A new Borrelia infecting Lone Star ticks.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
R D Smith
Publications and source records attributed to R D Smith.
Binding specificity of post-activated neocarzinostatin chromophore drug-bulged DNA complex studied using electrospray ionization mass spectrometry.
Electrospray ionization mass spectrometry (ESI-MS) was employed to characterize the binding specificity of a bulged 22-mer DNA hairpin with a post-activated neocarzinostatin chromophore (NCS-Chrom) having two similar forms, where 2a has an H in a location for which 2b has it replaced by a CH2OH group. Specific binding of 2a to the bulged 22-mer DNA was observed whereas little binding was detected for 2a to non-bulged DNA 19-mer and 12-mer duplexes. The stoichiometry of the 22-mer DNA complex with 2a was determined to be predominantly 1:1. Substitution of hydrogen in 2a for the hydroxymethylene group in 2b dramatically reduced the binding strength to the 22-mer DNA. Little complex formation was observed for 2b and 22-mer DNA based upon the ESI-MS data, consistent with earlier fluorescence studies. The results indicate that ESI-MS can be a sensitive technique for probing conformational specificity in studies of biomolecular binding.
Antibiotics, Antineoplastic↗
Specific metal-oligonucleotide binding studied by high resolution tandem mass spectrometry.
Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) was used to study the binding of metal ions to two oligonucleotides, d(pGCTTGCATp) and d(TTGGCCCTCCTT). Collision-induced dissociation (CID) of the metal-oligonucleotide complex revealed that metal ions preferentially bound to the central thymine region of the sequence. The most probable binding sites were the phosphodiester backbone since the sum of the maximum number of charge addition from the metal ions and the charge state of the whole complex was found to be equal to the number of ionizable protons on the DNA backbone. Although site-specific and sequence-specific binding was observed for all three of the metal ions studied, the binding specificity of UO2(2+) ions was significantly greater than for Mg2+ and Na+. These experiments demonstrate that ESI-MS/MS can be applied to study the binding of metal ions and their complexes to oligonucleotides, providing not only information on the number of metal ions binding to the oligonucleotide, but also information related to the binding site(s) and binding specificity.
Cyclotrons↗
Analysis of double-stranded polymerase chain reaction products from the Bacillus cereus group by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.
The analysis of polymerase chain reaction (PCR) products by electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR) has been achieved. Specifically, a 105 base-pair nucleotide portion of the ribosomal spacer region was amplified in two members of the B. cereus group (i.e. B. thuringiensis and B. cereus) using PCR. These amplified regions were then analyzed by gel electrophoresis and ESI-FTICR. Based on the predicted sequence of the PCR products for each organism, the mass measurement using ESI-FTICR matched the theoretical mass within experimental error and was consistent with gel electrophoresis results. In contrast, for the typical several hour time-scale of the gel electrophoresis experiment, the mass spectrometric analysis was completed in a matter of minutes. To our knowledge, this constitutes the first report demonstrating the ionization and detection of a double-stranded PCR product by ESI-MS. This preliminary result indicates the potential use of ESI-MS to analyze PCR products on a rapid time-scale, with potential for medical and taxonomic applications.
Bacillus cereus↗
Analysis of single cells with capillary electrophoresis electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.
Recent results with on-line capillary electrophoresis (CE) electrospray ionization (ESI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry suggest that CE/ESI-FTICR can provide a powerful technique for micro-sample analyses owing to the inherent sensitivity of the technique and the enhanced information content derived from high-performance mass measurements. Using micro-sampling methods and ion accumulation techniques based on quadrupolar excitation, we demonstrate that adequate sensitivity exists to characterize the hemoglobin from a single human erythrocyte (approximately 450 amol). In these studies mass spectra with average mass resolution in excess of 45 000 (FWHM) were obtained for both the alpha- and beta chain of hemoglobin following in-column lysing of a single erythrocyte.
