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Biomedical subjects

A Drake

Publications and source records attributed to A Drake.

At least 19 recordsLinked to original sources
PubMed2005

Statins and fibrates for preventing melanoma.

BACKGROUND: Effective treatment for advanced melanoma is lacking. While no drug therapy currently exists for prevention of melanoma, in vitro, case-control, and animal model evidence suggest that lipid-lowering medications, commonly taken for high cholesterol, might prevent melanoma. OBJECTIVES: To assess the effects of statin or fibrate lipid-lowering medications on melanoma outcomes. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (February 2003), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (to March 2003), EMBASE (to September 2003), CANCERLIT (to October 2002), Web of Science (to May 2003), and reference lists of articles. We approached study investigators and pharmaceutical companies for additional information (published or unpublished studies). SELECTION CRITERIA: Trials involving random allocation of study participants, where experimental groups used statins or fibrates and participants were enrolled for at least four years of therapy. DATA COLLECTION AND ANALYSIS: Three authors screened 109 abstracts of articles with titles of possible relevance. We then thoroughly examined the full text of 72 potentially relevant articles. We requested unpublished melanoma outcomes data from the corresponding author of each qualifying trial. MAIN RESULTS: We identified 16 qualifying randomised controlled trials (RCTs) (seven statin, nine fibrate). Thirteen of these trials (involving 62,197 participants) provided data on incident melanomas (six statin, seven fibrate). A total of 66 melanomas were reported in groups receiving the experimental drug and 86 in groups receiving placebo or other control therapies. For statin trials this translated to an odds ratio of 0.90 (95% confidence interval 0.56 to 1.44) and for fibrate trials an odds ratio of 0.58 (95% confidence interval 0.19 to 1.82). Subgroup analyses failed to show statistically significant differences in melanoma outcomes by gender, melanoma occurrence after two years of participation in trial, stage or histology, or trial funding. Subgroup analysis by type of fibrate or statin also failed to show statistically significant differences, except for the statin subgroup analysis which showed reduced melanoma incidence for lovastatin, based on one trial only (odds ratio 0.52, 95% confidence interval 0.27 to 0.99). AUTHORS' CONCLUSIONS: The melanoma outcomes data collected in this review of RCTs of statins and fibrates does not exclude the possibility that these drugs prevent melanoma. There was a 10% and 42% reduction for participants on statins and fibrates, respectively, however these results were not statistically significant. Until further evidence is established, limiting exposure to ultraviolet radiation remains the most effective way to reduce the risk of melanoma.

Anticholesteremic Agents↗
PubMed2005

Variable assortative mating in replicate mating trials using Drosophila melanogaster populations derived from contrasting opposing slopes of 'Evolution Canyon', Israel.

Significant assortative mating in laboratory studies has been previously shown between two populations of Drosophila melanogaster collected from micro-climactically contrasting and opposing slopes of 'Evolution Canyon' (Lower Nahal Oren, Israel; Korol et al., 2000). Coupled with evidence that the two populations are adapted to their respective environments, this has been suggested as a rare example of ongoing behaviourally mediated speciation occurring in the face of gene flow. Reproductive isolation between these populations, however, has never been confirmed by replicate experiments in an independent laboratory. For this reason, we tested recent collections of these populations for premating isolation in both the original (Haifa) and a new (Burnaby) laboratory under a variety of experimental protocols. Although non-random mating was found in the majority of trials conducted in Haifa, we were unable to replicate these strong results in Burnaby. Most notably, we failed to detect assortative mating in four separate double choice experiments. Significant non-random mating was detected, however, in three of six single choice experiments in Burnaby, suggesting that the populations are behaviourally differentiated in some manner. Why nonrandom mating was weaker in Burnaby than Haifa is not understood, but suggests that assortative mating may be sensitive to unknown environmental factors.

Animals↗
PubMed2001

Use of rigid and flexible bronchoscopy among pediatric otolaryngologists.

