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Biomedical subjects

A J Miller

Publications and source records attributed to A J Miller.

At least 19 recordsLinked to original sources

The absence of lymphatics in normal and atherosclerotic coronary arteries in man: a morphologic study.

It has been suggested by various investigators that the impairment of lymphatic drainage from the coronary arteries may play a role in predisposition to coronary atherosclerosis, the pathogenesis of which is certainly multifactorial. In our study, no lymphatic vessels were found in the walls of the coronary arteries (adventitia, media and intima) in 51 human hearts from patients ranging in ages from 3 months to 83 years with normal coronary arteries, coronary atherosclerosis, and cardiomyopathy. Visualized lymphatics were located solely in the periadventitial area, and these lymphatics were more irregular in hearts from older persons. With injection, histology, and electronmicroscopy methods we could not detect penetration of lymphatics into the wall of coronary trunks in normal as well atherosclerotic arteries. In all coronary arteries studied, and particularly in the atherosclerotic lesions, blood vasa vasorum could be visualized. In the atherosclerotic areas, vasa vasorum (angiogenesis) could be seen penetrating into the media and intima. Many of the thin-walled vasa vasorum could easily be mistaken for lymphatics. The absence of lymphatics draining the epicardial coronary arteries may be a predisposing factor to coronary atherosclerosis.

Adolescent↗

Modeling of structure, quality, and function in the orthodontic patient.

The advantages of three-dimensional (3-D) imaging technology and solid modeling make it possible to visualize the morphological information. However, lacking in this 'digital patient' is the motion and mechanical properties observed in the living patient. Functional diagnostic techniques such as electromyography and motion analysis could complement the morphological characteristics to be applied in orthodontics. In this review, new computer-assisted analyzing methods are introduced which include visualization of: 1) the 3-D structure and bone density distribution; 2) masticatory-generated forces by using automated finite element modeling (FEM); and 3) the 3-D jaw movement and its motion analysis. In each study, the data from X-ray computed tomography scanning, electromyograms, biting pressure, and digital jaw movement analysis (six axes) are used for calculation. By using these applications, growing changes in bone mineral density distribution of the mandibular cortical bone have been clarified, automated finite element modeling has indicated stress distribution in the craniofacial skeleton, and patient-specific 3-D images of the mandible have been depicted as a motion picture. These studies were completed in 124 living subjects (75 females, 49 males) between 8 and 33 years of age. From these results, malfunctions during mastication were evaluated clearly with the individual patient craniofacial structures and its characteristics. These computer-based visualization techniques can be used to derive much clinically useful information, and to improve the combined evaluation of both static characteristics and dynamic function.

Adolescent↗

Computer-assisted simulations in orthodontic diagnosis and the application of a new cone beam X-ray computed tomography.

Computational simulations which include three-dimensional (3-D) image processing and biomechanical calculations should provide useful information to our research and orthodontic clinic as a clinical tool defined as 'thinking'. In this review, 1) biomechanical simulations applied to predict the mandibular growth; 2) mathematical models of virtual bone cells and 3) 3-D images and solid model simulations for surgical planning are introduced. In biomechanical simulation, biting force, electromyographic (EMG) activity and cephalograms of 32 subjects were applied. Computational results of mathematical model were compared with actual bone growth in a rat. Three-dimensional image and solid model of 14 patients were utilized for their treatment planning. From the results, several concepts of our simulations were confirmed: 1) reaction forces generated by masticatory muscles at the condyle control the direction of mandibular growth; 2) some mathematical models have the possibility to describe the process of bone growth; 3) 3-D image processing software and solid models are necessary for diagnosis and planning of orthognathic surgery. We also believe that the orthodontists can more accurately predict the affects of surgical procedures and orthodontic tooth movement using the new cone beam X-ray computed tomography (CT) (CB MercuRay; Hitachi Medico Technology, Tokyo, Japan) and its advanced application software.

