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Biomedical subjects

A J Miller

Publications and source records attributed to A J Miller.

At least 37 records · Page 2Linked to original sources

Cold shock and its effect on ribosomes and thermal tolerance in Listeria monocytogenes.

Differential scanning calorimetry (DSC) and fatty acid analysis were used to determine how cold shocking reduces the thermal stability of Listeria monocytogenes. Additionally, antibiotics that can elicit production of cold or heat shock proteins were used to determine the effect of translation blockage on ribosome thermal stability. Fatty acid profiles showed no significant variations as a result of cold shock, indicating that changes in membrane fatty acids were not responsible for the cold shock-induced reduction in thermal tolerance. Following a 3-h cold shock from 37 to 0 degrees C, the maximum denaturation temperature of the 50S ribosomal subunit and 70S ribosomal particle peak was reduced from 73.4 +/- 0.1 degrees C (mean +/- standard deviation) to 72.1 +/- 0.5 degrees C (P < or = 0.05), indicating that cold shock induced instability in the associated ribosome structure. The maximum denaturation temperature of the 30S ribosomal subunit peak did not show a significant shift in temperature (from 67.5 +/- 0.4 degrees C to 66.8 +/- 0.5 degrees C) as a result of cold shock, suggesting that either 50S subunit or 70S particle sensitivity was responsible for the intact ribosome fragility. Antibiotics that elicited changes in maximum denaturation temperature in ribosomal components also elicited reductions in thermotolerance. Together, these data suggest that ribosomal changes resulting from cold shock may be responsible for the decrease in D value observed when L. monocytogenes is cold shocked.

Calorimetry, Differential Scanning↗

Murmurs associated with mitral annular calcification and aortic sclerosis.

BACKGROUND: Auscultation of patients with mitral annular calcification on echocardiography revealed a particular constellation of findings. OBJECTIVE: To test the hypothesis that a particular auscultatory constellation provides a high degree of certainty in diagnosing the combination of mitral annular calcification and aortic sclerosis so often found in the elderly. METHODS: Two groups of patients were studied to evaluate the particular auscultatory constellation under consideration which consisted of: (1) a harsh ejection systolic murmur heard from the 2nd right interspace to the cardiac apex and usually loudest between the 3rd left interspace and the apex; (2) the murmur radiates from the apex towards the left axilla and radiates poorly or not at all from the 2nd right interspace to the neck, and (3) the 2nd heart sound at the cardiac base is normal in intensity, and no ejection clicks are present. Group 1 consisted of patients with mitral annular calcification on echocardiographic examination, and group 2 consisted of patients in whom the particular constellation of auscultatory findings was present and who were then referred for echocardiographic assessment. RESULTS: The particular auscultatory constellation under investigation allowed the diagnosis of the presence of the combination of mitral annular calcification and aortic sclerosis with substantial accuracy. CONCLUSION: The findings in this exploratory study suggest that the pathologic combination of mitral annular calcification and aortic sclerosis can be diagnosed with a reasonably high degree of certainty in elderly patients, if the particular auscultatory configuration is identified.

Aged↗

A universally applicable clinical classification of lymphedema.

A simple classification of lymphedema is presented that is based solely on clinical observation. It is suggested that the universal use of such a classification would facilitate the collection of meaningful epidemiologic data and would make possible understandable comparisons of the effectiveness of various treatment modalities.

Epidemiologic Methods↗

Mandibulofacial adaptations in a juvenile animal model of temporomandibular joint arthritis.

Juvenile rheumatoid arthritis (JRA) is a chronic systemic disease of childhood that affects synovial joints including the temporomandibular joint (TMJ). Individuals with JRA of the TMJ frequently show aberrations in mandibulofacial development. Since the basis for these developmental perturbations is poorly understood, they remain a perplexing clinical problem to manage. To begin dissecting the mechanisms for altered craniofacial development in JRA of the TMJ, we characterized the gross morphologic adaptations in the facial skeleton in a juvenile animal model of TMJ arthritis. Arthritis was induced in ten 87-day-old male rabbits by intra-articular challenge with ovalbumin. Eight sham-challenged and 4 unchallenged rabbits were used as controls. Serial lateral head cephalograms, taken at 73 (T1), 87 (T2), 108 (T3), 129 (T4), and 150 (T5) days of age, were evaluated by linear measures of maxillary, mandibular, and posterior dental height dimensions. Differences in the absolute dimensions and relative percent incremental changes were compared by ANOVA and Fisher's test. The body weights, as well as the absolute measures and incremental changes in maxillary and posterior dental height dimensions, were not significantly different between the antigen-challenged and control groups. In contrast, absolute measures of posterior mandibular height, condylar neck height, and total mandibular length were significantly smaller (P < 0.05) in antigen-challenged rabbits than in both control groups at T5. Furthermore, the antigen-challenged rabbits demonstrated significantly smaller (P < 0.05) relative increases in all measures of mandibular length, and in total posterior mandibular and condylar neck heights. Cephalometric superimpositions on the cranial base and tantalum implants confirmed these quantitative observations. This investigation demonstrates mandibulofacial developmental aberrations in experimental JRA-like disease of the TMJ that are similar to those observed in humans with this disease.

