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Biomedical subjects

J M Miller

Publications and source records attributed to J M Miller.

At least 163 records · Page 9Linked to original sources

Isolation of Enterobacter intermedium from the gallbladder of a patient with cholecystitis.

We describe the isolation and identification of Enterobacter intermedium from the gallbladder of a patient with cholecystitis. There have been only four documented isolations of this organism from humans; it normally occurs in surface water and unpolluted soils. The identification was initially made by a MicroScan Walk/Away system with a Neg Combo 18 conventional identification-susceptibility panel. The organism is susceptible to the aminoglycosides and imipenem but resistant to the cephalosporins and ciprofloxacin.

Anti-Bacterial Agents↗

Monoclonal antibody F89/160.1.5 defines a conserved epitope on the ruminant prion protein.

The transmissible spongiform encephalopathies are a heterogeneous group of fatal neurodegenerative disorders occurring in humans, mink, cats, and ruminant herbivores. The occurrence of novel transmissible spongiform encephalopathies in cattle in the United Kingdom and Europe and in mule deer and elk in parts of the United States has emphasized the need for reliable diagnostic tests with standardized reagents. Postmortem diagnosis is performed by histologic examination of brain sections from affected animals. The histopathological criteria for transmissible spongiform encephalopathies include gliosis, astrocytosis, neuronal degeneration, and spongiform change. These lesions vary in intensity and anatomic location depending on the host species and genetics, stage of disease, and infectious agent source. Diagnosis by histopathology alone may be ambiguous in hosts with early cases of disease and impossible if the tissue is autolyzed. Deposition of the prion protein (an abnormal isoform of a native cellular sialoglycoprotein) in the central nervous system is a reliable marker for infection, and immunohistochemical detection of this marker is a useful adjunct to histopathology. In the present paper we describe monoclonal antibody (MAb) F89/160.1.5, which reacts with prion protein in tissues from sheep, cattle, mule deer, and elk with naturally occurring transmissible spongiform encephalopathies. This MAb recognizes a conserved epitope on the prion protein in formalin-fixed, paraffin-embedded sections after hydrated autoclaving. MAb F89/160.1.5 will be useful in diagnostic and pathogenesis studies of the transmissible spongiform encephalopathies in these ruminant species.

Amino Acid Sequence↗

Age-related changes in cochlear blood flow response to occlusion of anterior inferior cerebellar artery in mice.

Previous studies suggest that autoregulation of cochlear blood flow (CBF) may be impaired by aging. In this study, we quantified the capacity of CBF autoregulation in young adult (6-month-old) and aged (21-month-old) CBA mice, to examine the effect of aging on CBF autoregulation. The technique of anterior inferior cerebellar artery (AICA) occlusion was employed to manipulate cochlear perfusion pressure. The CBF was measured by laser Doppler flowmetry during intermittent occlusion of the AICA with a microvascular clamp, which causes an initial decrease in CBF. The autoregulation of CBF was evaluated by quantifying the CBF increase (compensatory dilatory response in the cochlear vessels) during AICA occlusion. Our results demonstrated that autoregulation of CBF was significantly reduced and that collateral vascular function supplying CBF was significantly lower in the aged group. These findings suggest that the aged ear has less capacity to maintain stable blood flow and thus may be more vulnerable to stress factors that affect cochlear function.

Age Factors↗

Recognizing and managing Clostridium difficile-associated diarrhea.

Clostridium difficile-associated diarrhea poses a significant physical risk and cost to the recovery of hospitalized older adults. C. difficile is responsible for 75% or more of the diarrhea-associated enteric infections acquired during a hospital stay (Gerding, Johnson, Peterson, Mulligan, & Silva, 1995). C. difficile is easily spread by direct or indirect contact, therefore placing other patients at great risk for contamination by this organism. Nursing plays a significant role in early identification, management, and control of the spread of this potentially lethal infection.

Adult↗

The impact of specimen management in microbiology.

Because the way specimens are collected and handled may directly affect the outcome of microbiological analysis, appropriate specimen management is critical to ensuring laboratory effectiveness and an acceptable turnaround time. Specific guidelines on specimen collection are necessary for optimal use of microbiology services.