Animals↗

Micro X-ray computed tomography analysis for the evaluation of asymmetrical condylar growth in the rat.

OBJECTIVES: To investigate the influence of forced lateral bite on mandibular growth, micro X-ray computed tomography (CT) was used for the purpose evaluating condylar cartilage and cancellous bone formation in 10 male Wister rats (3 weeks of age). SETTINGS AND SAMPLE POPULATION: The rats were divided into two groups--experimental and control. In experimental group, an inclined crown was cemented onto the maxillary incisors to produce 2.5 mm shift toward the left side during mastication. Right-left differences in whole mandibular length, mandibular height, condylar size, trabecular structure of the condylar head and three-dimensional (3-D) finite element analysis were assessed using 3-D images reconstructed from micro X-ray CT scans when the mice had reached 21 weeks. MEASUREMENTS AND RESULTS: Asymmetrical growth was found in the experimental group, in which the left condylar head became thicker and shorter than the right condylar head during development. When comparing the left and right condyles of the experimental animals, histomorphometric analysis from micro X-ray CT showed that the bone volume (BV) of the cancellous bone, the surface area of the cancellous bone (BS), the BS/BV ratio, the BV fraction (BV/TV), and the trabecular thickness and trabecular number were less for the right condyle than for the left condyle. CONCLUSIONS: These findings suggested that artificial changes in the mastication do influence the growth of condylar head, condylar bone trabecular structure, and mineralization.

Animals↗

Oral and pharyngeal reflexes in the mammalian nervous system: their diverse range in complexity and the pivotal role of the tongue.

The oral cavity and pharynx are anatomically separate but functionally integrated regions of the head. The two regions are involved in complex motor responses that include feeding, chewing, swallowing, speech, and respiration. The multiple sensory receptors that innervate these two regions provide the first link in reflexes that control muscles of the entire head, upper gastrointestinal tract, and airway. Most of the reflexes affect the diversity of muscles that compose the tongue, which is vital to all stages of feeding and which continually affects the patency of the airway. Oral-pharyngeal reflexes are evident in the mammalian fetus and continually emerge as the animal or human matures. Some of the first reflexes in the oral region are geared toward nourishment. As the central nervous system matures and the oral and pharyngeal regions develop morphologically, new reflexes develop. Many of these reflexes are protective both of the tissue in the oral cavity, such as the tongue, and of the upper airway in preventing aspiration. While simple reflexes can be evoked in isolation, most reflexes combine with more complex oral and pharyngeal responses such as chewing and vocalization. Oral-pharyngeal reflexes demonstrate a range in complexity. Some sensory stimuli will evoke a series of responses, as is often evident in the infant, and other stimuli will evoke a complex multiple-level recruitment of muscles in a sequence, as in pharyngeal swallowing. Certain sensory inputs evoke an entire motor behavior pattern, such as taste avoidance or facial expression. The oral-pharyngeal reflexes are critical to maintaining life and ultimately serve functions that the oral and pharyngeal regions have in common, such as communication, feeding, and breathing.

Animals↗

A three-dimensional, quantitative computed tomographic study of changes in distribution of bone mineralization in the developing human mandible.

The three-dimensional distribution of highly mineralized cortical bone on the buccal surface of the mandible was evaluated using quantitative computed tomography. The study was completed in 34 living persons (21 females and 13 males) between the ages of 9 and 32 yr of age with symmetrical mandibles. The geometrical distribution of the highly mineralized areas (>1250 mg/cm(3)) was determined by three-dimensional reconstruction of images. The pattern of distribution was evaluated by superimposing a 9 by 9-mesh grid over the lateral view of the mandible and adapting it to the same anatomical landmarks for different aged participants. Individuals demonstrated four different patterns of distribution of highly mineralized buccal cortical bone. The youngest had highly mineralized bone in the corpus of the mandible and along the anterior ramal border. In older individuals, the mineralization changed to include the mid- and posterior ramus. Highly mineralized bone was not found within the condylar, coronoid, or gonial angle regions of any participant. A comparison of the mineralization pattern between the left and right lateral mandibular views showed bilateral symmetry with similar patterns of distribution. Comparison of the number of grids occupied by highly mineralized cortical bone with the age of the participant, mandibular length, gonial angle, and cross-sectional area of the masseter muscle produced the highest correlation coefficient with the size of the masseter muscle.

