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M L Miller

Publications and source records attributed to M L Miller.

At least 19 recordsLinked to original sources
PubMed1996

Epidermal cytokinetics, DNA adducts, and dermal inflammation in the mouse skin in response to repeated benzo[a]pyrene exposures.

Few studies have investigated the chronic cytokinetic effects of carcinogen exposure in the mouse skin. We report two experiments involving the repeated application of benzo[a]pyrene (BaP) to the dorsal skin of female Ha/ICR mice. In the first experiment, the cytokinetic, inflammatory, and DNA adduct responses were studied daily over a 9-day period encompassing the fourth and fifth weekly applications of BaP at doses of 16, 32, and 64 micrograms. The second experiment involved the same cytokinetic measurements at 1, 3, 5, and 8 months, and the weekly BaP doses were 4, 8, and 16 micrograms. The first study showed that after each application of 32 or 64 micrograms BaP, there was a wave of slow DNA synthesis in the epidermis which peaked at 24 hr, in coincidence with a wave of BaP-DNA adducts, followed by the appearance of dead and damaged keratinocytes. For the first few days after BaP application there was a depression in the mitotic rate which recovered several days before the next BaP application. There was a predominantly monocytic dermal inflammation throughout the observation period. In the second experiment, at the lower BaP doses, there was proliferative depression at 1 month, without dermal inflammation. With continued exposure, the proliferative depression changed to a dose-dependent increase in the rate of proliferation and dermal inflammation. The level of BaP-DNA adducts was followed in the 4 micrograms/week dose group, which showed a threefold increase after 4 months with the appearance of inflammation and heightened cell proliferation. These results suggest that the delayed inflammatory reaction, possibly based on a cell-mediated immune reaction to BaP, might have been responsible for the late cytokinetic responses and the associated increase in the level of BaP-DNA adducts.

Animals↗
PubMed1996

Differential effects of nonhydroxylated flavonoids as inducers of cytochrome P450 1A and 2B isozymes in rat liver.

Flavanone, flavone, and tangeretin differentially affected the activities of cytochrome P540 1A and 2B isozymes in rat liver. Flavone and, to a lesser extent, tangeretin, increased activities of ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, and pentoxyresorufin O-dealkylase (PROD), whereas flavanone mainly enhanced PROD activity. Immunoblot analysis indicated that flavone and tangeretin increased cytochrome P450 1A1, 1A2, and 2B1,2 forms, whereas flavanone only enhanced the cytochrome P450 2B isozymes. Northern blot study showed that flavone and tangeretin increased the level of the cytochrome P450 1A2 mRNAs. The concentration of the other mRNAs were slightly or not affected by flavonoids. These results suggest that the induction of P450 1A2 by flavone and tangeretin might involve a transcriptional and/or post-transcriptional mechanism.

Animals↗
PubMed1996

The clinical usefulness of the preoperative bleeding time.

OBJECTIVES: To determine the clinical utilization of the Simplate bleeding time test as a preoperative screen, to examine the clinical utilization of the bleeding time test by multiple surgical services, and to correlate the indicators of bleeding risk (bleeding history, thrombocytopenia, prolonged prothrombin time/activated partial thromboplastin time, increased creatinine, and medications known to interfere with platelet function) with the bleeding time and the occurrence of clinically significant perioperative bleeding. DESIGN: Retrospective data analysis. SETTING: A large tertiary-care hospital. PATIENTS: One hundred sixty-seven consecutive surgical patients tested for preoperative bleeding time. MAIN OUTCOME MEASURES: The occurrence of clinically significant perioperative bleeding and the positive and negative predictive value of the preoperative screening bleeding time test. RESULTS: Patients with a positive bleeding history were more likely to have an abnormal bleeding time (P = .04), but there was no statistically significant association between patients with an abnormal bleeding time and the other indicators of bleeding risk examined or the occurrence of clinically significant perioperative bleeding. The positive predictive value of the preoperative bleeding time was 5%, and the negative predictive value was 95%. CONCLUSIONS: Screening for preoperative bleeding time is not a reliable test for assessing the risk of clinically significant perioperative bleeding and should not be used for this purpose.

