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Biomedical subjects

J M Miller

Publications and source records attributed to J M Miller.

At least 199 records · Page 11Linked to original sources
PubMed1997

Spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus) and Rocky Mountain elk (Cervus elaphus nelsoni) in northcentral Colorado.

Between March 1981 and June 1995, a neurological disease characterized histologically by spongiform encephalopathy was diagnosed in 49 free-ranging cervids from northcentral Colorado (USA). Mule deer (Odocoileus hemionus) were the primary species affected and accounted for 41 (84%) of the 49 cases, but six Rocky Mountain elk (Cervus elaphus nelsoni) and two white-tailed deer (Odocoileus virginianus) were also affected. Clinical signs included emaciation, excessive salivation, behavioral changes, ataxia, and weakness. Emaciation with total loss of subcutaneous and abdominal adipose tissue and serous atrophy of remaining fat depots were the only consistent gross findings. Spongiform encephalopathy characterized by microcavitation of gray matter, intraneuronal vacuolation and neuronal degeneration was observed microscopically in all cases. Scrapie-associated prion protein or an antigenically indistinguishable protein was demonstrated in brains from 26 affected animals, 10 using an immunohistochemical staining procedure, nine using electron microscopy, and seven using Western blot. Clinical signs, gross and microscopic lesions and ancillary test findings in affected deer and elk were indistinguishable from those reported in chronic wasting disease of captive cervids. Prevalence estimates, transmissibility, host range, distribution, origins, and management implications of spongiform encephalopathy in free-ranging deer and elk remain undetermined.

Adipose Tissue↗
PubMed1997

Location and stability of rectus muscle pulleys. Muscle paths as a function of gaze.

PURPOSE: The paths of the rectus extraocular muscles (EOMs) are constrained by pulleys, connective tissue sleeves mechanically coupled to the orbital walls. This study sought to investigate, using high-resolution magnetic resonance imaging (MRI), the location and stability of EOM pulleys in normal subjects and those with strabismus. METHODS: Multiple contiguous coronal MRI scans spanning the anterior-to-posterior extent of the orbit during primary gaze, upgaze, downgaze, adduction, and abduction were analyzed digitally to determine the paths of the rectus EOMs. Pulley locations were inferred from EOM paths. RESULTS: Data for 10 orbits of six normal subjects established the normal paths of the rectus extraocular muscles in primary gaze. Muscle paths in primary position were highly uniform across normal subjects. In secondary gaze positions, rectus muscle paths at the level of the pulleys exhibited small but consistent shifts, relative to the orbit, opposite the direction of gaze, consistent with the expected mechanical effects of the intermuscular connective tissue suspensions of the pulleys. Twelve orbits of seven subjects with strabismus showed, as a group, no significant difference from normal in rectus muscle paths in primary gaze and no significant difference from normal in changes of muscle paths in secondary gaze. Two subjects with incomitant strabismus wer found to have grossly abnormal rectus muscle paths in primary gaze, suggesting heterotopic pulleys. Computer simulations of these heterotopic pulley locations accounted for the observed patterns of incomitant strabismus in both. CONCLUSIONS: High-resolution MRI can determine the location and sideslip of rectus EOM pulleys. Pulley position is highly uniform across normal subjects, consistent with the notion that musculo-orbital tissue connections determine the pulling direction of the rectus EOMs. In normal subjects and subjects with strabismus, pulleys exhibit small shifts with eccentric gaze that are consistent with secondary intermuscular, but not musculo-global, mechanical couplings. Heterotopic pulley position is a potential cause of incomitant strabismus.

Adult↗
PubMed1997

Meeting the challenge of emerging pathogens: the role of the United States Air Force in global influenza surveillance.