Adolescent↗

Cortical bone mineral density in asymmetrical mandibles: a three-dimensional quantitative computed tomography study.

The three-dimensional distribution (3D) of the highest mineralized cortical bone was evaluated in 32 subjects between the ages of 8 and 30 years with asymmetrical mandibles using quantitative computed tomography (QCT). The geometrical distribution of the highest mineralized areas (> 1250 mg/cm3) representative of mandibular cortical bone was determined by 3D reconstruction of the images. The length of the mandible on each side was determined by defining a new linear measurement from the centre of the 3D reconstructed condyle to the midline of the symphysis as identified from a submental view. The cross-sectional areas of the masseter and medial pterygoid muscles were assessed from bilateral axial views through the middle of the muscles parallel to the Frankfort-Horizontal plane. Comparison between the lengths of the two mandibular sides (right-left = mm) indicated a range of asymmetries with an equal number of subjects with the left and right mandible longer. Comparison of the area of highest mineralized cortical bone between the right and left sides (R/L) to the ratio of the mandibular length (R/L) showed a high correlation coefficient (r = 0.629) suggesting that the shortest mandibular side had more highly mineralized bone. A comparison of the area of highest mineralized cortical bone between the right and left sides (R/L) to the ratio of cross-sectional areas of the muscles showed the highest correlation coefficient (r = 0.724) with the ipsilateral masseter muscle. These findings indicate that asymmetrical mandibles are associated with asymmetrical distributions of the highest mineralized cortical bone and that this is age dependent.

Adolescent↗

A randomized, double-blind comparison of the efficacy and tolerability of once-daily modified-release diltiazem capsules with once-daily amlodipine tablets in patients with stable angina.

A randomized, double-blind, parallel-group study comparing the efficacy and tolerability of once-daily diltiazem capsules with amlodipine tablets in patients with stable angina. After a run-in period of 1 to 3 weeks, 34 patients received once-daily diltiazem and 33 patients received amlodipine. Patients received either diltiazem, 240 mg/day, or amlodipine, 5 mg/day, for 2 weeks followed by diltiazem, 360 mg/day, or amlodipine, 10 mg/day, for 2 weeks. Standard treadmill exercise testing was the primary efficacy assessment. Patients also recorded incidence of angina attacks and use of glyceryl trinitrate spray. Both treatments gave significant improvement in time to onset of angina and time to maximal exercise. With the exception of amlodipine, 5 mg/day, both treatments gave significant increases in time to 1-mm ST segment depression. Diltiazem, 360 mg/day, gave a significant decrease in rate pressure product. There were no significant treatment differences in any of the exercise test parameters. Both treatments reduced incidence of angina attacks and use of glyceryl trinitrate spray. The incidence of edema was significantly less in patients receiving diltiazem. In conclusion, both treatments were effective in controlling patients' angina, but diltiazem was better tolerated, with a lower incidence of edema.

Adult↗

(+/-)-1-Tetralone-3-carboxylic acid and (+/-)-1-tetralone-2-acetic acid: hydrogen bonding in two gamma-keto acids.

