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At least 145 records · Page 8Linked to original sources
PubMed2003

Cell cycle-regulated transcription through the FHA domain of Fkh2p and the coactivator Ndd1p.

Recent studies in Saccharomyces cerevisiae by using global approaches have significantly enhanced our knowledge of the components involved in the transcriptional regulation of the cell cycle. The Mcm1p-Fkh2p complex, in combination with the coactivator Ndd1p, plays an important role in the cell cycle-dependent expression of the CLB2 gene cluster during the G2 and M phases ([4-7]; see [8-10]for reviews). Fkh2p is phosphorylated in a cell cycle-dependent manner, and peak phosphorylation occurs coincidentally with maximal expression of Mcm1p-Fkh2p-dependent gene expression. However, the mechanism by which this complex is activated in a cell cycle-dependent manner is unknown. Here, we demonstrate that the forkhead-associated (FHA) domain of Fkh2p directs cell cycle-regulated transcription and that the activity of this domain is dependent on the coactivator Ndd1p. Ndd1p was found to be phosphorylated in a cell cycle-dependent manner by Cdc28p-Clb2p, and, importantly, this phosphorylation event promotes interactions between Ndd1p and the FHA domain of Fkh2p. Furthermore, mutation of the FHA domain blocks these phosphorylation-dependent interactions and abolishes transcriptional activity. Our data therefore link the transcriptional activity of the FHA domain with cell cycle-dependent phosphorylation of the coactivator Ndd1p and reveal a mechanism that permits precise temporal activation of the Mcm1p-Fkh2p complex.

Blotting, Western↗
PubMed2005

Inhibitory action of L-type Ca2+ current by paeoniflorin, a major constituent of peony root, in NG108-15 neuronal cells.

The effects of paeoniflorin, a glycoside isolated from the root of Paeonia lactiflora, on ion currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15 were investigated. Paeoniflorin (1-300 microM) reversibly produced an inhibition of L-type voltage-dependent Ca2+ current (I(Ca,L)) in a concentration-dependent manner. Paeoniflorin caused no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC50 value of paeoniflorin-induced inhibition of I(Ca,L) was 14 microM. However, neither adenosine deaminase (1 U/ml) nor 8-cyclopentyl-1, 3-dipropylxanthine (10 microM) could reverse the inhibition by paeoniflorin of I(Ca,L). Paeoniflorin (30 microM) shifted the steady-state inactivation curve of I(Ca,L) to more negative membrane potentials by approximately -10 mV. It also prolonged the recovery of I(Ca,L). The inhibitory effect of paeoniflorin on I(Ca,L) exhibited tonic and use-dependent characteristics. Paeoniflorin could effectively suppress I(Ca,L) evoked by action potential waveforms. Paeoniflorin at a concentration of 30 microM produce a slight inhibition of voltage-dependent Na+ current and delayed rectifier K+ current. Under current-clamp configuration, unlike adenosine, this compound decreased the firing of action potentials. Taken together, this study indicates that paeoniflorin can block L-type Ca2+ channels in NG108-15 cells in a mechanism unlinked to the binding to adenosine receptors. The effects of paeoniflorin on ion currents may partly, if not entirely, contribute to the underlying mechanisms through which it affects neuronal or neuroendocrine function.

Action Potentials↗
PubMed2004

The safety and efficacy of multiple consecutive cryo lesions in canine pulmonary veins-left atrial junction.

OBJECTIVE: The purpose of the study is to evaluate the safety and efficacy of multiple cryo lesions in canine pulmonary veins-left atrial junction. BACKGROUND: The use of radiofrequency to achieve electrical isolation of the pulmonary veins (PVs) has been associated with PV stenosis. No information is currently available concerning the safety and the electrophysiological effects of multiple and consecutive cryo applications at the PV-left atrial junction. METHODS: Liquid N(2)O was delivered into semi-compliant 15 to 22-mm-diameter balloons. In 13 dogs weighing 34 +/- 2 kg, one to four consecutive cryo lesions were randomly applied to each PV for 3 minutes in 6-minute intervals. The pre- and post-PV sizes were recorded by angiography. Electrogram activity and pacing thresholds were recorded before and after cryo. PV patency and the PV-atrial tissue characteristics were evaluated grossly and histologically. RESULTS: Pacing capture was not possible with 10 mA postablation in 26/46 (57%) electrodes, and in 20 (43%) electrodes pacing threshold increased from 1.6 +/- 1.7 mA to 7.8 +/- 3.2 mA. The total elimination of recorded electrograms was noted in 22%, 29%, and 18% following 1, 2, and 3 cryo lesions respectively. After 4 lesions this value increased to 53%. No significant changes in PV diameter were recorded in any of the veins pre vs the terminal study. The PVs and PV-atrial interface tissue were soft, compliant, and without collagen or cartilaginous tissue. There was no hemoptysis in any of the dogs. CONCLUSION: In this study, cryo balloon technology is effective and safe regardless of the number of lesions applied and the freezing temperatures achieved. Four consecutive cryo applications result in a significant increase in pacing threshold and a decrease in activity of local atrial electrograms.