Adaptation, Physiological↗

Failure of the canine principal ascending epicardial lymphatic to regenerate after transection.

We transected the principal ascending anterior epicardial cardiac lymphatic in 10 dogs, and after varying time intervals reoperated to look for lymphatic regeneration using dye injection. Photographs and sketches were made to record the findings, and in six dogs serial histologic sections were also examined. In none of the 10 dogs was regeneration of the transected principal cardiac lymphatic detected although small lymphatic collaterals from the distal side of the lymphatic developed in 2 dogs. Further studies are merited to assess the role of lymphatic insufficiency in the development of coronary vasculopathy and chronic rejection after cardiac transplantation and other heart operations (e.g., coronary artery bypass) that may injure lymphatic drainage capacity.

Animals↗

The morphology of the lymphatics of the coronary arteries in the dog.

On the supposition that pericoronary lymphatics play an important role in the efflux of interstitial fluid from the blood vessel wall, we examined the morphology of pericoronary arterial lymphatics in the dog. After ligation of the principal epicardial drainage lymphatics, after ligation of the left anterior descending coronary artery, after induced pericoronary inflammation and after instillation of India Ink into the pericardial sac using light, dissecting, and electron microscopy. The findings were compared with non-operated (control) dogs. Lymphatic drainage of the coronary arteries is via adventitial lymphatics, which do not penetrate to the media and via periadventitial lymphatics consisting of a subepicardial lymphatic plexus overlying the coronary arteries. The smaller arterioles in the ventricular muscle have many more accompanying lymphatics than do epicardial coronary arteries. In the latter arteries, prelymphatic channels formed by collagen fibers in the media likely transport interstitial fluid to the adventitial and periadventitial lymphatics. Arterial contraction also likely plays a role in propulsion of coronary arterial interstitial fluid towards adventitial lymphatics.

Animals↗

Cloning and functional characterization of a Brassica napus transporter that is able to transport nitrate and histidine.

A full-length cDNA for a membrane transporter was isolated from Brassica napus by its sequence homology to a previously cloned Arabidopsis low affinity nitrate transporter. The cDNA encodes a predicted protein of 589 amino acid residues with 12 putative transmembrane domains. The transporter belongs to a multigene family with members that have been identified in bacteria, fungi, plants, and animals and that are able to transport a range of different nitrogen-containing substrates, including amino acids, peptides, and nitrate. To identify the substrates of this plant gene, we have expressed the protein in Xenopus oocytes. The properties of the transporter are consistent with a proton cotransport mechanism for nitrate, and the voltage dependence of the Km for nitrate was determined. The Km for nitrate was shown to increase from 4 to 14 mM as the membrane voltage became more negative from -40 to -180 mV. Oocytes expressing the gene could accumulate internal nitrate to concentrations higher than those measured in water-injected controls. A range of different substrate molecules for the transporter was tested, but of these, histidine gave the largest currents, although the affinity was in the millimolar range. The pH dependence of the activity of the transporter was different for the substrates, with histidine transport favored at alkaline and nitrate at acid external pH. Kinetic analysis of the mechanism of histidine transport suggests a cotransport of protons and the neutral form of the amino acid, with the Km for histidine decreasing at more negative membrane voltages. This gene is the first member of this family of transporters for which the transport of two very different types of substrate, nitrate and histidine, has been demonstrated.

Animals↗

What is the threshold amount of starch necessary for full gravitropic sensitivity?

