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K S Smith

Publications and source records attributed to K S Smith.

At least 19 recordsLinked to original sources

A theory for the atmospheric energy spectrum: depth-limited temperature anomalies at the tropopause.

The horizontal spectra of atmospheric wind and temperature at the tropopause have a steep -3 slope at synoptic scales, but transition to -5/3 at wavelengths of the order of 500-1,000 km [Nastrom, G. D. & Gage, K. S. (1985) J. Atmos. Sci. 42, 950-960]. Here we demonstrate that a model that assumes zero potential vorticity and constant stratification N over a finite-depth H in the troposphere exhibits the same type of spectra. In this model, temperature perturbations generated at the planetary scale excite a direct cascade of energy with a slope of -3 at large scales, -5/3 at small scales, and a transition near horizontal wavenumber k(t) = f/NH, where f is the Coriolis parameter. Ballpark atmospheric estimates for N, f, and H give a transition wavenumber near that observed, and numerical simulations of the previously undescribed model verify the expected behavior. Despite its simplicity, the model is consistent with a number of perplexing features in the observations and demonstrates that a complete theory for mesoscale dynamics must take temperature advection at boundaries into account.

Journal Article↗

Utility of alkylaminoquinolinyl methanols as new antimalarial drugs.

Mefloquine has been one of the more valuable antimalarial drugs but has never reached its full clinical potential due to concerns about its neurologic side effects, its greater expense than that of other antimalarials, and the emergence of resistance. The commercial development of mefloquine superseded that of another quinolinyl methanol, WR030090, which was used as an experimental antimalarial drug by the U.S. Army in the 1970s. We evaluated a series of related 2-phenyl-substituted alkylaminoquinolinyl methanols (AAQMs) for their potential as mefloquine replacement drugs based on a series of appropriate in vitro and in vivo efficacy and toxicology screens and the theoretical cost of goods. Generally, the AAQMs were less neurotoxic and exhibited greater antimalarial potency, and they are potentially cheaper than mefloquine, but they showed poorer metabolic stability and pharmacokinetics and the potential for phototoxicity. These differences in physiochemical and biological properties are attributable to the "opening" of the piperidine ring of the 4-position side chain. Modification of the most promising compound, WR069878, by substitution of an appropriate N functionality at the 4 position, optimization of quinoline ring substituents at the 6 and 7 positions, and deconjugation of quinoline and phenyl ring systems is anticipated to yield a valuable new antimalarial drug.

3T3 Cells↗

Comparison of conventional testing to polymerase chain reaction in detection of Trichomonas vaginalis in indigenous women living in remote areas.

There are high rates of Trichomonas vaginalis in remote areas of Central Australia. Conventional tests for T. vaginalis have low sensitivity in this setting. Aims of the study were to estimate the prevalence of T. vaginalis, to assess the presence of clinical signs and symptoms, to compare a T. vaginalis polymerase chain reaction (PCR) test with conventional methods of diagnosis, and to compare the PCR from different samples, including self-collected swabs (SCS). Of 205 women recruited, the prevalence of T. vaginalis was 24%. The prevalence of T. vaginalis was higher in women under 25 years (33%), compared with those who were 25-34 years (26%) and those over 35 years (15%, P < 0.05). The sensitivity of T. vaginalis PCR detection from SCS (94%) was not statistically different from a practitioner-collected HVS (96%), but was superior to urine PCR (74%) and conventional methods. After multivariate analysis, those women with high pH were almost three times more likely to be positive for T. vaginalis (odds ratio = 2.71 with 95% confidence interval 1.06-6.93, P = 0.037). Superior assays such as PCR should be a diagnostic option to adequately screen and treat women with T. vaginalis, in order to reduce complications, including the increased risk of HIV transmission.

Adult↗

Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer's disease.