Cyclotrons↗
The interface of capillary electrophoresis with high performance Fourier transform ion cyclotron resonance mass spectrometry for biomolecule characterization.
The interfacing of capillary electrophoresis (CE) with Fourier transform ion cyclotron resonance-mass spectrometry (FTICR-MS) and the factors which dictate obtainable performance (i.e., sensitivity, mass resolution, scan rate and duty cycle) are described. We demonstrate the current status of the technique with examples of capillary zone electrophoresis (CZE) and capillary isotachophoresis (CITP) with FTICR analyses of proteins and oligonucleotides, and describe current limitations on sensitivity and scan speed. The first on-line interfacing of capillary isoelectric focusing (CIEF) with FTICR is also demonstrated and shown to be effective for separating minor components of protein mixtures for on-line mass spectral analysis. Finally, the potential for greatly improved performance based upon recent advances in FTICR instrumentation and methods is briefly described.
Animals↗
Electrospray mass spectrometric investigation of the chaperone SecB.
Electrospray ionization mass spectrometry was used to investigate the structure of the Escherichia coli chaperone protein SecB. It was determined that the N-terminal methionine of SecB has been removed and that more than half of all SecB monomers are additionally modified, most likely by acetylation of the N-terminus or a lysine. The use of gentle mass spectrometer interface conditions showed that the predominant, oligomeric form of SecB is a tetramer that is stable over a range of solution pH conditions and mass spectrometer interface heating (i.e., inlet capillary temperatures). At very high pH, SecB dimers are observed. SecB contains a region that is hypersensitive to cleavage by proteinase K and is thought to be involved in conformational changes that are crucial to the function of SecB. We identified the primary site of cleavage to be between Leu 141 and Gln 142. Fourteen amino acids are removed, but the truncated form remains a tetramer with stability similar to that of the intact form.
Bacterial Proteins↗
Atypical (non-AT1, non-AT2) angiotensin receptors.
Explore the source record for details and available documents.
Angiotensin II↗
The effects of tropicamide on mydriasis in young rats exhibiting a natural deficit in passive-avoidance responding.
The young rat at post-natal day 18-22 exhibits a natural deficit in passive-avoidance responding that can be corrected with the acute systemic administration of different cholinomimetic drugs, such as tacrine. In order to evaluate the generality of this apparent cholinergic hypofunction, different doses of the anticholinergic agent tropicamide, were administered either systemically or dropped directly into the eye of young or adult rats. Tropicamide produced mydriasis in a dose-dependent manner. The ED50 for tropicamide dropped into the eye was 0.025% for adult rats and 0.12% for young rats. When doses between 0.3 and 100 mg/kg were delivered systemically, the mean time course for recovery to baseline pupil size was accelerated in young rats. The average time to recovery across all doses was 112 +/- 27 min (mean+/-SE) for young rats and 274 +/- 70 min for adults. When subcutaneous tacrine was given immediately to young rats after training in a passive-avoidance response (PAR) task, retention was enhanced at testing 24 hours later in a dose-dependent manner. The response latencies were statistically different from saline-treated controls at doses of 0.003 and 0.01 mg/kg. This was not observed in adult rats. Taken together these results suggest that the PAR, along with the mydriacyl response of the young rat to tropicamide, may be regulated by a system of subsensitive cholinergic receptors.
Aging↗
Use of the flare-up protocol with high dose human follicle stimulating hormone and human menopausal gonadotropins for in vitro fertilization in poor responders.