Influenza virus is one of the most ubiquitous organisms on the planet, causing illness in much of the population each year. The dynamic nature of the influenza virus requires similarly dynamic surveillance and prevention initiatives. The efforts of national surveillance programs, overseen by the World Health Organization and administered by institutions such as the U.S. Centers for Disease Control and Prevention, the U.S. armed forces, and 60 to 70 collaborating laboratories, annually culminate in the development of effective influenza vaccines. The U.S. Air Force's contribution is via Project Gargle, through which bases in various locations worldwide conduct active surveillance and submit throat swab specimens for virus isolation and characterization; the results of these laboratory analyses help determine the composition of the following year's influenza vaccine. These collaborative efforts have resulted in an identical or close antigenic match between vaccine and epidemic strains in 8 of the last 9 influenza seasons.

Centers for Disease Control and Prevention, U.S.↗
PubMed1997

A comparison of intraoral antimicrobial effects of stabilized stannous fluoride dentifrice, baking soda/peroxide dentifrice, conventional NaF dentifrice and essential oil mouthrinse.

The intraoral antimicrobial activity of four commercial oral products-conventional NaF dentifrice (Crest), baking soda/peroxide/NaF dentifrice (Mentadent), essential oil mouthrinse (Listerine) and SnF2 dentifrice (Crest Plus Gum Care)-have been compared in three test regimens. Formulations were compared for their ability to suppress the regrowth and apical extension of dental plaque following toothbrushing during thirty hours of non-brushing where products were used as oral rinses (30-hour plaque regrowth model). Formulations were also compared for their ability to suppress the colony-forming units (cfu) of facultative anaerobic bacteria sampled from buccal gingival surfaces following use (Gingival Surface Microbial Index-GSMI model). Lastly, formulations were compared for effects in suppressing the glycolytic metabolic activity and regrowth activity of in vivo-treated dental plaques sampled at various periods following topical use and incubated under controlled ex vivo conditions (Plaque Glycolysis and Regrowth-PGRM model). In thirty-hour plaque regrowth testing, the rank ordered antimicrobial efficacy of formulations followed SnF2 > essential oils > NaF = water = baking soda/peroxide. In GSMI testing, all formulations were shown to suppress the cfu of facultative anaerobic bacteria relative to baseline, although SnF2 treatment was observed to reduce bacterial levels to a significantly greater degree than NaF dentifrice or baking soda/peroxide dentifrice up to two hours following brushing. In PGRM testing, the SnF2 dentifrice provided significant inhibition of bacterial metabolism and regrowth following topical application when compared with the NaF dentifrice as control. The baking soda/peroxide dentifrice provided no reduction in either bacterial metabolism or regrowth in PGRM. Previous studies had demonstrated modest effects for essential oil rinse in reducing PGRM plaque regrowth, with no effects for this treatment on plaque metabolism. Overall, these results demonstrate that SnF2 dentifrice provides substantial intraoral antimicrobial effects. The essential oil mouthrinse also exhibits significant intraoral antimicrobial effects, albeit apparently less than SnF2 dentifrice. The baking soda/peroxide dentifrice did not produce any antimicrobial effects following in vivo use compared with conventional dentifrice. These results provide mechanistic rationale for the chemotherapeutic efficacy of SnF2 and essential oil formulations in reducing gingivitis, while providing no support for the expectation of clinical efficacy for formulations containing baking soda and peroxide.

Adult↗
PubMed1997

Innervation of extraocular pulley smooth muscle in monkeys and humans.