Analysis of Variance↗
PubMed2004

Line shape considerations in ultrafast 2D NMR.

We have recently proposed and demonstrated an approach that enables the acquisition of 2D nuclear magnetic resonance (NMR) spectra within a single scan. The approach is based on spatially encoding the spins' evolution along the indirect domain with the aid of a magnetic field gradient, and subsequently decoding this information numerous times over the course of the signal acquisition while spins are subject to a train of gradient echoes. The present paper discusses further considerations pertaining the 2D line shapes arising from this new way of collecting NMR data. Specific issues that are hereby addressed include (i) the effects introduced by fast relaxation onto the spatial encoding process, particularly the line widths and line shapes that will then arise in the frequency domain; (ii) approaches capable of correcting for the mixed-phase kernels resulting in these fast-relaxation cases, corresponding in essence to spatially encoded analogs of the TPPI and hypercomplex time-domain acquisition procedures; (iii) the enveloping characteristics imposed by the use of discrete excitation pulses on the attainable spectral widths along the indirect domain; and (iv) an analysis of the signal-to-noise characteristics of the methodology, with experimental corroborations of theoretical predictions and an illustration of the method's capabilities to analyze protein solutions in the mM-range concentration.

Algorithms↗
PubMed2006

Indirect detection of nitrogen-14 in solids via protons by nuclear magnetic resonance spectroscopy.

This Communication describes the indirect detection of 14N nuclei (spin I=1) in solids by nuclear magnetic resonance (NMR) spectroscopy. The two-dimensional correlation method used here is closely related to the heteronuclear multiple quantum correlation (HMQC) experiment introduced in 1979 to study molecules in liquids, which has recently been used to study solids spinning at the magic angle. The difference is that the coherence transfer from neighboring 1H nuclei to 14N is achieved via a combination of J couplings and residual dipolar splittings (RDS). Projections of the two-dimensional correlation spectra onto the 14N dimension yield powder patterns which reflect the 14N quadrupolar interaction. In contrast to the indirect detection of 14N via 13C nuclei that was recently demonstrated [Gan, J. Am. Chem. Soc. 128 (2006) 6040; Cavadini et. al., J. Am. Chem. Soc., 128 (2006) 7706], this approach may benefit from enhanced sensitivity, and does not require isotopic enrichment in 13C, although the 1H line-widths may have to be reduced upon selective deuteration.

Glycine↗
PubMed2006

Pouch-anal anastomosis vs straight ileoanal anastomosis in pediatric patients: a meta-analysis.

BACKGROUND: Restorative proctocolectomy is the treatment of choice for pediatric patients with refractory colitis, inherited polyposis syndromes, and some with colonic aganglionosis. Evidence concerning the optimal method of reconstruction is, however, sparse. METHODS: Studies comparing outcomes from ileal pouch-anal anastomosis (IPAA) and straight ileoanal anastomosis (SIAA) were identified by searching Medline, Ovid, and Embase. Suitable studies were selected and data extracted for meta-analysis. RESULTS: Of 13 studies identified by literature search, 5 satisfied the inclusion criteria, comprising a total of 306 patients, 86 of whom (28.1%) underwent SIAA, and the remainder, IPAA. Pouch failure was more common in the SIAA group (odds ratio, 3.21; confidence interval, 1.24-8.34), as were abdominal salvage procedures (odds ratio, 9.5; confidence interval, 3.14-28.77). Short-term adverse events were similar between the 2 groups, with the exception of perianal sepsis, the higher frequency of which, in SIAA, just reached statistical significance. Bowel frequency was lower in the IPAA patients, although few studies presented functional data in a comparable form. CONCLUSIONS: There are few good-quality studies that compare the outcomes from SIAA and IPAA, meaning that caution should be exercised in the generalization of the results of this meta-analysis, which suggests pouch procedures to be favorable in terms of reconstruction survival and functional outcome.

Adenomatous Polyposis Coli↗
PubMed2006

Identification of two types of ATP-sensitive K+ channels in rat ventricular myocytes.