Blood Specimen Collection↗

Displacement of the medial rectus pulley in superior oblique palsy.

PURPOSE: The rectus extraocular muscles pass through fibromuscular connective tissue pulleys that stabilize muscle paths and control the direction of muscle pull. The authors investigated whether abnormal forces associated with superior oblique palsy can cause displacement of pulleys and muscle paths. METHODS: Coronal magnetic resonance imaging (MRI) showing significantly reduced superior oblique cross-sectional areas and lack of contractile changes with vertical gaze confirms that seven subjects had superior oblique palsies. Binocular misalignment was quantified using the Hess test. In those seven subjects with palsies and in 18 normal orbits, coronal MRI scans corrected to standardized head position were analyzed digitally to determine muscle paths in primary gaze. Horizontal and vertical coordinates of the pulleys, known histologically to lie just posterior to the equator in primary gaze, were inferred from these muscle paths. RESULTS: Normal pulley coordinates were highly uniform. Compared with both normal orbits and fellow orbits, orbits with superior oblique palsies showed a statistically significant 1.1 mm superior displacement of the medial rectus pulley. No other pulley was displaced significantly from normal. Computer simulation using a biomechanical model of ocular statics showed that, in each case, the pulley position shifts alone were insufficient to reproduce the clinical pattern of strabismus. CONCLUSIONS: The excyclotorsion of the globe that accompanies superior oblique palsy does not systematically displace the pulleys of all the rectus muscles. The only significant rectus muscle path change is for the medial rectus muscle, and it may arise as a mechanical consequence of the atrophy of the adjacent superior oblique muscle belly. Biomechanical modeling suggests that this displacement of the medial rectus pulley alone does not account for the pattern of strabismus observed in superior oblique palsy.

Adolescent↗

Interactive effects of aging with noise induced hearing loss.

Aging is associated with a down-regulation in metabolism, which may underlie an increased sensitivity to stress agents and a decreased repair of tissues following stress. In the auditory system this could lead to increased sensitivity to noise induced hearing loss (NIHL) with age. This study examines the effects of high intensity noise exposure (0.5-40 kHz noise at 108 dB SPL for 45 min) on young and old normal (CBA/Ca) mice and young premature presbycusis (C57BL/6) mice. Tone evoked auditory brainstem response (ABR) audiograms were obtained before and after the exposure. The animals were sacrificed and cytocochleograms were performed. The ABR threshold shifts and hair cell losses which followed noise exposure increased with increasing age in the normal (CBA/Ca) mice. Subjects which showed early presbycusis (C57BL/6) associated with vascular pathology, showed an increased sensitivity to noise induced hearing loss over normal subjects. Interestingly, in some cases the physiological loss in C57BL/6 mice was not associated with hair cell loss. These findings support the view that aging with or without hearing loss increased the sensitivity of the ear to NIHL. However, it seems that other factors may contribute to NIHL in the animals with premature presbycusis.

Aging↗

Evaluating physical and behavioral changes in older adults.

In older adults, subtle and sometime not so subtle physical or behavior changes can act as early warning signs of changing status. Nonspecific signs and symptoms occurring in older adults such as decline in previous functional capacity, urinary incontinence, anorexia, confusion, or unexplained falls may be signs of infection, medication interaction, dehydration, constipation, or sleep deprivation. Nurses, by critically assessing the situation early, may identify a developing problem. Prompt and early diagnosis of the underlying problem may save costly extended hospitalization or even prevent life-threatening complications.

Aged↗

Human autoantibodies and monoclonal antibody KHRI-3 bind to a phylogenetically conserved inner-ear-supporting cell antigen.