OBJECTIVE: To explore how rigid and flexible bronchoscopy are used in pediatric otolaryngologic practice. DESIGN: Survey. PARTICIPANTS: Members of the American Society of Pediatric Otolaryngology who practice in the United States and Canada and were listed in the membership directory were eligible. Of the 206 members, 24 practicing outside the United States or Canada and 11 without an e-mail address or a fax machine were excluded. Hence, a questionnaire was e-mailed or faxed to 171 pediatric otolaryngologists. MAIN OUTCOME MEASURES: Questions concerned the practice setting, type and number of bronchoscopies, indications, complications, and medicolegal cases. RESULTS: Responses were received from 120 subjects (70.2%), with 3 retired and 2 practicing only otology, leaving 115 respondents who completed at least some of the questionnaire. Rigid and flexible bronchoscopy were performed by 72.7% (56/77) of those in academic settings and by 71.1% (27/38) of those in group or solo practices. In the last 12 months, approximately 10 454 total bronchoscopies were performed, with 2052 flexible and 9117 rigid bronchoscopies. Stridor, suspected foreign body inhalation, and laryngomalacia were the most common indications for bronchoscopy. Of the 83 respondents practicing rigid and flexible bronchoscopy, 25 (30.1%) used both instruments to manage complex or repeated foreign bodies, 25 (30.1%) used both to manage patients with cystic fibrosis, and 15 (18.1%) used both to manage simple foreign bodies. Complications were reported by 15.7% of the respondents, the most common being arrhythmia. Familiarity with a case resulting in medicolegal action was reported by 32.2% of the respondents. CONCLUSIONS: Rigid and flexible bronchoscopy have multiple uses in pediatric otolaryngologic practice. Also, flexible bronchoscopy appears to be emerging as a more frequently used diagnostic and therapeutic tool.

Bronchoscopes↗
PubMed1998

Effectiveness of patient delivered partner medication for preventing recurrent Chlamydia trachomatis.

OBJECTIVE: To determine if providing Chlamydia trachomatis infected women with medication to deliver to their sex partner(s) could reduce recurrent chlamydia infections compared with the standard partner referral method. STUDY DESIGN: A observational cohort study of 178 women, 14-39 years old attending a family planning clinic, diagnosed and treated for C trachomatis between October 1993 and December 1994 was conducted (43 received patient delivered partner medication (PDPM) and 135 received partner referral cards). Women were retested before or at their annual visit. RESULTS: The mean time of follow up was 17.7 months (SD 7.7). The PDPM group (n = 43) was similar to partner referral group (n = 135) for age, race, contraceptive method, history of an STD, and follow up time. The annual recurrent infection rate was lower among the PDPM group compared with the partner referral group (11.5% v 25.5%, p < 0.05). After adjusting for age in logistic regression, women in the PDPM group were less likely than women in the partner referral group to have an incident C trachomatis infection (OR 0.37, 95% CI 0.15-0.97, p < 0.05). CONCLUSION: These findings suggest that patient delivered partner medication can protect women from recurrent C trachomatis infection compared with the standard partner referral approach. Prospective studies with larger sample sizes are under way.

Adolescent↗
PubMed1998

Enantioselective biotransformation of aryl-isopropyl, -isopropenyl, and -propenyl groups by the rabbit or by the rat.

Thirteen kinds of aromatic compounds (Alkyl- and alkenyl-) were administered to rabbits and the chiralities of their optical active metabolite were determined by the synthesis of the enantiomers or their derivatives. This work has revealed many examples of enantioselective biotransformations and chiral inversion in the rabbits and mechanisms for this inversion have been proposed. The enantioselective hydration of transanethole epoxide was also examined in vitro in rat liver microsomes and possible mechanisms of this process are also discussed.

Animals↗
PubMed1997

Analysis of the architecture of the transcription factor sigma N (sigma 54) and its domains by circular dichroism.

Enhancer-dependent transcription in bacteria requires the alternative transcription factor sigma N (sigma 54), which forms an RNA polymerase holoenzyme that binds promoters as a transcriptionally inactive complex. We have examined the structure of sigma N by circular dichroism (CD) analysis. The sigma N protein and its domains are well structured in the absence of the core RNA polymerase subunits or promoter DNA. Denaturation of sigma N by temperature as followed by changes in CD shows a concomitant loss of secondary and tertiary structures with a melting temperature of 36 degrees C. The secondary structure displays a two-state melting curve with a second Tm of 85 degrees C. The amino-terminal Region I activation domain together with the acidic Region II does not contribute to the two-state melting. In marked contrast, the integrity of the C-terminal DNA-binding domain is required for the two-state melting. Measurements of pKb also demonstrated that a C-terminal part of sigma N, but not regions I or I + II, is required for the structural integrity of sigma N at high pH. Measurements of pKa suggested that alpha-helical structures are important in sigma N for the establishment of tertiary structural elements. The tertiary structure near ultraviolet CD signals of sigma N do not require regions I or I + II but were strongly diminished by C-terminal truncation of sigma N. Promoter DNA binding resulted in a conformational change in sigma N, permitting the determination of a binding constant. A typical B-DNA conformation was adopted by the promoter DNA. Implications for the modular domain organization of sigma N, the function of C-terminal sequences, and domain communication and its role in activation of transcription are discussed.