Bleeding Time↗
PubMed1995

Microvillar cells of the olfactory epithelium: morphology and regeneration following exposure to toxic compounds.

In recent years microvillar cells (MVC) have been identified in the olfactory epithelium of numerous species, including rodents, canines, and primates. However, there is no consensus on the morphologic or histochemical features of this cell, nor is the function of these cells currently known. Previous studies have examined MVC during development and in the mature olfactory epithelium, but not after toxic insult. A microvillar cell, defined by specific morphologic criteria, was studied in adult male Long-Evans rats exposed via inhalation to either 200 ppm methyl bromide for 4 h/day, 4 days/week for 2 weeks, or to 635 micrograms/m3 nickel for 6 h/day for 16 consecutive days, and sacrificed serially over several months. The pattern of recovery for MVC differed according to the severity and specificity of the insult to the olfactory epithelium. With methyl bromide, all cell types were completely depleted from olfactory epithelium immediately after injury, including MVC. MVC were slow to repopulate the epithelium, and appeared only when olfactory epithelium was complete in other respects. With nickel exposure, where the major effect was a gradual decrease in sustentacular cells with a thinning of the apical cytoplasm thickness, MVC showed a decline during exposure, but reappeared during recovery. In both cases, there was no difference in olfactory function, even when MVC were absent from the olfactory epithelium. A mature olfactory epithelium appears to be necessary to support the presence of this MVC, suggesting that it is not crucial to the regeneration processes or recovery of olfactory function, but perhaps plays some role, as yet undefined, in the unperturbed olfactory epithelium.

Animals↗
PubMed1995

Hairy elbows.

Explore the source record for details and available documents.

Child↗
PubMed1995

Behavioral, histological, and neurochemical effects of nickel (II) on the rat olfactory system.

Experimentally, inorganic, sulfated nickel compounds (Ni2+) have been shown to produce histological lesions in the nasal mucosa of rats, more specifically, atrophy of the olfactory epithelium. The present project was designed to assess the effects of inhalation of nickel sulfate hexahydrate on behavioral, histological, and neurochemical aspects of the olfactory system. Male Long-Evans rats were exposed to either background air (control) or 635 micrograms Ni/m3 for 16 consecutive days, 6 hr/day. Exposure resulted in selective lesions to the olfactory epithelium. The number of bipolar sensory receptor cells was slightly reduced and there was a significant decrease in the thickness of the olfactory epithelium. This was due primarily to a significant loss of the sustentacular cell population, with a thinning of the apical cytoplasm, concomitant with a reduction in the number of microvilli at the surface of these cells. Significant decreases in carnosine level, consistent with the nickel sulfate exposure, were observed. However, there were no changes in olfactory function as measured by either absolute threshold or two-oder discrimination tasks.

Administration, Inhalation↗
PubMed1995

Fever of unknown origin.

The causes of fever in a child can vary from minor brief illnesses to life-threatening infectious, malignant, or autoimmune diseases. The physician often has to evaluate children with fevers of as yet undiagnosed cause lasting fewer than 2 weeks, in whom it is important to determine whether localizing findings are present. Fever without localizing signs and fevers complicating chronic disease and resulting from specific localized infection are considered in the sections concerning infectious causes, immunodeficiency diseases, and rheumatic diseases. The diagnostic and therapeutic approaches to the child with both prolonged fever and fever of unknown origin are then discussed, with emphasis on rheumatic diseases.

Child↗
PubMed1995

Scleroderma in children.

Childhood scleroderma may present in a variety of clinical forms that differ in clinical presentation, extracutaneous features, clinical course, and outcome. All include hardening of the skin as a major feature. This article reviews these various entities, focusing on primarily the clinical features. In addition, current concepts regarding pathogenesis and treatment are discussed.

Adolescent↗
PubMed1995

Relationships between the nuclear membrane, nuclear pore complexes, and organelles in the type II pneumocyte.