OBJECTIVE: To analyze the effect of high dose human FSH in combination with hMG with a flare-up leuprolide acetate (LA) protocol in patients undergoing IVF at risk for a poor response. DESIGN: Prospective. SETTING: Free-standing ambulatory IVF center. PATIENTS: Two hundred eighty-four patients underwent a LA screening test for IVF. Patients with a lack of flare response were considered at risk for a poor response and underwent ovarian stimulation with the flare-up LA protocol in combination with high dose human FSH and hMG. RESULTS: The poor responder group was compared with the good responders on the flare-up LA protocol and to patients undergoing ovulation induction with a luteal phase LA protocol. There were 53 poor responder flare-up LA cycles, 177 good responder flare-up LA cycles, and 54 luteal phase LA cycles. The cancellation rate was higher in poor flare-up LA responders (11.3 percent) compared with good flare-up LA responders (1.1 percent) and luteal phase LA cycles (1.8 percent). Peak E2 levels, number of oocytes, and number of embryos were significantly higher in the good flare-up LA responders. Fertilization rate was similar in all groups. Ongoing pregnancy rate per retrieval was 28 percent in good responders, 29 percent in poor responders, and 33 percent in luteal phase LA patients. Only one patient (0.4 percent) was hospitalized for severe ovarian hyperstimulation. CONCLUSION: The flare-up protocol with high-dose human FSH and hMG is a very good alternative for patients who are at high risk for a poor response. Although peak E2 and number of oocytes were significantly lower in this group, the patients who responded had the same fertilization and pregnancy rate as the good responders. Cancellation rate remains high in poor responders.
Adult↗
Laparoscopically assisted gamete intrafallopian transfer with local anesthesia and intravenous sedation.
OBJECTIVE: To determine the length of procedure, length of recovery, patient tolerance, complications, and pregnancy rate (PR) of laparoscopically assisted GIFT performed during local anesthesia with i.v. sedation. DESIGN: A retrospective study. SETTING: Freestanding private ambulatory surgical center. PATIENTS: Thirty-one consecutive couples with infertility. INTERVENTIONS: Laparoscopically assisted GIFT during local anesthesia with i.v. sedation. MAIN OUTCOME MEASURES: Surgery time, recovery time, patient tolerance, PR, miscarriage rate, and complications. RESULTS: Cannulation of at least one fallopian tube was achieved successfully in all patients. The average surgery time was 64 +/- 12 minutes (mean +/- SD). The average recovery time was 92 +/- 30 minutes. The PR was 39% with an ongoing PR of 32%. There were no intraoperative or postoperative complications. CONCLUSION: Local anesthesia with IV sedation for GIFT using a two-puncture laparoscopic technique was well tolerated by the patients. Our ongoing PR of 32% compares very favorably with other series using general anesthesia.
Adult↗
Capillary electrophoresis-mass spectrometry.
Explore the source record for details and available documents.
Animals↗
Is Regret Theory an alternative basis for estimating the value of healthcare interventions?
This paper presents an argument for the existence of "regret' influencing the valuation of alternative outcomes when making treatment decisions in healthcare. It is argued that valuation techniques as currently formulated rely upon the axioms of Expected Utility Theory (transitivity and independence). This potentially leads to a misrepresentation of the respondents true preferences over treatment alternatives, and thus results in the potential for "irrational' decisions being observed. A modified version of Regret Theory is outlined, and the results of a tentative empirical analysis provided to illustrate the importance of accounting for regret in the valuation of health states. It is concluded that regret is an important element in individual valuation and decision making in health care.
Colonic Neoplasms↗
Effect of ramipril on blood pressure and protein excretion rate in normotensive nondiabetic patients with proteinuria.
