, Leukocyte↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed1981

Properties of oxygen-evolving photosystem-II particles from Phormidium laminosum, a thermophilic blue--green alga.

1. O2-evolving Photosystem-II particles from the thermophilic blue--green alga Phormidium laminosum contained 1 mol of Mn/13--17 mol of chlorophyll a compared with 1 mol of Mn/65--75 mol of chlorophyll a in unfractionated membranes. 2. At least two-thirds of the Mn in the Photosystem-II particles was removed by mild heating and by treatment with Tris or EDTA, with concomitant loss of O2 evolution. However, irreversible inactivation was also caused by washing in buffers without MgCl2, and this inactivation was not accompanied by a corresponding loss of Mn. 3. Bivalent cations (Mg2+ or Ca2+), Cl- or Br- ions and at least 20% (v/v) glycerol were required for maximum stability of O2 evolution. 4. The Photosystem-II particles were enriched in high-potential cytochrome b-559 (1 mol of cytochrome/50--60 mol of chlorophyll a) and in component C-550, and had a photosynthetic-unit size of 40--70 molecules of chlorophyll a. 5. The absorption spectrum at 77 K showed a preponderance of shorter-wavelength forms of chlorophyll a in the Photosystem-II particles, and in the fluorescence emission spectrum at 77 K there were major chlorophyll fluorescence bands at 684 nm and 695 nm, with almost no fluorescence in the far-red region. 6. Analysis of the lipid and protein contents showed that the Photosystem-II particles were not chemically pure (for example, all of the membrane-bound cytochromes and cytochrome c-549 were present), but their high O2-evolution activity and good optical properties make them useful for functional studies on Photosystem-II and O2 evolution.

Chloroplasts↗
PubMed1983

A requirement for Ca2+ in the extraction of O2-evolving Photosystem 2 preparations from the cyanobacterium Anacystis nidulans.

Ca2+ has been shown to be essential for the retention of maximal O2-evolving activity in Photosystem 2 particles extracted by using dodecyldimethylamine oxide from Anacystis nidulans thylakoids. The effect cannot entirely be mimicked by using Mg2+. Ca2+ stimulates electron transport from diphenylcarbazide to 2,6-dichloroindophenol catalysed by lead-inhibited cation-free preparations, showing the presence of two cation-binding sites in these particles. Photosystem 2 preparations extracted in Ca2+-containing buffer show the presence of three polypeptides at mol. wt. 30000, 33000 and 36000, which are absent or much decreased in preparations extracted in Mg2+-containing buffer. The calmodulin antagonist chlorpromazine inhibits activity of the Photosystem 2 preparation, suggesting the presence of a Ca2+-binding protein.

Calcium↗
PubMed1989

The catalytic consequences of experimental evolution. Transition-state structure during catalysis by the evolved beta-galactosidases of Escherichia coli (ebg enzymes) changed by a single mutational event.

1. The first chemical step in the hydrolysis of galactosylpyridinium ions by the evolvant ebg enzyme is less sensitive to leaving-group acidity than in the case of the wild-type ebg enzyme, implying less glycone-aglycone-bond fission at the transition state. 2. The first chemical step in the hydrolysis of aryl galactosides by ebg enzyme is probably less sensitive to leaving-group acidity than in the case of ebg enzyme, possibly as a consequence of resulting in more effective proton donation to the leaving aglycone. 3. alpha-Deuterium kinetic isotope effects of 1.1(0) and beta-deuterium kinetic isotope effects of 1.0(0) were measured for the hydrolysis of galactosyl-enzyme intermediates derived from ebg and ebg enzymes: these effects are not compatible with reaction of the sugar ring through a 4C1-like conformation, or with an ionic glycosyl-enzyme intermediate. 4. The variation with pH of steady-state kinetic parameters for hydrolysis of p-nitrophenyl galactoside by ebg and ebg enzymes and of 3-methylphenyl beta-galactoside, 3,4-dinitrophenyl beta-galactoside and beta-galactosyl-3-bromopyridinium ion by ebg enzyme was measured. The steep, non-classical, fall in activity against p-nitrophenyl galactoside at low pH observed with ebg and ebg enzymes is not observed with ebg enzymes.

Catalysis↗
PubMed1980

Chronic lability of arterial pressure in the rat does not evolve into hypertension.