Functional relationships among organelles of the type II cell are suggested based upon the proximity of organelles to specialized areas of the plasma- and nuclear membranes. In a two-dimensional morphometric analysis of the profiles of organelles in type II cells of the ferret and rat (and beagle dog), lamellar bodies were more likely to be located near the nuclear membrane than at the alveolar space (where exocytosis occurs). The size of lamellar body profiles was not correlated with distance from the nuclear membrane; however, large profiles were nearer the apical membrane, and smaller ones nearer the basement membrane. Profiles of highly branched mitochondria were 10 times more frequently associated with nuclear pore complexes than with the inter-pore nuclear membrane. Forty percent of all mitochondrial profiles were within 0.25 microns of the nucleus, 5% were within 0.02 microns and half of these appeared to touch the filaments of the nuclear pore complexes. The size of mitochondrial profiles was not correlated with distribution. In the ferret and rat, 8.6% and 2.5% respectively, of the nuclear pore complexes were associated with mitochondria. Sebaceous cells, from control mice, demonstrated a spatial distribution of granules which was size dependent but unrelated to the nuclear membrane.

Animals↗
PubMed1995

Transglutaminase cross-linking of the tau protein.

Tissue transglutaminase (EC 2.3.2.13) is a calcium-activated enzyme that cross-links specific substrate proteins into insoluble, protease-resistant, high molecular weight complexes. Because the neurofibrillary tangles in Alzheimer disease have similar biochemical characteristics, and because the microtubule-associated protein tau is the predominant component of these structures, the substrate properties of tau with respect to transglutaminase were investigated. Bovine tau and recombinant human tau isoforms rapidly form high molecular weight, cross-linked polymers on incubation with transglutaminase. Polyamine incorporation assays indicate that bovine tau is an excellent substrate of transglutaminase, with a Km of 10.4 +/- 2.2 microM and a Vmax of 40.9 +/- 4.5 nmol/mg of enzyme/min. Individual recombinant human tau isoforms are not equivalent with respect to transglutaminase, as the smallest isoform T3 (352 amino acids) is not as good a substrate as the larger isoforms T4 (383 amino acids) and T4L (441 amino acids). To determine which segments of the tau protein are susceptible to modification by transglutaminase, tau was labeled with [3H]putrescine by transglutaminase and proteolyzed with alpha-chymotrypsin, and the breakdown products were analyzed. These experiments demonstrate that the enzyme modifies tau at only one or a few discrete sites, primarily in the carboxyl half of the molecule. Thus, the reaction is specific for only a small number of the many glutamine residues in tau. Furthermore, a tau deletion construct (T264) containing a portion of the microtubule-binding domains, which is a substrate of transglutaminase, cannot be cross-linked by the enzyme. This provides evidence that the cross-linking reaction is specific, and requires that the substrates be appropriately associated for cross-linking to occur.

Alzheimer Disease↗
PubMed1995

The effect of a heparin removal filter on platelet aggregation studies in heparin-induced thrombocytopenia.

Patients having a heparin-associated platelet antibody who are receiving heparin at the time of testing for heparin-induced thrombocytopenia (HIT) by platelet aggregometry may exhibit aggregation in the negative control channel. Filtering plasma to remove the heparin in may produce a nonaggregating negative control channel. The effect of the Pall Hepchek (Pall Biomedical, East Hills, NY) heparin removal filter on platelet aggregation studies was evaluated. Samples were studied from 10 patients with clinically established HIT. The pre-filtration platelet aggregation studies were unequivocally positive for heparin antibody. The remainder of each sample was filtered and the aggregation studies were repeated. Of the four patients on IV heparin, only one remained positive post-filtration. Of the six patients receiving subcutaneous heparin or flushes, one remained strongly positive, one was borderline, and four became negative. Pall Hepchek heparin filtration unpredictably alters the results of platelet aggregation studies, and should not be used routinely to remove heparin in the presence of aggregation in the negative control.

Filtration↗
PubMed1995

Time course of airway hyperresponsiveness and remodeling induced by hyperoxia in rats.