PURPOSE: Soft pulleys stabilize paths and determine pulling directions of the extraocular muscles (EOMs). This study was conducted to characterize innervation of smooth muscles (SMs) supporting these pulleys. METHODS: Cadaveric human and monkey orbits were step and serially sectioned for histochemical and immunohistochemical staining. Before perfusion, the superior cervical ganglia of one monkey had been injected with the anterograde tracer Phaseolus vulgaris leukoagglutinin (PHA-L). Immunoperoxidase staining to human SM alpha-actin confirmed pulley SM. Monoclonal and polyclonal antibodies were used to demonstrate PHA-L, tyrosine hydroxylase, dopamine beta-hydroxylase, phenylethanolamine-N-methyltransferase, neuronal nitric oxide synthase (NOS), and synaptophysin. The NADPH-diaphorase reaction was also used as a marker for NOS and the acetylcholinesterase (AChE) reaction for acetylcholine. RESULTS: Pulleys, consisting of collagen and elastin sleeves supported by connective tissue containing SM, were observed around rectus muscles of humans and monkeys. The human and monkey SM was richly innervated. Axons terminating in motor end plates within SM bundles were immunoreactive to PHA-L, tyrosine hydroxylase, and dopamine beta-hydroxylase, but not phenylethanolamine-N-methyltransferase, indicating innervation of pulley SM from the superior cervical ganglion by projections using norepinephrine. Smaller axons and motor end plates were also demonstrated in SM, using NADPH-diaphorase and NOS immunoreactivity, indicating nitroxidergic innervation, and using AchE, indicating cholinergic parasympathetic innervation. The pterygopalatine and, to a lesser extent, the ciliary ganglia, but not the Edinger-Westphal nucleus, contained cells immunoreactive to NOS, suggesting that nitroxidergic innervation to pulley SM is mainly from the pterygopalatine ganglion. CONCLUSIONS: The SM suspensions of human and monkey EOM pulleys are similar and receive rich innervation involving multiple neurotransmitters. These complex projections suggest excitatory and inhibitory control of EOM pulley SM, and support their dynamic role in ocular motility.

Acetylcholinesterase↗
PubMed1997

Amputation for infection or ischemia.

Successful limb salvage for infection or ischemia is dependent on the surgeon's ability to stabilize the acute process and select a level of amputation that will result in predictable healing potential and functional longevity. These patients often have multiple medical problems and significant social issues that must be considered in their overall care. This article presents current concepts in limb salvage surgery and reviews wound healing parameters to assist the surgeon in selecting the appropriate level of amputation for these patients.

Aftercare↗
PubMed1996

Electrically evoked cubic distortion product otoacoustic emissions from gerbil cochlea.

It has been demonstrated that electrical stimulation of the cochlear partition results in basilar membrane vibration and otoacoustic emissions. Electromotility of stimulated outer hair cells (OHCs) elicits the electrically evoked otoacoustic emissions (EEOAEs). Although electrically evoked upper and lower sideband distortion products (DPs) have been reported, electrically evoked cubic DP has not been investigated. Since the acoustically evoked cubic DP is the most commonly used otoacoustic measure of cochlear nonlinearity, this study tested whether electrical stimuli evoke a cubic DP otoacoustic emission. An electrical current containing the frequency component f1 and f2 (f1 < f2) was delivered to the round window niche of the gerbil, and electrically induced sound pressure change in the external ear canal was measured with a microphone. It was found that, in addition to f1 and f2 EEOAEs, cubic DP (2f1-f2) and other emissions at 3f1-2f2, 2f2-f1 and f2-f1 frequencies are electrically evoked. The electrically evoked cubic DP growth is similar to that of an acoustically evoked cubic DP. An electrical stimulus at f1 or f2 and an acoustic stimulus at f2 or f1 produce an identical cubic DP to that evoked by two electrical stimuli and/or two acoustic stimuli at f1 and f2 frequencies. An acoustic suppressor at a frequency near f2 can completely suppress an electrically evoked cubic DP emission. These data demonstrate that DPs can be provoked by a complex two frequency electrical current delivered to the round window niche. These stimuli elicit mechanical vibrations, from stimulated OHCs near the round window, which propagate apically toward their characteristic frequency places on the basilar membrane, and produce combination DPs. Electrically evoked cubic DPs appear to be produced by the same nonlinear mechanism that generates acoustically evoked DPs.

Acoustic Stimulation↗
PubMed1996

Eliminating bradyarrhythmias after orthotopic heart transplantation.