The crystal structure of (+/-)-4-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (C(11)H(10)O(3)) involves projection of the carboxyl group nearly orthogonal to the aromatic plane and hydrogen bonding of the acid groups by centrosymmetric pairing across the a edge and the center of the chosen cell [O...O = 2.705 (2) A]. Intermolecular C--H...O==C close contacts to translationally related molecules are found for both the ketone (2.55 A) and the acid (2.67 A). In (+/-)-1-oxo-1,2,3,4-tetrahydronaphthalene-2-acetic acid (C(12)H(12)O(3)), the aggregation involves centrosymmetric carboxyl dimers mutually hydrogen bonded across the bc face and the a edge of the chosen cell [O...O = 2.674 (2) A]. A 2.60 A close C--H...O==C contact is found to the carboxyl group of centrosymmetrically related molecule.

Journal Article↗

The use of microelectrodes to investigate compartmentation and the transport of metabolized inorganic ions in plants.

Microelectrode measurements can be used to investigate both the intracellular pools of ions and membrane transport processes of single living cells. Microelectrodes can report these processes in the surface layers of root and leaf cells of intact plants. By careful manipulation of the plant, a minimum of disruption is produced and therefore the information obtained from these measurements most probably represents the 'in vivo' situation. Microelectrodes can be used to assay for the activity of particular transport systems in the plasma membrane of cells. Compartmental concentrations of inorganic metabolite ions have been measured by several different methods and the results obtained for the cytosol are compared. Ion-selective microelectrodes have been used to measure the activities of ions in the apoplast, cytosol and vacuole of single cells. New sensors for these microelectrodes are being produced which offer lower detection limits and the opportunity to measure other previously unmeasured ions. Measurements can be used to determine the intracellular steady-state activities or report the response of cells to environmental changes.

Biological Transport, Active↗

An improved Na+-selective microelectrode for intracellular measurements in plant cells.

The high background K+ concentration in plant cells is a problem for intracellular measurements of Na+ using ion-selective microelectrodes. The discrimination between Na+ and K+ of the microelectrode ionophore molecule limits the usefulness of this technique. A new Na+-selective microelectrode with an ionophore incorporating a tetramethoxyethyl ester derivative of p-t-butyl calix[4]arene has been developed. Microelectrodes made with this new sensor have superior selectivity for Na+ over K+ resulting in a lower limit of detection when compared with microelectrodes made using a commercially available ionophore (ETH227). Both types of microelectrodes were insensitive to changes in ionic strength and physiological ranges of pH, but only the calixarene-based electrodes showed no protein interference. To test the suitability of the calixarene-based microelectrodes for measurements in plants, they were used to measure Na+ in epidermal cells in the zone 10-20 mm from the root apex of barley (Hordeum vulgare L.). Seedlings were grown in a nutrient solution containing 200 mM NaCl for 1-6 d. The range of intracellular Na+ activity (a(Na)) measured varied from < or =0.1 mM (limit of detection) to over 100 mM, and these values increased significantly with time. The membrane potential (E(m)) of these cells was variable, but the values became significantly more negative with time, although there was no significant correlation between E(m) and a(Na). These intracellular measurements could not be separated into distinct populations that might be representative of subcellular compartments.

Acetamides↗

Lymphatic drainage of the heart in the laboratory rat.

We showed in the Sprague Dawley rat that the principal ascending cardiac lymphatic is similar in location to that of man and dog and can be readily visualized by injection of a small amount of T1824 blue dye (Evans) into the apex of the left ventricle. We also showed that it is possible to ligate and thereby obstruct this principal cardiac lymphatic near its entry beneath the left atrial appendage. This latter technique may be useful for studying in a small relatively inexpensive laboratory animal the effects of blocking cardiac lymph drainage on inflammatory and infectious processes implicated in myocardial and coronary artery disease.

Animals↗

A high affinity fungal nitrate carrier with two transport mechanisms.