The purpose of this study was to answer two questions concerning hyperoxia-induced airway hyperresponsiveness: 1) What is the time course of the development of airway hyperresponsiveness? 2) What is the relationship between the increase in responsiveness and smooth muscle area? Segments of intrapulmonary bronchi were isolated from male Sprague-Dawley rats that had been exposed to 80-85% O2 for a period of 1, 3, 5, or 7 days and from aged-matched control animals that breathed room air. Hyperoxia increased the sensitivity (log concentration or frequency that elicited a half-maximal response) and reactivity (maximum tension developed) of the airways to electrical field stimulation (EFS) after 3, 5, and 7 days; sensitivity to acetylcholine was not affected, but reactivity was increased after 7 days. Hyperoxia increased smooth muscle area beginning 5 days after commencing the exposure. After normalizing tension responses to smooth muscle area, reactivity of the airways to the stimuli was not different between the two groups, but sensitivity to EFS was still increased. The increase in reactivity observed after 5 and 7 days of exposure can be explained by an increase in smooth muscle area that occurred at these time points. The fact that the sensitivity of the airways to EFS remained increased after normalization, together with the fact that the increase in airway responsiveness after 3 days of exposure occurred at a time when smooth muscle area was not different from control, suggests that mechanisms other than increased smooth muscle area contribute to the development of hyperoxia-induced airway hyperresponsiveness.

Acetylcholine↗
PubMed1995

Refractory ceramic fibers activate alveolar macrophage eicosanoid and cytokine release.

Refractory ceramic fiber has been developed for industrial processes requiring materials with high thermal and mechanical stability. To evaluate the biological activity of this fiber, rat alveolar macrophages were exposed for < or = 24 h to 0-1,000 micrograms/ml of refractory ceramic fiber, crocidolite asbestos, silica (fibrogenic particles), or titanium dioxide (a nonfibrogenic particle), and eicosanoid, tumor necrosis factor-alpha (TNF), and lactate dehydrogenase release were measured. Particle dimensions were determined by electron microscopy. Radioactivity coeluting with leukotriene B4 (LTB4) and immunoreactive LTB4 and TNF release increased after refractory ceramic fiber and were similar in magnitude after asbestos but less than after silica. For example, the total [3H]eicosanoid release increased 3.9-fold after refractory ceramic fiber, 4.6-fold after asbestos, and 8.7-fold after silica. Refractory ceramic fiber and asbestos also have similar particle dimensions (diameter, length, and surface area). Inasmuch as macrophage-derived LTB4 and TNF are potent mediators in inflammatory events, including migration and activation of neutrophils, these findings suggest that refractory ceramic fiber can activate macrophages in vitro to release mediators relevant to in vivo findings of inflammation and fibrotic lung disease in laboratory animals.

Animals↗
PubMed1995

Presence of multiple anti-phospholipid antibody specificities in a pediatric population.

Thrombotic related events are thought to be associated with the presence of anti-phospholipid antibodies (APA). However, the association of anti-cardiolipin antibody is much weaker than the association with antibodies to other phospholipids. Much of the literature equates antiphospholipid antibodies and anticardiolipin antibodies because of the relationship of APA and false positive tests for syphilis. However, recently the presence of antibodies to naturally occurring phospholipids other than cardiolipin have been reported. In fact, some investigators report that antibodies to phosphatidylserine appear to correlate more closely to disease processes than anti-cardiolipin antibodies. We describe here the presence of non-anti-cardiolipin antiphospholipid antibodies in a pediatric population that lack anti-cardiolipin antibodies and demonstrate the association of these antibodies with thrombotic disease. Antibodies to phosphatidic acid were the most prevalent and correlated (p < .001) with thrombotic disease and idiopathic thrombocytopenia purpura. The rank order of prevalence of antibodies to phospholipids was phosphatidic acid, phosphatidylglycerol, phosphatidylinosital, phosphatidylserine, cardiolipin and phosphatidylethanolamine. Antiphospholipid antibodies of the three major sera isotypes were present in the positive sera examined. These descriptive findings suggest that the significance of APA other than anti-cardiolipin antibodies in pediatric patients should be further investigated.

Antibodies, Anticardiolipin↗