The purpose of this investigation was to use molecular and immunological techniques to determine whether oral Treponema infected the human brain. Pieces of frontal lobe cortex from 34 subjects were analyzed with species-specific PCR and monoclonal antibodies. PCR detected Treponema in 14/16 Alzheimer's disease (AD) and 4/18 non-AD donors (P < 0.001), and AD specimens had more Treponema species than controls (P < 0.001). PCR also detected Treponema in trigeminal ganglia from three AD and two control donors. Cortex from 15/16 AD subjects and 6/18 controls contained Treponema pectinovorum and/or Treponema socranskii species-specific antigens (P < 0.01). T. pectinovorum and/or T. socranskii antigens were also found in trigeminal ganglia and pons from four embalmed cadavers, and 2/4 cadavers also had Treponema in the hippocampus. These findings suggest that oral Treponema may infect the brain via branches of the trigeminal nerve.

Adult↗

Measurement of sitting balance using the Manchester Active Position Seat (MAPS): a feasibility study.

BACKGROUND: Evaluation of the effectiveness of therapy to improve sitting balance has been hampered by the limited number of sensitive objective clinical measures. We developed the Manchester Active Position Seat (MAPS) to provide a portable system to track change in the position of centre of force over time. OBJECTIVES: (1) To investigate whether there is correspondence between the measurement of position change by a forceplate and by MAPS. (2) To explore whether and how MAPS measures changes in position when seated healthy adults change posture. DESIGN: A feasibility study. METHODS: (1) An adult subject sat on MAPS placed on top of a forceplate. The x and y coordinates of the centre of pressure recorded from the forceplate and centre of force from MAPS during movement were compared graphically. (2) Four adults sat on MAPS using a standardized starting position and moving into six sets of six standardized target postures in a predetermined randomized order. The absolute shift in centre of force from the starting position was calculated. RESULTS: (1) The pattern of change of position over time was similar for the forceplate and for MAPS although there was a measurement difference, which increased with distance from the centre. (2) The direction of change of position corresponded to the direction of movement to the target postures but the amount of change varied between subjects. CONCLUSIONS: MAPS shows promise as an objective clinical measure of sitting balance, but peripheral accuracy of measurement needs to be improved.

Adult↗

The synthesis of amino-acid functionalized beta-carbolines as topoisomerase II inhibitors.

The synthesis and biological activity of amino acid functionalized beta-carboline derivatives, which are structurally related to azatoxin and the tryprostatins, are reported. These compounds were assayed for their growth inhibition properties in H520 and PC3 cell lines and were examined for their abilities to inhibit topoisomerase II-mediated DNA relaxation.

Amino Acids↗

Bone volume collected from dental implant sites during osteotomy.

PURPOSE: Little research has been done to determine the amount of bone harvested from implant site preparations using an inline bone collector. This study looked at the amount of bone that can be harvested from common dental implant osteotomies. PATIENTS AND METHODS: A total of 24 implants were placed in 9 patients over a 3-month period. Implant size ranged from 3.75 x 13 mm to 4.75 x 13 mm. Nine implants were placed in the maxilla, and 15 implants were placed in the mandible. Seven patients were female, and 2 patients were male. The patient age ranged from 27 to 72 years. Four patients had implants placed within 5 years after tooth extraction, and 5 patients had implants placed 5 years after tooth extraction: an analysis of variance was used to determine if there were statistical differences between maxilla versus mandible, male versus female, and edentulism less than or greater than 5 years. RESULTS: The average bone volume from the 24 osteotomies was 0.195 +/- 0.099 mL. The average osteotomy site measured 4.02 x 12.90 mm. There were no statistical differences noted among maxilla and mandible, gender, or time of edentulism. CONCLUSIONS: When using an inline bone collector to harvest implant osteotomy sites, an average of 0.195 mL of bone can be obtained from a site approximately 4.0 x 13 mm. This bone can often be combined with a xenograft or alloplastic material to provide extra bulk to fill peri-implant defects. When multiple implant sites are prepared, often sufficient bone can be obtained with the bone collector alone.