In preparation for microgravity experiments, we studied the kinetics of gravitropism in seedlings of wild-type (WT) Arabidopsis and three starch-deficient mutants. One of these mutants is starchless (ACG 21) while the other two are intermediate starch mutants (ACG 20 and ACG 27). In root cap cells, ACG 20 and 27 have 51% and 60% of the WT amount of starch, respectively. However, in endodermal cells of the hypocotyl, ACG 20 has a greater amount of starch than ACG 27. WT roots and hypocotyls were much more responsive to gravity than were the respective organs of the starchless mutant, and the intermediate starch mutants exhibited reduced gravitropism but had responses that were close to that of the WT. In roots, ACG 27 (more starch) was more responsive than ACG 20 (less starch), while in hypocotyls, ACG 20 (more starch) had a greater response than ACG 27 (less starch). Taken together, our data are consistent with the starch-statolith hypothesis for gravity perception in that the degree of graviresponsiveness is proportional to the total mass of plastids per cell. These results also suggest that (in roots) 51-60% starch is close to the threshold amount of starch needed for full gravitropism and that the gravity sensing system is "overbuilt."

Arabidopsis↗

Mechanisms and effects of transepithelial polarization in the isolated semicircular canal.

Previous studies have shown that galvanic stimulation of semicircular canal organs can modulate their afferent discharge. However, it has not been resolved whether this modulation derived from direct stimulation of hair cells, afferent nerve fibers, some combination of the two, or some as yet unknown path. This problem is addressed in the present study. Experiments were designed first to determine the gross current path necessary for the DC current to modulate afferent firing. These led to the conclusion that the current path had to flow between endolymph and perilymph across the neuroepithelium. Next, the various components in this established path were considered: the afferents, the hair cells, between the hair cells, or some combination of the three. These experiments led to the conclusion that the current pathway was across the hair cells causing transmitter release and thus affecting afferent activity.

Amiloride↗

Application and evaluation of male-specific bacteriophage as a process integrity or faecal contamination indicator in a pork slaughterhouse environment.

A male-specific bacteriophage plaque assay was evaluated as a faecal contamination or process integrity indicator for aspects of the pork slaughter process. Over 400 samples were tested including: sponge swabs from animal hauling trailer floors and dressed carcass surfaces; faecal material; water from slaughter sites; and water from each stage of wastewater treatment. Bacteriophage were observed in wastewater, trailers, slaughter process water and swine faeces. No bacteriophage were observed on dressed carcasses. Numbers of phage plaque-forming units per gram or millilitre showed greater variation and were usually lower than standard indicators, including total coliform or Escherichia coli counts. Among the applications studied, male-specific bacteriophage appear to be best suited for process control verification for wastewater treatment.

Abattoirs↗

Office-based anaesthesia.

Office-based anaesthesia is a young but rapidly growing speciality practice. In patient selection, surgical procedures, and anaesthetic techniques this practice is similar to standard ambulatory surgery; however, the liability and risks of office-based anaesthesia are greater. The anaesthesiologist's major challenge is to insist on patient safety in this developing field.

Journal Article↗

Gas tensions in cardiac lymph as a reflection of the interstitial space of the heart.

The purpose of this study was to determine the feasibility of measuring partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), and pH in cardiac lymph and to evaluate the relationship of these parameters to comparable measurements in arterial and coronary sinus blood in the normal heart under various respiratory conditions. In four anesthetized open-chest dogs, the principal cardiac lymphatic as well as the femoral artery and coronary sinus were cannulated. Ventilation was varied by changing oxygen concentration, tidal volume, and respiratory rate. PO2, pCO2, and pH were measured in the cardiac lymph, arterial blood, and coronary sinus blood after each change in ventilation. For pH and pCO2, good correlations were observed between the arterial blood and cardiac lymph, arterial blood and coronary sinus blood, and coronary sinus blood and cardiac lymph. The correlation between the pO2 measured in the arterial blood and the pO2 measured in the cardiac lymph was not as strong, and this may have been related to difficulty achieving a steady state. Gas tensions (pO2, pCO2, and pH) can be measured in cardiac lymph and may provide a window to the interstitial compartment of the heart. This is an additional tool for the laboratory study of ischemia and other forms of heart disease.

Animals↗

The lymphatic drainage of the left ventricle in the Yucatan minipig.