BACKGROUND: Bradycardia and sinus node dysfunction are common causes of early postoperative morbidity in orthotopic heart transplant recipients and frequently require the use of chronotropic drugs or permanent pacemakers. Several causes have been postulated, including surgical trauma to the sinus node and its blood supply. We sought to eliminate sinus node dysfunction and postoperative bradyarrhythmias by altering the orthotopic heart transplantation technique. METHODS AND RESULTS: Seventy orthotopic heart transplant recipients underwent electrophysiological testing of sinus node function a mean of 9 +/- 3 days after surgery. Standard (atrial anastomosis) orthotopic heart transplantation was performed in 33 patients; total (bicaval anastomosis) heart transplantation was performed in 37 patients. Abnormalities of sinus node function were present in 14 of 33 patients (42%) undergoing standard orthotopic heart transplantation compared with 2 of 37 patients arrhythmia (5%) in whom total heart transplantation was performed (P < .005). The resting sinus heart rate of patients with a normal sinus rhythm was also significantly higher in the total heart transplantation group (90 +/- 12 versus 83 +/- 14 bpm, P < .05). Coronary angiography was performed before discharge in 63 patients. Eleven were found to have an abnormal sinoatrial nodal artery, and 7 of these patients also had evidence of sinus node dysfunction (P < .005). CONCLUSIONS: Surgical trauma to the donor sinus node and/or its blood supply is a significant cause of sinus node dysfunction in the orthotopic heart transplant recipient. By use of a bicaval anastomotic technique, the incidence of and need for treatment of postoperative bradyarrhythmias can be significantly reduced.

Adult↗
PubMed1996

Replication and pathogenicity after intranasal and intracranial inoculation of swine with a recombinant pseudorabies virus containing a deletion at the UL/IR junction.

Pseudorabies virus (PRV) is a neurotropic herpesvirus of swine. Previously, we described construction of a recombinant strain of PRV (LLT beta delta 2) which contains a 3.0-kb deletion spanning the junction of the unique long and internal repeat sequences. Compared to the parental strain, Indiana-Funkhauser, and a virus rescued for the deleted sequences (LLT beta res), LLT beta delta 2 replicated efficiently at the site of inoculation, yet exhibited significantly reduced virulence when inoculated intranasally in pigs. In this report, we investigated the effect of the deletion on PRV replication and virulence after intracranial inoculation of swine, in comparison to replication and virulence after intranasal inoculation, in order to more precisely locate the defect in LLT beta delta 2. Four-day-old pigs were infected intranasally with LLT beta delta 2 or LLT beta res and necropsied at various times postinfection. Compared to LLT beta res-infected pigs, tissue distribution of virus, PRV antigen, and lesions of LLT beta delta 2-infected pigs were comparable in all peripheral tissues examined, including trigeminal ganglia, but were reduced in tissues from the central nervous system (CNS). LLT beta delta 2 was able to replicate in the CNS after intracranial inoculation into the cerebral cortex of 2-day-old piglets and to spread from CNS to peripheral tissues. Neurovirulence of LLT beta delta 2 was somewhat reduced, as demonstrated by delayed onset of neurological signs and death in intracranially inoculated pigs. These results indicate that decreased neurovirulence after intranasal inoculation is not due to inability of LLT beta delta 2 to replicate in CNS tissues. The difference in the amount of antigen detected in CNS tissues after intracranial inoculation compared to intranasal inoculation suggests that one defect in LLT beta delta 2 is reduced ability to spread from peripheral neurons to the CNS after intranasal inoculation.

Animals↗
PubMed1996

TCR-mediated adhesion of T cell hybridomas to planar bilayers containing purified MHC class II/peptide complexes and receptor shedding during detachment.