Adult↗

The use of a resorbable plating system for treatment of craniosynostosis.

PURPOSE: The purpose of this study was to evaluate the effectiveness of a resorbable plating system (Lactosorb; Walter Lorenz Surgical, Inc, Jacksonville, FL) as a fixation method in the treatment of craniosynostosis. PATIENTS AND METHODS: Ten children with 15 affected sutures underwent craniotomies ranging from release of 1 suture to total calvarial reconstruction. The 1.5 Lactosorb plating system was used as the method of fixation in all cases. Patients were evaluated clinically and with computed tomography scans before discharge postoperatively, and at the 3-, 6-, and 9-month intervals. RESULTS: In all 10 cases there was no evidence of neosynostosis, malposed osseous segments, or restriction of growth or calvarial expansion. In addition, none of the complications seen with more traditional techniques were evident in these patients. CONCLUSION: Resorbable plating systems provide a viable alternative to the more traditional fixation techniques that have been used to treat craniosynostosis and craniofacial dysostosis.

Absorbable Implants↗

Crystal structure of the "cab"-type beta class carbonic anhydrase from the archaeon Methanobacterium thermoautotrophicum.

The structure of the "cab"-type beta class carbonic anhydrase from the archaeon Methanobacterium thermoautotrophicum (Cab) has been determined to 2.1-A resolution using the multiwavelength anomalous diffraction phasing technique. Cab exists as a dimer with a subunit fold similar to that observed in "plant"-type beta class carbonic anhydrases. The active site zinc is coordinated by protein ligands Cys(32), His(87), and Cys(90), with the tetrahedral coordination completed by a water molecule. The major difference between plant- and cab-type beta class carbonic anhydrases is in the organization of the hydrophobic pocket. The structure reveals a Hepes buffer molecule bound 8 A away from the active site zinc, which suggests a possible proton transfer pathway from the active site to the solvent.

Amino Acid Sequence↗

Prokaryotic carbonic anhydrases.

Carbonic anhydrases catalyze the reversible hydration of CO(2) [CO(2)+H(2)Oright harpoon over left harpoon HCO(3)(-)+H(+)]. Since the discovery of this zinc (Zn) metalloenzyme in erythrocytes over 65 years ago, carbonic anhydrase has not only been found in virtually all mammalian tissues but is also abundant in plants and green unicellular algae. The enzyme is important to many eukaryotic physiological processes such as respiration, CO(2) transport and photosynthesis. Although ubiquitous in highly evolved organisms from the Eukarya domain, the enzyme has received scant attention in prokaryotes from the Bacteria and Archaea domains and has been purified from only five species since it was first identified in Neisseria sicca in 1963. Recent work has shown that carbonic anhydrase is widespread in metabolically diverse species from both the Archaea and Bacteria domains indicating that the enzyme has a more extensive and fundamental role in prokaryotic biology than previously recognized. A remarkable feature of carbonic anhydrase is the existence of three distinct classes (designated alpha, beta and gamma) that have no significant sequence identity and were invented independently. Thus, the carbonic anhydrase classes are excellent examples of convergent evolution of catalytic function. Genes encoding enzymes from all three classes have been identified in the prokaryotes with the beta and gamma classes predominating. All of the mammalian isozymes (including the 10 human isozymes) belong to the alpha class; however, only nine alpha class carbonic anhydrase genes have thus far been found in the Bacteria domain and none in the Archaea domain. The beta class is comprised of enzymes from the chloroplasts of both monocotyledonous and dicotyledonous plants as well as enzymes from phylogenetically diverse species from the Archaea and Bacteria domains. The only gamma class carbonic anhydrase that has thus far been isolated and characterized is from the methanoarchaeon Methanosarcina thermophila. Interestingly, many prokaryotes contain carbonic anhydrase genes from more than one class; some even contain genes from all three known classes. In addition, some prokaryotes contain multiple genes encoding carbonic anhydrases from the same class. The presence of multiple carbonic anhydrase genes within a species underscores the importance of this enzyme in prokaryotic physiology; however, the role(s) of this enzyme is still largely unknown. Even though most of the information known about the function(s) of carbonic anhydrase primarily relates to its role in cyanobacterial CO(2) fixation, the prokaryotic enzyme has also been shown to function in cyanate degradation and the survival of intracellular pathogens within their host. Investigations into prokaryotic carbonic anhydrase have already led to the identification of a new class (gamma) and future research will undoubtedly reveal novel functions for carbonic anhydrase in prokaryotes.

