PubMed Health⌕ Search

Biomedical subjects

M L Miller

Publications and source records attributed to M L Miller.

At least 19 recordsLinked to original sources
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

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

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

Elements in the 5' flanking sequences of the mouse low-affinity NGF receptor gene direct appropriate CNS, but not PNS, expression in transgenic mice.

We have initiated a characterization of the cis-acting regulatory elements of the murine low-affinity NGF receptor (p75NGFR) gene. Despite studies in cultured cells that suggest the p75NGFR promoter is constitutive, a detailed analysis of this promoter in five lines of transgenic mice demonstrated a high degree of cell-type specificity: 8.4 kb of 5' flanking sequence directs expression of a lacZ reporter to retinal and CNS neurons normally expressing p75NGFR. A transgene with 470 bp of 5' flanking sequence is also expressed in the CNS, but its regulation is aberrant, with a loss of basal forebrain expression. In non-neural tissues, both transgenes were expressed only in the testis, kidney, anterior pituitary, and pancreatic islets; with the exception of the renal pattern of expression, transgene activity was confined to appropriate cells within these tissues. In contrast, although expression of both transgenes was prominent in adrenal medulla and gastrointestinal myenteric neurons, neither construct was active in several sensory or sympathetic ganglia that strongly express the endogenous p75NGFR gene, indicating that genetic elements necessary for expression in these neurons are not present in these promoter sequences. In addition, neither transgene was activated in Schwann cells during Wallerian degeneration of sciatic nerve. We conclude that regulation of the p75NGFR gene is complex, with the first 470 bp of 5' flanking sequence sufficient for expression in enteric and CNS neurons and additional elements within the first 8.4 kb of 5' flanking sequence required for restriction to appropriate CNS neurons. Further regulatory elements are possibly required for expression in at least some sensory and sympathetic neurons in the PNS and in Schwann cells. To identify potential regulatory elements in the 470 bp of 5' flanking sequence from the smaller transgene, we compared the sequences of equivalent regions from the mouse, rat, and human p75NGFR genes. This "phylogenetic footprint" identified conserved motifs potentially important for the regulation of this gene in the CNS.

Animals↗
PubMed1992

Comparative tumor-initiating ability of 7H-dibenzo(c,g)carbazole and dibenz(a,j)acridine in mouse skin.

N-heterocyclic aromatics are environmentally important carcinogenic pollutants produced by incomplete combustion of organic material. 7H-Dibenzo-(c,g)carbazole (DBC), is a potent skin and systemic carcinogen, whereas dibenz(a,j)acridine (DBA), is a carcinogen with local effects. Therefore, the overall objective of these studies was to determine the initiating ability of DBC and DBA in mouse skin using an initiation-promotion protocol. Acetone-, TPA- or BaP-treated animals were used as negative and positive controls, respectively. DBC, DBA or BaP (200 nmol) dissolved in acetone was applied once to the backs of thirty shaved Hsd:(ICR)Br female mice, followed 2 weeks later with 2 micrograms of TPA in 50 microliters of acetone applied twice a week for up to 24 weeks. Skin tumors developed in 26, 17 and 27 animals, respectively. DBC plus TPA produced a significant influx of dermal macrophages similar to that seen for BaP. Initiation with BaP, DBC or DBA moderated the effect of TPA on most other dermal parameters, particularly neutrophils. These data indicate that, DBC, with apparently different activation pathways than BaP shows similar tumor initiating ability and morphological changes as BaP.

Acetone↗
PubMed1992

Morphogenesis of Sindbis virus in three subclones of Aedes albopictus (mosquito) cells.

The morphogenesis of Sindbis virus in three Aedes albopictus subcloned cell lines was examined. Each line was distinguishable with respect to morphology, cytopathic response to infection, and progeny yield. C7-10 cells, which produced the highest titers of virus and exhibited the most severe cytopathic response, were characterized ultrastructurally by the presence of budding particles at the cell surface and at the membranes of internal vesicles. C6/36 cells, which displayed a moderate cytotoxic response, manifested similar features in response to Sindbis virus infection. Both cell types also produced a structure composed of an electron-dense matrix in which nucleocapsids were embedded. Internally matured virions were released by exocytosis from these cells. In addition to a lack of cytopathic effect, u4.4 cells also failed to exhibit obvious morphogenetic changes upon infection. Virus particles were occasionally seen within vesicles, but budding at the cell surface was not detected. The mechanism of release of internally matured virions was not apparent. These studies provide further evidence that these three subcloned mosquito cell lines represent different tissues in the larval or adult insect.

Aedes↗
PubMed1992

Immunocytometry and gene rearrangement analysis in the diagnosis of lymphoma in an idiopathic pleural effusion.

We report a patient with an idiopathic pleural effusion in whom the diagnosis of non-Hodgkin's lymphoma was established by immunocytometry of pleural fluid and confirmed by the detection of B-cell immunoglobulin gene rearrangement. Immunocytometry is a rapid, semi-automated laboratory method for phenotyping lymphoid cells by determining immunoglobulin and other cell surface antigen expression. This method defines the cell lineage (T or B cells) and the clonality (monoclonal or polyclonal) of a population of lymphocytes. The presence of a monoclonal population of lymphocytes can also be confirmed by recently developed molecular biologic techniques (e.g., Southern blotting) that provide the ability to detect rearrangements of the genes that encode either B-cell immunoglobulin proteins or T-cell antigen receptor proteins. To our knowledge, this case represents the first reported application of immunophenotypic and gene rearrangement analysis in a previously undiagnosed pleural effusion to establish the diagnosis of lymphoma. These relatively new laboratory methods may have a role in the evaluation of idiopathic lymphocytic pleural effusions.

Aged↗
PubMed1992

Treatment of systemic lupus erythematosus.

The past year continued to see both major studies and interesting case reports slowly add suggestions, if not absolute knowledge, concerning the treatment of systemic lupus erythematosus. The Lupus Nephritis Collaborative Study Group published two papers, one of which concerned the lack of efficacy of plasmapheresis in treating severe lupus nephritis. A related paper documented the utility of initial serum creatinine in predicting renal failure in patients enrolled in both arms of the plasmapheresis study. Patients in the study received high-dose oral prednisone and low-dose oral cyclophosphamide. Whether this approach is superior to pulse intravenous cyclophosphamide is yet to be determined. Two other approaches to treatment were also reported: anti-CD4, based on success in case reports, merits further study; the modified androgen, 19-nortestosterone, was unfortunately not effective. Other case reports provide additional evidence for specific treatments in certain situations, such as the use of tetracycline pleurodesis for recurrent pleural effusions. Finally, reports of new side effects for old medicines and new ones are a reminder that the treatment can be part of the problem when a lupus patient develops complications.

Bronchiolitis Obliterans↗
PubMed1991

The challenge of caring for indigent children with rheumatologic diseases.

Poverty and lack of insurance prevent complete access to tertiary care for many children with rheumatologic diseases. Long-term solutions to provide community based support for local teams and other services are needed. Physicians need to work with colleagues in health care systems and government to make the health care system fully available to all families. Medical schools can act as catalysts in helping government agencies redefine policies to support outreach and other health care programs for the indigent. Governmental agencies must collaborate with insurance companies to change policies so as to cover all aspects of service, including those provided by arthritis health professionals. With coordinated effort, the goal of adequate services to indigent children with rheumatologic and other chronic illnesses can become reality.

Adolescent↗