Angiotensin-converting enzyme inhibitors reduce proteinuria in both normotensive and hypertensive patients with proteinuric renal disease. However, the mechanism of the antiproteinuric effect has not been clarified. We performed a prospective, double-blind, placebo-controlled, randomized crossover trial to test the hypothesis that the antiproteinuric effect of ramipril was due to an improvement in glomerular permselectivity independent of blood pressure and glomerular filtration rate. The effect of low-dose (1.25 mg/d) and high-dose (5 mg/d) ramipril was assessed in 15 normotensive nondiabetic patients with proteinuria (> 150 mg/d). The study was divided into four 12-week periods: placebo, high- or low-dose ramipril, crossover to low- or high-dose ramipril, and placebo. Blood pressure, glomerular filtration rate, renal plasma flow rate, urinary protein excretion rate, and plasma angiotensin II levels were measured at the end of each period. Mean arterial pressure, urine protein to creatinine ratio, and albumin excretion rate decreased significantly during low- and high-dose ramipril. Glomerular filtration rate and renal plasma flow rate were not changed significantly. Plasma angiotensin II levels decreased with both low- and high-dose ramipril. There were no episodes of hypotension and only one subject developed cough during ramipril that did not require discontinuation of the study drug. In conclusion, administration of ramipril in both low and high doses lowered blood pressure and reduced proteinuria in this cohort of normotensive patients with a variety of proteinuric renal diseases. The antiproteinuric effect of ramipril is probably mediated by a reduction in glomerular capillary pressure.
Adolescent↗
Over-the-counter antimicrobials: the hidden costs of resistance.
Explore the source record for details and available documents.
Anti-Infective Agents↗
The effect of positive semen bacterial and Ureaplasma cultures on in-vitro fertilization success.
A total of 342 couples planning to undergo in-vitro fertilization (IVF) were examined for the presence of bacteria in semen prior to and during the procedure. Pregnancy rates were analysed retrospectively to ascertain any adverse affects if > 10000 colony forming units (CFU)/ml bacteria were detected in the semen sample. The most common bacteria isolated from semen were Enterococcus spp. (73%). The presence of these bacteria did not affect the pregnancy rate of the patients with positive cultures prior to (32%) or during (37%) the IVF procedure compared with those patients in whom no bacteria were detected (32%). Those patients with semen cultures positive for Escherichia coli prior to the IVF procedure, but which cleared after treatment had a higher pregnancy rate (60%) compared with those patients who were positive for E.coli at the time of the attempt. The group of patients with Staphylococcus aureus in the semen at the time of IVF also demonstrated a low pregnancy rate (17%). Of the patients. 36 (11%) had positive Ureaplasma cultures from the screening test carried out on the semen and 22% became pregnant after successful treatment. None of the three patients with persistently positive cultures became pregnant. In conclusion, the presence of Enterococcus in semen does not affect pregnancy rates following IVF. E.coli, S.aureus and Ureaplasma urealyticum may have a negative effect and should be treated.
Abortion, Spontaneous↗
Noncovalent interactions observed using electrospray ionization.
Explore the source record for details and available documents.
Mass Spectrometry↗
Impact of an orally administered insect growth regulator (lufenuron) on flea infestations of dogs in a controlled simulated home environment.
OBJECTIVE: To evaluate the ability of lufenuron to control cat flea (Ctenocephalides felis felis) populations on dogs under conditions simulating a naturally infested home environment. DESIGN: 2 treatment and 2 control groups of dogs. Treated dogs received lufenuron in tablet form monthly, and controls received excipient. Dogs had unrestricted access to indoor (carpeted) and outdoor (grassy) environments in which self-propagating flea populations had been established. ANIMALS: 17 adult female Beagles. PROCEDURE: Dogs were monitored for 77 days after initial infestation with fleas and 70 days after initial treatment. Efficacy of the drug was calculated on the basis of absolute reduction in flea counts and as a percentage of control. RESULTS: Lufenuron administration caused a statistically significant (P < 0.05) reduction in flea burdens in treated dogs, compared with controls. Initiation of treatment 7 days after infestation resulted in 75% control of F1-generation and 97% control of F2-generation fleas over a 70-day posttreatment period. CONCLUSIONS: Lufenuron was highly effective in reducing flea populations on dogs. The time required for control will vary with the duration (generation time) of the flea reproductive cycle and, hence, the geographic area in which the product will be used. The experimental results are most relevant to use of the product for control of an existing flea population in the Midwest.
Administration, Oral↗