Amino Acid Sequence↗

Structural and kinetic characterization of an archaeal beta-class carbonic anhydrase.

The beta-class carbonic anhydrase from the archaeon Methanobacterium thermoautotrophicum (Cab) was structurally and kinetically characterized. Analytical ultracentrifugation experiments show that Cab is a tetramer. Circular dichroism studies of Cab and the Spinacia oleracea (spinach) beta-class carbonic anhydrase indicate that the secondary structure of the beta-class enzymes is predominantly alpha-helical, unlike that of the alpha- or gamma-class enzymes. Extended X-ray absorption fine structure results indicate the active zinc site of Cab is coordinated by two sulfur and two O/N ligands, with the possibility that one of the O/N ligands is derived from histidine and the other from water. Both the steady-state parameters k(cat) and k(cat)/K(m) for CO(2) hydration are pH dependent. The steady-state parameter k(cat) is buffer-dependent in a saturable manner at both pH 8.5 and 6.5, and the analysis suggested a ping-pong mechanism in which buffer is the second substrate. At saturating buffer conditions and pH 8.5, k(cat) is 2.1-fold higher in H(2)O than in D(2)O, consistent with an intramolecular proton transfer step being rate contributing. The steady-state parameter k(cat)/K(m) is not dependent on buffer, and no solvent hydrogen isotope effect was observed. The results suggest a zinc hydroxide mechanism for Cab. The overall results indicate that prokaryotic beta-class carbonic anhydrases have fundamental characteristics similar to the eukaryotic beta-class enzymes and firmly establish that the alpha-, beta-, and gamma-classes are convergently evolved enzymes that, although structurally distinct, are functionally equivalent.

Absorptiometry, Photon↗

Paediatric sleep apnoea and treatment with distraction osteogenesis.

Paediatric obstructive sleep apnoea (OSA) associated with craniofacial anomalies frequently is refractory to traditional treatment modalities. Skeletal expansion using distraction osteogenesis to correct facial deformities has proven to be an excellent treatment modality for the resolution of OSA. This paper discusses the use of distraction osteogenesis from infancy through adolescence and will show objective improvement in not only facial norms but also in OSA indices.

Adolescent↗

Carbonic anhydrase is an ancient enzyme widespread in prokaryotes.

Carbonic anhydrases catalyze the reversible hydration of CO(2) and are ubiquitous in highly evolved eukaryotes. The recent identification of a third class of carbonic anhydrase (gamma class) in a methanoarchaeon and our present finding that the beta class also extends into thermophilic species from the Archaea domain led us to initiate a systematic search for these enzymes in metabolically and phylogenetically diverse prokaryotes. Here we show that carbonic anhydrase is widespread in the Archaea and Bacteria domains, and is an ancient enzyme. The occurrence in chemolithoautotrophic species occupying deep branches of the universal phylogenetic tree suggests a role for this enzyme in the proposed autotrophic origin of life. The presence of the beta and gamma classes in metabolically diverse species spanning the Archaea and Bacteria domains demonstrates that carbonic anhydrases have a far more extensive and fundamental role in prokaryotic biology than previously recognized.

Archaea↗

Laparoscopic management of a unicornuate uterus with two cavitated, non-communicating rudimentary horns: case report.