We have expressed the CRNA high affinity nitrate transporter from Emericella (Aspergillus) nidulans in Xenopus oocytes and used electrophysiology to study its properties. This method was used because there are no convenient radiolabeled substrates for the transporter. Oocytes injected with crnA mRNA showed nitrate-, nitrite-, and chlorite-dependent currents. Although the gene was originally identified by chlorate selection there was no evidence for transport of this anion. The gene selection is explained by the high affinity of the transporter for chlorite, and the fact that this ion contaminates solutions of chlorate. The pH-dependence of the anion-elicited currents was consistent with H(+)-coupled mechanism of transport. At any given voltage, currents showed hyperbolic kinetics with respect to extracellular H(+), and these data could be fitted with a Michaelis-Menten relationship. But this equation did not adequately describe transport of the anion substrates. At higher concentrations of the anion substrates and more negative membrane voltages, the currents were decreased, but this effect was independent of changes in external pH. These more complicated kinetics could be fit by an equation containing two Michaelis-Menten terms. The substrate inhibition of the currents could be explained by a transport reaction cycle that included two routes for the transfer of nitrate across the membrane, one on the empty carrier and the other proton coupled. The model predicts that the substrate inhibition of transporter current depends on the cytosolic nitrate concentration. This is the first time a high affinity nitrate transport activity has been characterized in a heterologous system and the measurements show how the properties of the CRNA transporter are modified by changes in the membrane potential, external pH, and nitrate concentration. The physiological significance of these observations is discussed.

Animals↗

Xenopus oocytes as an expression system for plant transporters.

The Xenopus oocyte provides a powerful system for the expression and characterisation of plant membrane proteins. Many different types of plant membrane proteins have been expressed and characterised using this system. As there are already several general reviews on the methodology for oocyte expression of channel proteins, we have summarised the particular advantages and disadvantages of using the system for the characterisation of plant cotransporter proteins. As an example of how the system can be used to identify transporters, we describe evidence for a low affinity nitrate transporter in oocytes injected with poly(A) RNA extracted from nitrate-induced barley roots. Furthermore, we describe evidence that the expression of some transporters in oocytes can modify the properties of endogenous membrane proteins. We conclude that although care must be taken in the interpretation of results and in choosing appropriate controls for experiments, oocyte expression is an excellent tool which will have an important role in characterising plant membrane proteins.

Animals↗

A high affinity nitrate transport system from Chlamydomonas requires two gene products.

A nitrate-regulated cluster of genes involved in nitrate transport and assimilation has been identified in Chlamydomonas reinhardtii. Mutant strains of the alga, which are defective in some aspect of transport and assimilation have been used to assign functions to these genes. This analysis has suggested that two gene products are necessary to obtain a functional high affinity nitrate system in Chlamydomonas [Quesada et al. (1994) Plant J. 5, 407-419]. In this paper we have tested this hypothesis by injecting Xenopus oocytes with mRNA prepared from these two cDNAs, Nrt2;1 and Nar2, and then assaying the oocytes for nitrate transport activity. Oocytes injected with single types of mRNA did not show any nitrate transport activity. Furthermore, Nar2 mRNA was toxic to oocytes, with nearly 60%, of the oocytes dead 3 days after the injection. However, when oocytes were injected with a mixture of two mRNAs prepared from Nrt2;1 and Nar2, a high affinity nitrate transport activity could be measured. However, the Km for nitrate of this transport system was 28 microM which is higher than the value of 1.6 microM which had been obtained by the analysis of mutant phenotypes. The pH-dependence of the nitrate-elicited currents was consistent with a proton-cotransport mechanism. These results prove that two gene products are required to produce a functional high affinity nitrate transport system and that this process does not involve transcriptional regulation.

Animals↗

Determination of mosquito bloodmeal pH in situ by ion-selective microelectrode measurement: implications for the regulation of malarial gametogenesis.