1. In rats, electrolytic lesions of the A2 group of catecholamine neurons result in lability of arterial pressure without hypertension. 2. To establish whether labile arterial pressure, when chronic, will lead to fixed hypertension, we placed lesions in the A2 area of adult male Sprague-Dawley rats and measured mean arterial pressure, heart rate and their variability (expressed as the standard deviation) 11 months later. Controls were age-matched, unoperated or sham-operated rats. 3. In rats with A2 lesions: (a) the mean arterial pressure was lower (103 +/- 7.5 mmHg; n = 6; P < 0.05) than in sham-operated (123 +/- 4.7 mmHg; n = 4) or unoperated (120 +/- 3.1 mmHg; n = 9) controls; (b) the standard deviation of mean arterial pressure was higher (16 +/- 1.8 mmHg; P < 0.001) than in sham-operated (5 +/- 0.7 mmHg) or unoperated controls (7 +/- 0.6 mmHg); (c) the mean and standard deviation of heart rate did not differ between groups. No histopathological changes were detected in the A2 group. 4. Chronic lability of arterial pressure does not evolve into sustained hypertension nor does it induce systemic lesions.

Animals↗
PubMed1998

Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia evolving from MDS.

One hundred and five consecutive primary high-risk myelodysplastic syndromes (MDS) or secondary acute myeloid leukaemia (sAML) evolving from MDS (performance status 0-3, ECOG) entered this study. Induction chemotherapy (CT) consisted of idarubicine 12 mg/m2 i.v. on days 1 and 2, etoposide 60 mg/m2/12h i.v. for 5d, Ara-C 120 mg/ m2/12h i.v. for 5d (one or two courses). Patients were randomized to receive or not G-CSF (5 microg/kg/d subcutaneously 48 h after the end of CT). 52 cases underwent CT alone and 53 CT+G-CSF. The CT+ G-CSF patients had a significantly shorter duration of neutropenia (8 nu 16d) with a lower incidence of infections and significantly better responses (CR+PR: 74% v 52%, P<0.05). 40 patients entered CR: 17 with CT and 2 3 with CT+G-CSF. Responders underwent two consolidation courses with the same CT, followed by high-dose Ara-C (2 g/m2 every 12h for 3 d). Most CRs were clonal. At present 21 responders have relapsed (median relapse-free survival 4 5 months). Eight responders received an allo-BMT, six are alive in CR 7-57 months post-transplant. Therefore allo-BMT only increases the chance of a long survival and possible cure. In conclusion, CT+G-CSF did not prolong either CR duration or survival; the growth factor support, however, increased the number of allo-transplantable cases by inducing higher remission rates and improving clinical conditions.

Acute Disease↗
PubMed2003

Lichen planus pemphigoides evolving into pemphigoid nodularis.

Lichen planus pemphigoides (LPP) and pemphigoid nodularis are rare clinical variants of bullous pemphigoid (BP), which are characterized by histological findings of lichen planus (LP) and nodular prurigo, respectively, and the finding of linear deposits of IgG and/or C3 at the basement membrane zone in perilesional skin. In both cases bullae may arise at the site of pre-existing LP-like or nodular prurigo-like eruptions, and clinically uninvolved skin. The disease spectrum of LPP and pemphigoid nodularis differs from that of classical BP phenotype, and their presentations are often indolent. LPP may predominantly affect a younger age group and is responsive to standard treatments used in acquired autoimmune bullous diseases, while pemphigoid nodularis is more common in elderly women and is relatively resistant to therapy. We describe a patient who had LPP for nearly two decades and subsequently developed a nodular eruption with a concurrently detected antibullous pemphigoid antigen 2 (BP180) autoantibody. His overall clinicopathological features were indicative of LPP evolving into another BP variant, pemphigoid nodularis.

Autoantigens↗
PubMed2003

Evolving patterns of tobacco use in northern Sweden.

BACKGROUND AND OBJECTIVES: Cross-sectional data from northern Sweden suggest that the increased use of Swedish moist snuff (snus) may have contributed to a decline in the prevalence of smoking, especially amongst men. This study describes the evolving patterns of tobacco use in this population over the period 1986-1999. DESIGN: This is a prospective follow-up study of 1651 men and 1756 women, aged 25-64 years, who were enrolled in the northern Sweden MONICA project (entry in 1986, 1990, 1994) and who were followed-up in 1999. Information on tobacco use at entry and at follow-up was used to describe the stability of tobacco use over a period of 5-13 years ending in 1999. RESULTS: Snus was the most stable form of tobacco use amongst men (75%); only 2% of users switched to cigarettes and 20% quit tobacco altogether. Smoking was less stable (54%); 27% of smokers were tobacco-free and 12% used snus at follow-up. Combined use (smoking and snus) was the least stable (39%), as 43% switched to snus and 6% switched to cigarettes. Former users of both products were much less stable than former users of either cigarettes or snus. The stability of smoking amongst women was 69%, which was higher than that amongst men (P < 0.05). CONCLUSIONS: The use of snus played a major role in the decline of smoking rates amongst men in northern Sweden. The evolution from smoking to snus use occurred in the absence of a specific public health policy encouraging such a transition and probably resulted from historical and societal influences.