An 18 year old nulligravid woman presented with severe dysmenorrhoea secondary to stage IV (revised American Fertility Society) endometriosis, right haematosalpinx, right endometrioma, unicornuate uterus and two cavitated, non-communicating rudimentary uterine horns. To our knowledge, this is the first reported case of a unicornuate uterus accompanied by two rudimentary horns. Operative video-laparoscopy proved a successful approach for treating this previously unreported variant of congenital Müllerian anomaly. A review of the world literature confirms the uniqueness of this case while demonstrating laparoscopy to be a viable alternative to laparotomy for management of congenital Müllerian anomalies. The case presented may help to elucidate Müllerian duct embryology further.

Adolescent↗

A plant-type (beta-class) carbonic anhydrase in the thermophilic methanoarchaeon Methanobacterium thermoautotrophicum.

Carbonic anhydrase, a zinc enzyme catalyzing the interconversion of carbon dioxide and bicarbonate, is nearly ubiquitous in the tissues of highly evolved eukaryotes. Here we report on the first known plant-type (beta-class) carbonic anhydrase in the archaea. The Methanobacterium thermoautotrophicum DeltaH cab gene was hyperexpressed in Escherichia coli, and the heterologously produced protein was purified 13-fold to apparent homogeneity. The enzyme, designated Cab, is thermostable at temperatures up to 75 degrees C. No esterase activity was detected with p-phenylacetate as the substrate. The enzyme is an apparent tetramer containing approximately one zinc per subunit, as determined by plasma emission spectroscopy. Cab has a CO(2) hydration activity with a k(cat) of 1.7 x 10(4) s(-1) and K(m) for CO(2) of 2.9 mM at pH 8.5 and 25 degrees C. Western blot analysis indicates that Cab (beta class) is expressed in M. thermoautotrophicum; moreover, a protein cross-reacting to antiserum raised against the gamma carbonic anhydrase from Methanosarcina thermophila was detected. These results show that beta-class carbonic anhydrases extend not only into the Archaea domain but also into the thermophilic prokaryotes.

Amino Acid Sequence↗

Phenotypic and genotypic heterogeneity among cultivable pathogen-related oral spirochetes and Treponema vincentii.

Recent findings challenge the assumption that pathogen-related oral spirochetes (PROS) are related to Treponema pallidum. Treponema vincentii, grown in OMIZ-Pat media, cross-reacted with monoclonal antibody H9-2 against T. pallidum, and cultivable PROS had 16S rRNA gene sequences similar to those of T. vincentii (C.-B. Choi, C. Wyss, and U. B. Göbel. J. Clin. Microbiol. 34:1922-1925, 1996). Aims of the present study were to determine whether antigen phenotypes of oral treponemas were influenced by growth conditions and to evaluate the genetic relatedness of cultivable PROS to T. pallidum and T. vincentii. Results show that three T. pallidum monoclonal antibodies (H9-1, H9-2, and F5) cross-reacted with whole cells from four Treponema species grown in modified OMIZ-Pat medium, but not with treponemas grown in NOS medium. Only H9-2 reacted in immunoblots with reduced proteins from cultivable PROS and T. vincentii. Three of five PROS isolates were amplified by T. vincentii-specific PCR, and one was amplified by Treponema medium-specific PCR. None were amplified by T. pallidum-specific PCR. Three of five PROS isolates had 16S ribosomal DNA restriction fragment length polymorphism patterns identical to that of T. vincentii, and the patterns of two isolates resembled that of T. medium. Arbitrarily primed-PCR profiles from whole genomic DNA were distinct among five PROS isolates and two T. vincentii strains. Thus, PROS isolates represent a heterogeneous group of treponemas that share some 16S rRNA gene sequences with T. vincentii and T. medium, but not with T. pallidum. It is proposed that the PROS nomenclature be dropped.

Antibodies, Monoclonal↗