Malarial gametocytes circulate in the peripheral blood of the vertebrate host as developmentally arrested intra-erythrocytic cells, which only resume development into gametes when ingested into the bloodmeal of the female mosquito vector. The ensuing development encompasses sexual reproduction and mediates parasite transmission to the insect. In vitro the induction of gametogenesis requires a drop in temperature and either a pH increase from physiological blood pH (ca pH 7.4) to about pH 8.0, or the presence of a gametocyte-activating factor recently identified as xanthurenic acid (XA). However, it is unclear whether either the pH increase or XA act as natural triggers in the mosquito bloodmeal. We here use pH-sensitive microelectrodes to determine bloodmeal pH in intact mosquitoes. Measurements taken in the first 30 min after ingestion, when malarial gametogenesis is induced in vivo, revealed small pH increases from 7.40 (mouse blood) to 7.52 in Aedes aegypti and to 7.58 in Anophĕles stephensi. However, bloodmeal pH was clearly suboptimal if compared to values required to induce gametogenesis in vitro. Xanthurenic acid is shown to extend the pH-range of exflagellation in vitro in a dose-dependent manner to values that we have observed in the bloodmeal, suggesting that in vivo malarial gametogenesis could be further regulated by both these factors.

Aedes↗

Improved efficacy and safety of controlled-release diltiazem compared to nifedipine may be related to its negative chronotropic effect.

The objective of this study was to assess the safety and efficacy of long-acting preparations of two commonly used calcium antagonists with particular reference to their effects on heart rate. Twenty patients with chronic stable angina were recruited to a double-blind, double-dummy crossover study of controlled-release diltiazem (diltiazem CR) versus sustained-release nifedipine (nifedipine SR) and underwent clinical assessment, symptom and adverse event reporting, and repeated treadmill exercise tests over a 10- to 11-week period. The main outcome measures were heart rate at rest and exercise, incidence of angina and nitroglycerin use, treadmill exercise performance (duration, time to angina, time to 1-mm ST-segment depression, heart rate at equivalent maximal exercise, and maximal ST-segment depression), and adverse events. Diltiazem CR significantly reduced heart rate at rest and equivalent exercise and incidence of angina and nitroglycerin use compared with nifedipine SR. Exercise duration time to angina and time to 1-mm ST-segment depression (but not maximal ST-segment depression) were all significantly improved by diltiazem CR. Diltiazem CR also caused significantly fewer adverse events than nifedipine SR. Calcium antagonists with negative chronotropic effects (eg, diltiazem CR) are safer and more efficacious as monotherapy in chronic stable angina than dihydropyridines (eg, nifedipine SR) even when a long-acting formulation of the latter is used.

Adult↗

Cold shock induction of thermal sensitivity in Listeria monocytogenes.

Cold shock at 0 to 15 degrees C for 1 to 3 h increased the thermal sensitivity of Listeria monocytogenes. In a model broth system, thermal death time at 60 degrees C was reduced by up to 45% after L. monocytogenes Scott A was cold shocked for 3 h. The duration of the cold shock affected thermal tolerance more than did the magnitude of the temperature downshift. The Z values were 8.8 degrees C for controls and 7.7 degrees C for cold-shocked cells. The D values of cold-shocked cells did not return to control levels after incubation for 3 h at 28 degrees C followed by heating at 60 degrees C. Nine L. monocytogenes strains that were cold shocked for 3 h exhibited D(60) values that were reduced by 13 to 37%. The D-value reduction was greatest in cold-shocked stationary-phase cells compared to cells from cultures in either the lag or exponential phases of growth. In addition, cold-shocked cells were more likely to be inactivated by a given heat treatment than nonshocked cells, which were more likely to experience sublethal injury. The D values of chloramphenicol-treated control cells and chloramphenicol-treated cold-shocked cells were no different from those of untreated cold-shocked cells, suggesting that cold shock suppresses synthesis of proteins responsible for heat protection. In related experiments, the D values of L. monocytogenes Scott A were decreased 25% on frankfurter skins and 15% in ultra-high temperature milk if the inoculated products were first cold shocked. Induction of increased thermal sensitivity in L. monocytogenes by thermal flux shows potential to become a practical and efficacious preventative control method.

Animals↗