Adult↗
PubMed2000

Characterization of the O-antigen gene clusters of Yersinia pseudotuberculosis and the cryptic O-antigen gene cluster of Yersinia pestis shows that the plague bacillus is most closely related to and has evolved from Y. pseudotuberculosis serotype O:1b.

One of the most virulent and feared bacterial pathogens is Yersinia pestis, the aetiologic agent of bubonic plague. Characterization of the O-antigen gene clusters of 21 serotypes of Yersinia pseudotuberculosis and the cryptic O-antigen gene cluster of Y. pestis showed that the plague bacillus is most closely related to and has evolved from Y. pseudotuberculosis serotype O:1b. The nucleotide sequences of both gene clusters (about 20.5 kb each) were determined and compared to identify the differences that caused the silencing of the Y. pestis gene cluster. At the nucleotide sequence level, the loci were 98.9% identical and, of the 17 biosynthetic genes identified from the O:1b gene cluster, five were inactivated in the Y. pestis cluster, four by insertions or deletions of one nucleotide and one by a deletion of 62 nucleotides. Apparently, the expression of the O-antigen is not beneficial for the virulence or to the lifestyle of Y. pestis and, therefore, as one step in the evolution of Y. pestis, the O-antigen gene cluster was inactivated.

Amino Acid Sequence↗
PubMed2000

Lessons learned from the Decision Board: a unique and evolving decision aid.

One session of the conference was devoted to the presentation of different types of decision aids. This paper reports the experience and lessons learned through the development and use of the Decision Board. This is a uniquely interactive decision aid administered by the clinician during the medical consultation. The instrument has been developed in a number of clinical contexts, primarily regarding treatment options for cancer patients. Studies have shown the instrument to improve patient understanding and facilitate the shared decision-making process. Randomized trials are ongoing, evaluating the addition of the Decision Board to the traditional medical consultation. The instrument continues to evolve to meet patients' need for information and flexibility in presentation. Computer-based versions of the Decision Board are currently being developed.

Journal Article↗
PubMed2002

Purification and catalytic properties of a CO-oxidizing:H2-evolving enzyme complex from Carboxydothermus hydrogenoformans.

From the membrane fraction of the Gram-positive bacterium Carboxydothermus hydrogenoformans, an enzyme complex catalyzing the conversion of CO to CO2 and H2 was purified. The enzyme complex showed maximal CO-oxidizing:H2-evolving enzyme activity with 5% CO in the headspace (450 U per mg protein). Higher CO concentrations inhibited the hydrogenase present in the enzyme complex. For maximal activity, the enzyme complex had to be activated by either CO or strong reductants. The enzyme complex also catalyzed the CO- or H2-dependent reduction of methylviologen at 5900 and 180 U per mg protein, respectively. The complex was found to be composed of six hydrophilic and two hydrophobic polypeptides. The amino-terminal sequences of the six hydrophilic subunits were determined allowing the identification of the encoding genes in the preliminary genome sequence of C. hydrogenoformans. From the sequence analysis it was deduced that the enzyme complex is formed by a Ni-containing carbon monoxide dehydrogenase (CooS), an electron transfer protein containing four [4Fe-4S] clusters (CooF) and a membrane bound [NiFe] hydrogenase composed of four hydrophilic subunits and two membrane integral subunits. The hydrogenase part of the complex shows high sequence similarity to members of a small group of [NiFe] hydrogenases with sequence similarity to energy conserving NADH:quinone oxidoreductases. The data support a model in which the enzyme complex is composed of two catalytic sites, a CO-oxidizing site and a H2-forming site, which are connected via a different iron-sulfur cluster containing electron transfer subunits. The exergonic redox reaction catalyzed by the enzyme complex in vivo has to be coupled to energy conservation, most likely via the generation of a proton motive force.

Acetylene↗