The ATP-sensitive K(+) (K(ATP)) channels are known to provide a functional linkage between the electrical activity of the cell membrane and metabolism. Two types of inwardly rectifying K(+) channel subunits (i.e., Kir6.1 and Kir6.2) with which sulfonylurea receptors are associated were reported to constitute the K(ATP) channels. In this study, we provide evidence to show two types of K(ATP) channels with different biophysical properties functionally expressed in isolated rat ventricular myocytes. Using patch-clamp technique, we found that single-channel conductance for the different two types of K(ATP) channels in these cells was 57 and 21 pS. The kinetic properties, including mean open time and bursting kinetics, did not differ between these two types of K(ATP) channels. Diazoxide only activated the small-conductance K(ATP) channel, while pinacidil and dinitrophenol stimulated both channels. Both of these K(ATP) channels were sensitive to block by glibenclamide. Additionally, western blotting, immunochemistry, and RT-PCR revealed two types of Kir6.X channels, i.e., Kir6.1 and Kir6.2, in rat ventricular myocytes. Single-cell Ca(2+) imaging also revealed that similar to dinitrophenol, diazoxide reduced the concentration of intracellular Ca(2+). The present results suggest that these two types of K(ATP) channels may functionally be related to the activity of heart cells.

Animals↗
PubMed2005

Smoking habit and genetic factors associated with lung cancer in a population highly exposed to arsenic.

In order to find some relationship between genetic differences in metabolic activation and detoxification of environmental carcinogens and host susceptibility to chemically induced cancers, we have investigated the distribution of the GSTM1 null genotype and CYP450 *1A1 MspI polymorphism in lung cancer patients and healthy volunteers of the second region in the north of Chile highly exposed to arsenic. The main sources of environmental arsenic exposure in Chile are copper smelting and drinking water, specially in the second region, the most important copper mining region in the world that shows the highest lung cancer mortality rate in the country (35/100.00). The population of Antofagasta, the main city of the region was exposed between 1958 and 1970 to arsenic concentrations in drinking water of 860 microg/m3, presently declining to 40 microg/m3. For men the MspI CYP1A1 *2A genotype was associated with a highly significant estimated relative lung cancer risk (O.R. = 2.60), but not GSTM1 by itself. The relative lung cancer risk for the combined 2A/null GSTM1 genotypes was 2.51, which increased with the smoking habits (O.R. = 2.98). In the second region the cancer mortality rate for As associated cancers, might be related at least part to differences in As biotransformation. In this work we demonstrate that genetic biomarkers such as CYP1A1 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with higher risk for lung cancer, due to arsenic exposure.

Adult↗
PubMed2005

Complications and troubleshooting of sacral neuromodulation therapy.

As evident from the authors' series, the complications of sacral neuromodulation have changed with the introduction of the tined lead and the placement of the generator over the back. In the earlier series, most complications were related to pain at the generator site, which was rare in the authors' series. The posterior location of the generator seems to be better tolerated than the anterior location, which could explain the rare need for revisions for pain at the generator site. Lead migration was observed in 8.4% of the original sacral neuromodulation study group series. This was seen rarely in the authors' series in either stage-one or stage-two revisions. As part of the routine work-up of patients who present with decreased function after a successful period response in stage two, the authors obtain a lateral radiograph of the sacrum; the authors have made the diagnosis of lead migration rarely (1/130; 0.6%). Spinelli and colleagues reported on the use of the tined lead in 15 patients, and observed no lead migration during either the screening period (average 38.8 days) or during follow-up of IPG implantation cases (average 11 months). The total infection rate in the whole series was 18/180 (10%), which was slightly higher than that reported by the sacral neuromodulation study group (6.1%). Revision rates for stage one and stage two were 12.2% and 20%, respectively. The revision rate in the original study group was 33.3%. Thus, with advancing technology, new problems may arise, but the implanting physician should be aware of the ways to evaluate and manage these complications and appropriately troubleshoot patients with suboptimal responses.

Algorithms↗
PubMed2004

Pelvic hematoma as a cause of bladder perforation and gross hematuria.

We present a case of an ulcerated perforation of the bladder caused by a large pelvic hematoma without any direct injury to the bladder in a 71-year-old woman. She developed the hematoma after emergency percutaneous angioplasty and placement of an intra-aortic balloon pump that was complicated by retroperitoneal bleeding from an injured femoral artery. She presented several days later with gross hematuria and right hydroureteronephrosis. Cystoscopy and cystography revealed an extraperitoneal perforation at the right bladder neck. Although conservative management was attempted, the patient eventually required open repair. The perforation had transformed to an intraperitoneal perforation by making a communicating tract through the absorbed hematoma. After debridement and excision of the tract, the bladder perforation was repaired in two layers.

Aged↗
PubMed2006

Complications and troubleshooting of two-stage sacral neuromodulation therapy: a single-institution experience.