T cell recognition of foreign Ag/MHC class II complexes is sensitive down to approximately 100 complexes per cell or approximately 0.2 complexes/micron2. To better understand the physical basis of the recognition stage of Ag presentation, we examined adhesion of the lysozyme- specific T cell hybridoma, 3A9, to artificial bilayers containing covalent MHC class II/peptide complexes or adhesion molecules. Adhesion of 3A9 cells required a superphysiologic density of the MHC class II/peptide complex and was partly dependent on CD4; cells adhered but did not crawl. No adhesion was observed to bilayers containing MHC class II molecules without the lysozyme peptide. Activated 3A9 cells adhered and crawled on bilayers containing ICAM-1. The physical strength of contacts was tested with fluid shear. 3A9 cells adherent to bilayers containing MHC class II/peptide complexes shed their contact, which remained on the substrate and contained TCR. In contrast, 3A9 cells peeled from the ICAM-1 bilayer, and held firmly on LFA-1 bilayers; in a manner dependent on filamentous actin. When ICAM-1 and the MHC/peptide complexes were combined, the 3A9 cells adhered tightly and spread, but did not crawl, on the bilayers and TCR clustered at the center of the contact area. Physiologically, the TCR is unlikely to directly initiate adhesion. TCR clusters formed with the assistance of adhesion mechanisms may have to be shed to allow de-adhesion, and this may contribute to TCR down-regulation.

Animals↗
PubMed1996

Adhesion-activating phorbol ester increases the mobility of leukocyte integrin LFA-1 in cultured lymphocytes.

Lymphocytes activate adhesion to intracellular adhesion mlecule 1 (ICAM-1) via leukocyte function associated antigen 1 (LFA-1), their major beta 2 integrin, in response to PMA (phorbol 12-myristate 13-acetate) without an increase in the number of receptors expressed. The molecular details of the mechanism are unknown. To determine the effect of PMA activation on LFA-1 movement within the plasma membrane, we used the single particle tracking technique to measure the diffusion rate of LFA-1 molecules on EBV-transformed B cells before and after PMA activation. Diffusion of LFA-1 on unactivated cells was restricted compared to CR1 (CD35), another transmembrane protein of equivalent size. PMA caused a 10-fold increase in the diffusion rate of LFA-1 without any effect on CD35. The increased LFA-1 motion induced by PMA was random, not directed, indicating that it was due to a release of constraints rather than the application of forces. The diffusion rates of LFA-1 are consistent with cytoskeletal attachment before and free diffusion after PMA. Cytochalasin D led to an equivalent increase in mobility and, at low doses, stimulated adhesion, implying that the nonadhesive state of LFA-1 is actively maintained by the lymphocyte cytoskeleton.

Biological Transport↗
PubMed1996

Egocentric localization of a perisaccadic flash by manual pointing.

Reaching towards a visual object in the absence of visual referents relies on a chain of information, from the sensory signals encoding the object's image on the retina, to the motor signals driving the hand. One link in this chain is an extraretinal eye position signal (EEPS), which specifies the position of the eye in the head. EEPS must be updated in precise coordination with the eye's rapidly changing position, or perisaccadic visual targets will be mislocalized. There have been conflicting reports about the existence and nature of mislocalizations associated with saccades. We measured perisaccadic visual localization by presenting brief (250 microseconds), bright (6000 cd/m2), binocular, gaze-point (foveal) probe flashes in an otherwise dark field to normal human subjects instructed to point to them with an unseen hand. Saccade and fixation targets were auditory, making intravisual comparison impossible. Saccades, elicited randomly to left and right of straight ahead, had a mean magnitude of 8.9 deg. Control trials, employing only non-perisaccadic probes and providing feedback of pointing errors, were randomly interspersed, to monitor and control drift of hand-eye coordination. On average, localization began to shift for probes presented 2 msec after the eye began to move, reaching a stable post-saccadic value with time constant tau = 71 msec. A second experiment was similar, except that viewing was monocular, and probes were presented randomly, at gaze (on fovea), 6 deg left of gaze (right of fovea) and 6 deg right of gaze (left of fovea). The main analysis treated saccades larger than 8 deg: their mean magnitude was 12.9 deg. Flashes left of gaze were relocalized faster (tau = 65 msec) than flashes right of gaze (tau = 129 msec) around the time of leftward saccades. In contrast, flashes right of gaze were relocalized faster (tau = 62 msec) than flashes left of gaze (tau = 90 msec) around the time of rightward saccades. Time constant was independent of saccade size. Updating began for probes presented within 4 msec of the beginning of saccades, and was not a function of saccade or flash direction. Thus, there were no systematic mislocalizations of probes presented before eye movement, and large mislocalizations of probes presented during and after. Mislocalizations were, on average, always in the direction opposite the saccade, and were maximal (about half the magnitude of the completed saccade) near the end of the saccade. Stable post-saccadic localization was not achieved until about 100-300 msec after completion of a saccade; EEPS was updated slowly, compared to eye position itself. The visual field was not remapped uniformly: the side that would normally contain the target of a visually evoked saccade (and usually the target of a corrective saccade), was updated with a shorter time constant.