The gross anatomy of the cardiac lymphatic system draining the left ventricle was studied in 15 Yucatan minipigs and 2 regular swine. The findings confirm that the drainage pathways are similar to those of man and dog. After a coloring marker is injected near the apex of the left ventricle, one or more lymphatics are seen to ascend towards the left atrial appendage. Where there is more than one ascending lymphatic, they typically join before or at the left atrial appendage. This principal lymphatic then passes beneath the appendage and travels behind (dorsal to) the pulmonary artery and aorta to the right side of the mediastinum. From here, the lymphatic passes cephalad along the left border of the superior vena cava to enter the cardiac lymph node between the superior vena cava and the trachea.

Animals↗

A kinetic model with ordered cytoplasmic dissociation for SUC1, an Arabidopsis H+/sucrose cotransporter expressed in Xenopus oocytes.

To elucidate the kinetic properties of the Arabidopsis H+/sucrose cotransporter, SUC1, with respect to transmembrane voltage and ligand concentrations, the transport system was heterologously expressed in Xenopus laevis oocytes. Steady-state plasma membrane currents associated with transport of sucrose were measured with two-electrode voltage clamp over the voltage range -180 to +40 mV as a function of extracellular pH and sugar concentrations. At any given voltage, currents exhibited hyperbolic kinetics with respect to extracellular H+ and sugar concentrations, and this enabled determination of values for the maximum currents in the presence of each ligand (iHmax, iSmax for H+ and sucrose) and of the ligand concentrations eliciting half-maximal currents (KHm, KSm). The iHmax and iSmax exhibited marked and statistically significant increases as a function of increasingly negative membrane potential. However, the KHm and KSm decreased with increasingly negative membrane potential. Furthermore, at any given voltage, iSmax increased and KSm decreased as a function of the external H+ concentration. Eight six-state carrier models-which comprised the four possible permutations of intracellular and extracellular ligand binding order, each with charge translocation on the sugar-loaded or -unloaded forms of the carrier-were analyzed algebraically with respect to their competence to account for the ensemble of kinetic observations. Of these, two models (first-on, first-off and last-on, first-off with respect to sucrose binding as it passes from outside to inside the cell and with charge translocation on the loaded form of the carrier) exhibit sufficient kinetic flexibility to describe the observations. Combining these two, a single model emerges in which the binding on the external side can be random, but it can only be ordered on the inside, with the sugar dissociating before the proton.

Animals↗

A comparison of masticatory function in patients with or without reconstruction of the mandible.

BACKGROUND: The functional benefits of mandibular reconstruction following a composite resection remain unclear. Although microvascular surgical techniques have dramatically increased the predictability of bone and soft-tissue reconstruction towards presurgical anatomic norms, the specific factors responsible for improved function remain controversial. Objective measures of masticatory function need to be more clearly determined before the predictability and efficacy of reconstructive approaches is established. METHODS: We evaluated objective measures of oral function and patient reports of function in 10 reconstructed mandibulectomy patients, 10 without reconstruction, and 10 controls. Measures of oral function included bite force assessed at the first molar and incisal edge, a measure of tongue and cheek function, and patient reports of food they could eat. RESULTS: Both reconstructed and nonreconstructed patients presented decreased biting force, a more restricted diet, and compromised cheek and tongue function as compared with normals. However, reconstructed patients had significantly better measures of tongue function and ability to eat a varied diet than did nonreconstructed patients. Of the objective measures used to measure masticatory performance, bite force was poorly correlated, whereas measures of tongue function strongly correlated with successful mastication. CONCLUSION: Both reconstructed and nonreconstructed patients presented with a significant functional deficit when compared with normals, with reconstructed patients having better overall function than nonreconstructed patients.

Aged↗

Complete AV block following mediastinal radiation therapy: electrocardiographic and pathologic correlation and review of the world literature.

The clinical, features, serial electrocardiograms, and autopsy findings of a patient with symptomatic complete AV block, who had received mediastinal radiation therapy 8 1/2 years previously, are presented. The cardiac histopathology disclosed immense fibrosis of the conduction system and of the atria and ventricles. The enormous amount of fibrosis was similar in location and intensity to that observed in our previously reported patient (Cohen et al., Arch Intern Med 1981; 141:676-679) who had undergone mediastinal radiation. We conclude that the severe fibrosis was primarily due to radiation, rather than secondary to atherosclerotic coronary artery disease, which also has been described as a consequence of mediastinal radiotherapy. This patient's serial electrocardiograms disclosed evidence of complete block both in the AV nodal area and infra His system, which correlated well with the histopathology. The characteristic clinical features of patients with symptomatic complete AV block post mediastinal radiation therapy are presented, along with a review of the world literature.

Adult↗