OBJECTIVES: With the increasing use of sacral neuromodulation therapy, urologists are faced with postimplantation challenges. The purpose of this study was to identify these events and their causes and management in our large single-institution experience. METHODS: From July 2002 to September 2004, all patients who underwent sacral neuromodulation therapy for refractory bladder conditions were identified. Their medical records were retrospectively evaluated for history, operative intervention, and programming visits. Events after implantation of the implantable pulse generator (IPG) unit were noted. The evaluation, troubleshooting, management, and resolution of events at the last follow-up visit were extracted. RESULTS: A total of 214 patients underwent sacral neuromodulation therapy at our institution. The mean patient age was 53.5 +/- 15.4 years. Of the 214 patients, 161 underwent IPG implantation during a mean follow-up period of 16 months (range 5 to 30). The second-stage explantation and revision rate was 10.5% and 16.1%, respectively. The indications for explantation were infection (8 of 17) and failure to maintain a response (9 of 17). Revisions were done for decreases in response with abnormal (12 of 26) or normal (5 of 26) impedance measurements, IPG site discomfort (4 of 26), draining sinus at the IPG site (4 of 26), and lead migration (1 of 26). Equalization of impedance measurements was the most commonly observed impedance abnormality. These were managed by drying fluid from the connection in 4 patients and lead change in the rest. CONCLUSIONS: After IPG implantation, a decline in response may occur. Although some were explanted, most were revised, with most of the revisions functional on follow-up. Familiarity with impedance evaluation and development of algorithms for postimplant management are essential for troubleshooting and maintenance of the device.

Electric Stimulation Therapy↗
PubMed1979

Better postcoital test for oligospermic patients using split ejaculate artificial insemination.

In 25 oligospermic patients who had negative postcoital tests, artificial inseminations were performed with the whole semen and split ejaculates. After 30 minutes, a sample of cervical mucus was obtained and examined microscopically for the presence of motile spermatozoa. There was a significant improvement of 64% using the split ejaculate, as compared with 44% using whole semen. We found a significantly higher sperm count and progressive motility in the split ejaculate (18 patients, 72%).

Cell Count↗
PubMed1997

Observer variability in the diagnosis and management of the hysterosalpingogram.

OBJECTIVE: To determine the reproducibility of hysterosalpingogram (HSG) interpretation and clinical management recommendations among trained observers. DESIGN: Fifty HSG films were distributed to five fertility practitioners with a mean of 20 years clinical experience. Each observer evaluated components of uterine and tubal status and provided clinical recommendations for hysteroscopy and laparoscopy. SETTING: University hospital-affiliated reproductive endocrine practice. INTERVENTION(S): None MAIN OUTCOME MEASURE(s): The level of agreement among observers for each uterine and tubal category as determined by the kappa(kappa) statistic. Determinants of clinical recommendation for further diagnostic studies were assessed. RESULT(S): The level of agreement between observers as determined by kappa ranged from 0.645 in the hydrosalpinx category, indicating fair reliability, to 0.111 for pelvic adhesions, indicating poor reliability. The composite kappa for uterine status was 0.345 whereas the composite kappa for tubal status was 0.430. Agreement among observers concerning management showed marginal reproducibility with a kappa of 0.261. Overall, more than one abnormality of either the cavity or the fallopian tubes led to a diagnostic recommendation for further workup in > or = 90% of cases. CONCLUSION(S): In a group of five experienced clinicians, there was considerable variability in the interpretation as well as the clinical management of the HSG. Physicians caring for infertile couples should be aware of this discrepancy and should, if possible, review carefully both the original films as well as the report of the attending radiologist in formulating their diagnostic evaluation and management plan.

Adolescent↗
PubMed2004

Control of orienting movements: role of multiple tectal projections to the lower brainstem.

In movement neuroscience this past decade, a conceptual approach that puts emphasis on population coding was clearly dominant. The purpose of numerous studies has been to define presumably homogeneous groups of neurons on the basis of the correlation of their discharges with sensory and motor events. The goal of this chapter is to stress the importance of taking into account individual properties of neurons, this being an essential prerequisite for a biologically meaningful definition of neuron populations. Taking as an example the executive limb of the neural network controlling gaze movements, we demonstrate the functional and anatomical diversity of tectal and reticular neurons, which are generally considered as homogeneous populations and used, accordingly, as lumped elements in models. We argue that the extraction of effector-specific signals from the global command of gaze displacement is based not on the interplay between discrete neural modules, but rather on a gradual process of signal specification at all levels of the executive network. An eventual accurate description of this network will require knowledge of the unique combinations of afferent inputs and efferent connections for as many subsets of its constituent neurons as is conceivably possible.

Animals↗