Base Sequence↗
PubMed1996

Purification and activities of the Rhodobacter capsulatus RpoN (sigma N) protein.

The rpoN-encoded sigma factors (sigma N) are a distinct class of bacterial sigma factors, with no obvious homology to the major sigma 70 class. The sigma N-containing RNA polymerase holoenzyme functions in enhancer-dependent transcription to allow expression of positively controlled genes. We have purified the Rhodobacter capsulatus sigma N protein, which is distinctive in lacking an acidic region implicated in the melting of promoter DNA by the Escherichia coll sigma N holoenzyme, and may represent a minor subclass of sigma N proteins. Assays of promoter recognition and holoenzyme formation and function showed that the purified R. capsulatus sigma N protein is distinct in activity compared to the enteric proteins, but retains the broad functions described for these proteins. As first described for the Klebsiella pneumoniae protein, promoter recognition in the absence of core RNA polymerase was detected, but contact of certain promoter bases by the R. capsulatus sigma N protein and its response to core RNA polymerase was clearly different from that determined for the K. pneumoniae and E. coli proteins. Results are discussed in the context of a requirement to modulate the activity of the DNA-binding surfaces of sigma N to regulate sigma N function. Circular dichroism was used to evaluate the structure of the R. capsulatus protein and revealed differences in the tertiary signals as compared to the K. pneumoniae protein, some of which are attributable to the DNA-binding domain of sigma N.

Amino Acid Sequence↗
PubMed1995

Imaging of nasopharyngeal atresia.

CT and MR revealed a case of nasopharyngeal atresia, a malformation in which the soft palate is not formed, and the hard palate extends posteriorly to fuse with the anterior surface of the clivus, resulting in complete isolation of the nasal and oral cavities and the absence of a nasopharynx. We believe this rare anomaly results from abnormal persistence of the embryologic bucconasal plate and/or anomalous migration of the nasoseptal elements.

Abnormalities, Multiple↗
PubMed1992

Identification of middle ear dysfunction in young children: a comparison of tympanometric screening procedures.

Two acoustic immittance screening procedures were evaluated in conjunction with pneumatic otoscopy, performed by a pediatric otolaryngologist. The subjects were 204 3- and 4-yr-old children from a rural area in eastern North Carolina. Pass-fail criteria were examined using two middle ear screening procedures: (1) a "traditional" procedure based on measures of tympanometric peak pressure and acoustic reflexes, and (2) the tympanometric measures contained within the American Speech-Language-Hearing Association's (ASHA) revised Guidelines for Screening for Hearing Impairment and Middle Ear Disorders. The traditional procedure resulted in low specificity but high sensitivity, whereas ASHA's immittance procedure resulted in high specificity but only moderate sensitivity. The negative predictive value was very high for both procedures; however, positive predictive value was low, especially for the traditional procedure. Advantages and disadvantages of the two procedures and future research needs are discussed.

Acoustic Impedance Tests↗
PubMed1991

Asymmetric synthesis of a precursor for the automated radiosynthesis of S-(3'-t-butylamino-2'-hydroxypropoxy)-benzimidazol-2-[11C]one (S-[11C]CGP 12177) as a preferred radioligand for beta-adrenergic receptors.

S-[1-(2,3-Diaminophenoxy)]-3'-(N-t-butylamino)propan-2'-ol has been synthesized in three steps from 2,3-dinitro-phenol and the chiral auxiliary, S-glycidyl-3-nitrobenzenesulphonate, to provide a precursor for labelling S-(3'-t-butylamino-2'-hydroxypropoxy)-benzimidazol-2-one (S-CGP 12177) with the short-lived positron-emitting radionuclide, carbon-11 (t 1/2 = 20.4 min; beta+ = 99.8%). Reaction of the diamine with [11C]phosgene, itself derived from no-carrier-added cyclotron-produced [11C]methane, provides radiochemically and chemically pure S-[carbonyl-11C]CGP 12177 in greater than 95% enantiomeric excess after HPLC. Automated apparatus is described for safely producing up to 5.9 GBq (160 mCi) of S-[11C]CGP 12177 with high sp. act. (20-40 GBq/mu mol or 0.54-1.08 Ci/mu mol) in a form suitable for human intravenous injection at only 30 min from the end of radionuclide production. S-[11C]CGP 12177 is preferred to the formerly described racemate as a radioligand for the study of beta-adrenergic receptors in vivo by positron emission tomography.