Autoimmunity is thought to be one cause of sensorineural hearing loss (SNHL). Sera from patients with rapidly progressive hearing loss have been shown to contain antibodies to a 68-kD protein in heterologous inner-ear tissue. Using guinea pig inner-ear tissue as the antigenic substrate and either Western blot or immunofluorescence (IF) or both, we tested sera from 74 patients suspected to have autoimmune hearing loss for inner-ear antibodies. Sera from 73 patients were tested by Western blot, and sera from 36 were tested by IF. Thirty-seven of 73 (51%) had antibody to a 68-70-kD protein by Western blot. Sera positive by IF stained supporting cells with a staining pattern like that previously observed with the KHRI-3 monoclonal antibody. There was concordance between Western blot and IF assays. Of 36 patients tested by both assays, 29/31 (94%) that were positive in Western blot were also positive by IF, three were negative by both tests, and two each were positive by one assay but negative by the other. Absorption of patient sera with human inner-ear tissue removed antibody reactivity to the guinea pig supporting cells, indicating that the antigen detected by the autoantibody is also present in the human inner ear. Absorption with an equal volume of white or red blood cells from the tissue donor did not remove the antibody reactivity to inner ear, showing that the absorption by inner-ear tissue is specific. Sera from three patients positive in both assays also stained a 68-70-kD inner-ear protein immunoprecipitated by the KHRI-3 monoclonal antibody, indicating that the monoclonal and human antibodies recognize the same antigen. The results support the hypothesis that patients with autoimmune sensorineural hearing loss produce autoantibodies to an inner-ear supporting cell antigen that is phylogenetically conserved and defined by the murine monoclonal antibody KHRI-3. Since KHRI-3 can induce hearing loss after infusion into the inner ear, it is likely that autoantibodies with the same antigenic target are also pathogenic in humans.

Animals↗

Low affinity interaction of human or rat T cell adhesion molecule CD2 with its ligand aligns adhering membranes to achieve high physiological affinity.

The mechanism by which low affinity adhesion molecules function to produce stable cell-cell adhesion is unknown. In solution, the interaction of human CD2 with its ligand CD58 is of low affinity (500 mM-1) and the interaction of rat CD2 with its ligand CD48 is of still lower affinity (40 mM-1). At the molecular level, however, the two systems are likely to be topologically identical. Fluorescently labeled glycosylphosphatidylinositol-anchored CD48 and CD58 were prepared and incorporated into supported phospholipid bilayers, in which the ligands were capable of free lateral diffusion. Quantitative fluorescence imaging was used to study the binding of cell surface human and rat CD2 molecules to the fluorescent ligands in contact areas between Jurkat cells and the bilayers. These studies provide two major conclusions. First, CD2/ligand interactions cooperate to align membranes with nanometer precision leading to a physiologically effective two-dimensional affinity. This process does not require the intact cytoplasmic tail of CD2. Second, the degree of membrane alignment that can be achieved by topologically similar receptors deteriorates with decreasing affinity. This suggests an affinity limit for the ability of this mode of cooperativity to achieve stable cell-cell adhesion at approximately 10 mM-1.

Animals↗

Radiofrequency catheter ablation of postinfarction ventricular tachycardia: long-term success and the significance of inducible nonclinical arrhythmias.

BACKGROUND: Radiofrequency (RF) catheter ablation is effective therapy for monomorphic ventricular tachycardia (VT) in patients without structural heart disease. In patients with postinfarction VT; however, this procedure has been used predominantly as adjunctive therapy, targeting only the patient's clinically documented arrhythmia. By targeting all inducible, sustained VT morphologies, we sought to determine the utility of RF catheter ablation as a primary cure in patients who present with hemodynamically tolerated VT. METHODS AND RESULTS: RF ablation was attempted in 35 patients with a previous myocardial infarction and recurrent, hemodynamically tolerated VT. A mean of 3.9+/-2.7 VTs were induced per patient (range, 1 to 10). The clinically documented arrhythmia was successfully ablated in 30 of 35 patients (86%), and on follow-up electrophysiological testing, 11 patients had no inducible VT and were discharged without other therapy. Nineteen patients had inducible "nonclinical" arrhythmias on follow-up testing, and the majority underwent cardiac defibrillator implantation. Freedom from recurrent arrhythmias, including sudden death, was 91% in patients without inducible VT and 53% in patients with persistently inducible "nonclinical" arrhythmias (P<.05; mean follow-up, 17+/-12 and 12+/-11 months, respectively). CONCLUSIONS: In patients with well-tolerated VT, RF catheter ablation may be useful as a primary cure if no other ventricular arrhythmias are inducible on follow-up testing. Ablation of all hemodynamically tolerated arrhythmias should be attempted in patients with multiple inducible VT morphologies because of the high rate of recurrence of unablated VTs in these patients.