Humans↗
PubMed1996

Nitric oxide mediates capsaicin-induced increase in cochlear blood flow.

Capsaicin has been previously shown to increase cochlear blood flow (CBF) in a dose-dependent manner. The aim of this study was to define the role of nitric oxide (NO) in capsaicin-induced changes in CBF. This was investigated in the anesthetized guinea pig, utilizing laser Doppler flowmetry. Application of capsaicin (64.8 and 6.48 nmol in 2 microliters of saline) to the round window membrane (RWM) caused increases in CBF (34 +/- 2.8% of baseline (BL) and 28 +/- 2.3% BL, respectively (P < 0.001)). Application of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg intravenously or topically to the RWM) reduced blood flow in the cochlea, as previously reported. After pretreatment with i.v. L-NAME, the effect of capsaicin on CBF was significantly decreased. With the dose of capsaicin at 64.8 nmol, the increase in CBF fell from 34 +/- 2.8% BL to 6.9 +/- 1.5% BL (P < 0.001), and at 6.48 nmol it fell from 28 +/- 2.3% BL to 4.8 +/- 1.6% BL (P < 0.001). RWM L-NAME application also decreased the capsaicin vasodilatation effect. A capsaicin dose of 64.8 nmol resulted in only a 10 +/- 2.5% BL increase in CBF, and with 6.48 nmol capsaicin the increase was 7.8 +/- 2.2% of BL (P < 0.001). Capsaicin-sensitive sensory neurons in other systems are generally known to release substance P (SP), which in turn elicits release of endothelium derived relaxing factor (NO). The results of this study indicate that NO is a mediator of capsaicin-sensitive sensory neuronal function in CBF regulation.

Animals↗
PubMed1996

Optical modeling of radial keratotomy incision patterns.

PURPOSE: To determine the optical effects of higher-order corneal shape variations resulting from radial keratotomy. METHODS: Videokeratoscopic height data were obtained postoperatively from several patients who had undergone radial keratotomy. For each of clear central zone sizes 3.00 mm, 4.00 mm, and 4.75 mm, two patients were chosen randomly from the larger study group. Data obtained 2 weeks postoperatively from these six patients were decomposed into the Zernike polynomials, and the low-order expansion terms were removed to disclose corneal height variations (the radial keratotomy artifact). The artifact was applied to a schematic eye model, and exact ray-tracing was used to evaluate visual performance, which was defined as a function of pupil diameter, optical zone (central clear zone) size, and radial keratotomy artifact centration. RESULTS: The radial keratotomy artifact degrades visual performance at midspatial frequencies more than it does at high spatial frequencies. This effect is most pronounced for smaller optical zones and for a pupil diameter of 4 mm. Visual performance remains nearly constant for small decentration (0.5 mm or less) of the radial keratotomy optical zone from the corneal apex. CONCLUSIONS: Residual refractive error, corneal asphericity, and the radial keratotomy artifact all affect visual performance after radial keratotomy. Isolated effects of the radial keratotomy artifact degrade visual performance, with the level of degradation dependent on pupil size, optical zone size, and centration of the procedure. More research is necessary to combine the radial keratotomy artifact with changes in corneal asphericity and to further quantify the optical effects of radial keratotomy.

Contrast Sensitivity↗