Adrenergic beta-Antagonists↗
PubMed1991

Pyrimidine nucleotide synthesis in the rat kidney in early diabetes.

Early renal hypertrophy of diabetes is associated with increases in the tissue content of RNA, DNA, and sugar nucleotides involved in the formation of carbohydrate-containing macromolecules. We have previously reported an increase in the activity of enzymes of the de novo and salvage pathways of purine synthesis in early diabetes; the present communication explores the changes in the pathways of pyrimidine synthesis. Measurements have been made of key enzymes of the de novo and salvage pathways at 3, 5, and 14 days after induction of diabetes with streptozotocin (STZ), phosphoribosyl pyrophosphate (PPRibP), and some purine and pyrimidine bases. Carbamoyl-phosphate synthetase II, the rate-limiting enzyme of the de novo route, did not increase in the first 5 days after STZ treatment, the period of most rapid renal growth; a significant rise was seen at 14 days (+38%). Dihydroorotate dehydrogenase, a mitochondrial enzyme, showed the most marked rise (+147%) at 14 days. The conversion of orotate to UMP, catalyzed by the enzymes of complex II, was increased at 3 days (+42%), a rise sustained to 14 days. The salvage route enzyme, uracil phosphoribosyltransferase (UPRTase), showed a pattern of change similar to complex II. The effect of the decreased concentration of PPRibP on the activities of CPSII, for which it is an allosteric activator, and on activities of OPRTase and UPRTase, for which it is an essential substrate, is discussed with respect to the relative Ka and Km values for PPRibP and the possibility of metabolite channeling.

Animals↗
PubMed1991

Surgical applications of ultrathin flexible bronchoscopes in infants.

Ultrathin flexible bronchoscopes with controlled distal angulation allow the conventional diagnostic examination of the lower airways of even the smallest infants. These instruments may be passed through small endotracheal or tracheostomy tubes while ventilation is maintained. It is thus possible, under direct visualization, to control the manipulation of surgical instruments where they could not otherwise be seen, or to study airway dynamics and anatomy intraoperatively without extubating the patient.

Airway Obstruction↗
PubMed1990

Conformational effects of nucleotide exchange in ras p21 proteins as studied by fluorescence spectroscopy.

The intrinsic fluorescence properties of the oncogene protein p21N-ras,p21H-ras and one of its transforming mutants, p21N-ras (Val12), have been investigated. A mutant containing a single tryptophan at position 28 in p21H-ras (Trp28) has been specifically engineered to provide a probe of protein conformation on nucleotide binding. The proteins produced essentially similar circular dichroism spectra typical of alpha/beta proteins. A decrease in the intensity of the fluorescence emission spectrum due to tyrosine occurred on GDP/GTP nucleotide exchange in the native and mutant proteins. Selective excitation of the single tryptophan in p21 produced a decrease in fluorescence intensity which was accompanied by a blue shift in the wavelength of maximum emission on nucleotide exchange. A reduction in the residual Mg2+ ion concentration enhanced this effect.

Circular Dichroism↗
PubMed1988

Circular dichroic spectra of elapid cardiotoxins.

Cardiotoxins isolated from elapid snake venoms constitute a chemically homogeneous family of molecules. Within this group several biologically different subclasses exist. We report a comparative analysis of the structure of 20 cardiotoxins using circular dichroism, immunological methods and secondary-structure prediction. It is shown that cardiotoxins fall within two structural subclasses. Toxins of group I are characterized by (a) CD spectra having an intense positive band close to 192.5 nm and a negative trough at 225 nm with no positive band around 230 nm, (b) strong cross-reactivity with a polyclonal antiserum specific for Naja nigricollis toxin gamma and (c) a high tendency to form a reverse turn in the region of position 11. Toxins of group II are characterized by (a) CD spectra displaying a much weaker positive band at 192.5 nm, a negative band around 210 nm and a positive band at 230 nm, (b) little cross-reactivity with the aforementioned antiserum and (c) a high reverse-turn potential at position 31. It is suggested that the observed differences result from differing curvatures in the antiparallel beta sheet which constitutes the main secondary structure of cardiotoxins.

Amino Acid Sequence↗