Aged↗

Growth stage dependent effects of electromagnetic fields on DNA synthesis of Jurkat cells.

A 1.8 mT, bone healing, electromagnetic field (EMF) and power frequency EMFs of 0.1 and 0.4 mT significantly inhibit DNA synthesis in otherwise unstimulated Jurkat (E 6.1) cells. Inhibition is generally most prominent in cells from mid log phase growth. In complete medium the bone healing EMF inhibits [3H] thymidine uptake of the latter cells by almost 50% vs. 20-25% inhibition by 60 Hz fields. Cells in conditioned medium are even more sensitive to EMFs with inhibition up to ca. 60%. The effects of the 0.1 and 0.4 mT power frequency EMFs were very similar suggesting saturation at 0.1 mT or lower.

Cell Division↗

Low affinity of cell surface lymphocyte function-associated antigen-1 (LFA-1) generates selectivity for cell-cell interactions.

We examined binding of soluble intercellular adhesion molecule-1 (ICAM-1) dimers and a range of ICAM-1-coated particles to activated T cells. Lymphocyte function-associated antigen-1 (LFA-1) on the surface of activated T cells did not bind soluble ICAM-1 dimers with high affinity. In contrast, activated T cells adhered avidly to ICAM-1-coated planar surfaces. Between these two extremes, a range of ICAM-1-bearing particles was tested for binding. Activated T cells bound particles of 1-microm diameter or larger, but did not bind particles of 0.5-microm diameter or smaller. This threshold was eliminated, and all forms of ICAM-1 bound to LFA-1 when LFA-1 was converted to a high affinity form with an activating antibody. We show that high affinity LFA-1 is generated only as a consequence of an initial low affinity interaction of LFA-1 with ICAM-1 under physiological conditions. Therefore, the selectivity of cell surface LFA-1 for cell-sized particles bearing ICAM-1 appears to be due to the maintenance of low affinity LFA-1 on the surface of activated T cells. These findings alter the definition of inside-out signaling for LFA-1.

Cell Adhesion↗

Developmental analysis and subcellular localization of the murine homologue of ELL.

The ELL gene was first identified by its involvement with MLL in the translocation (11;19)(q23;p13.1) in acute myeloid leukemia. To date, nine other MLL partner genes have been cloned, but their precise functions have yet to be determined. To characterize the functions of ELL further, we have cloned the murine homologue of ELL and have found that the gene is highly conserved at the nucleotide and amino acid level. The open reading frame of the murine homologue contains 602 aa, slightly smaller than the 621 aa in the human gene. With Northern blot analysis, a 3.4-kb transcript is detected in all tissues examined with greatest levels of expression in the liver. Unlike human ELL, only a single transcript can be detected with either murine coding sequence or 3' untranslated region probes. To examine the spatial and temporal pattern of expression in murine development, in situ hybridization studies were performed with sense and antisense riboprobes from the 3' untranslated region of murine Ell. Ell is expressed diffusely by embryonic day 7.5 (E7.5). In addition, high levels of expression can be detected in maternally derived decidual tissue. At E14.5, Ell is expressed diffusely throughout the embryo. However by E16.5, specific expression in the liver and gastrointestinal tract becomes prominent and remains so in both neonates and adults. To determine the subcellular localization of ELL, we developed a polyclonal antiserum to ELL that was used for immunofluorescence studies in COS-7, HeLa, NIH 3T3, and A7r5 cells. The ELL protein was localized to the nucleus but excluded from nucleoli in all cell lines examined. Recently, the gene product of ELL was found to function as an RNA polymerase II elongation factor, an activity that is consistent with our immunofluorescence data. Thus, these studies extend our understanding of the normal functions of ELL and provide additional insight into its aberrant function when fused to MLL in acute myeloid leukemia.

Acute Disease↗

The source of coagulase-negative staphylococci in the Endophthalmitis Vitrectomy Study. A comparison of eyelid and intraocular isolates using pulsed-field gel electrophoresis.

OBJECTIVE: To determine the species distribution of coagulase-negative staphylococci (CoNS) in patients with endophthalmitis and to ascertain whether the patient's own flora was a major source of postoperative endophthalmitis following cataract extraction. METHODS: In a 4-year multicenter prospective study, 524 bacterial isolates were submitted from 225 Endophthalmitis Vitrectomy Study patients. From the 524 isolates, 250 represented CoNS cultured from the anterior chamber, the vitreous, or both of the 225 patients. Where possible, paired isolates from an individual patient's eyelid and intraocular compartment(s) were studied by pulsed-field gel electrophoresis, an established molecular strain-typing technique. RESULTS: From all sites the most frequently isolated CoNS were Staphylococcus epidermidis (81.9%) and Staphylococcus lugdunensis (5.9%). Where analysis was possible, eyelid isolates were indistinguishable from intraocular isolates in 71 (67.7%) of 105 comparisons. Non-S epidermidis CoNS caused postoperative endophthalmitis in 5 patients. Four of the 5 had postoperative endophthalmitis caused by S lugdunensis and 1 by Staphylococcus haemolyticus. CONCLUSIONS: Coagulase-negative staphylococci from the patient's periocular skin flora play a significant role in causing intraocular infections, and non-S epidermidis CoNS play a small but significant role. These results reinforce the necessity to follow stringent surgical site preparation prior to eye surgery.

Anterior Chamber↗

Langerhans cell histiocytosis with orbital involvement.

PURPOSE: To review three cases of Langerhans cell histiocytosis with orbital involvement that represent a significantly excessive incidence of this rare disease in one community. Current diagnostic criteria and therapeutic modalities related to Langerhans cell histiocytosis are reviewed. METHODS: Case reports. We present clinical, radiologic, histopathologic, and epidemiologic information on three patients with Langerhans cell histiocytosis. RESULTS: All three children, born within 18 months of one another, manifested rapidly progressive unilateral proptosis at age 2 years. By computed tomography, all had moderately enhancing lesions with involvement of the sphenoid bone and lateral orbit as well as the temporal lobe of the brain. All patients were treated with a combination of vincristine and prednisone, with variable resolution of their lesions. The occurrence of three cases in children born in Nogales, Arizona/ Mexico, suggests an incidence rate of 40 per million, which is approximately 26 times the expected rate (P = .0001). CONCLUSIONS: The extraordinarily high incidence and the concentration of cases in both time and space of this cluster implies that Langerhans cell histiocytosis may be a sentinel disease for unusual environmental exposures.

Antineoplastic Combined Chemotherapy Protocols↗

A low profile human tendon force transducer: the influence of tendon thickness on calibration.

An in vitro calibration method for human tendon force transducers using tendon thickness to predict the calibration factor has been previously proposed (An et al., 1990, J. Biomechanics 23, 1269-1271). However, changes in the calibration factor due to changing tendon geometry during repeated tendon loading are unknown. A new, low-profile transducer design that measures tendon thickness in the transducer, in situ, is developed. An empirical model estimating the transducer's calibration factor is developed using data from in vitro tension testing of 12 fresh frozen human finger flexor tendons. Each tendon is preseated with ten loading cycles before data collection. Using tendon thickness, the model predicts the measured calibration factor to within 0-15% (average 6%). During repeated loading of an in vitro tendon, the calibration factor changes 15% over the first ten cycles (0-50 N) due to the observed changing tendon thickness. After the first ten loading cycles the variability of the calibration factor is reduced to less than 1% for the next three loading cycles. Hence this new, modified in vitro calibration procedure with tendon preseating reduces the cycle-to-cycle variability caused by the associated change in the tendon thickness.

Calibration↗