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Biomedical subjects

H Fong

Publications and source records attributed to H Fong.

At least 19 recordsLinked to original sources

Controlled failure mechanisms toughen the dentino-enamel junction zone.

STATEMENT OF PROBLEM: The dentino-enamel junction (DEJ) durably unites dissimilar hard brittle enamel and tough flexible dentin. In contrast to artificial bonds between restorations and dentin, the DEJ rarely fails except when it is affected by inherited disorders. Knowledge of DEJ toughening mechanisms is important in understanding inherited disorders, in biomimetic engineering of junctions between artificial restorations and teeth, and in tissue-engineering a DEJ. PURPOSE: The purpose of this study was to identify specific DEJ-zone failure mechanisms and to survey the fracture toughness of the human DEJ zone. MATERIAL AND METHODS: Fracture toughness indentations were made at 3 sites across the DEJ zone of 10 human incisor teeth. Failure modes identified using optical microscopy and fracture toughness (MPa.m(1/2)) were calculated following Vickers microindentation. Site mean values were then calculated and compared using 1-way analysis of variance (alpha=.05). RESULTS: The DEJ did not undergo catastrophic interfacial delamination; instead, damage was distributed over a broad zone. The primary damage mode involved cracking and damage dispersion in the specialized first-formed enamel close to the DEJ. Multiple, somewhat convoluted and sometimes branching, cracks spread and diffused damage over a wide area of adjacent enamel rather than producing catastrophic interfacial failure. Other secondary mechanisms included short microcracks in the DEJ adjacent dentin with possible cracked bridging, as well as plastic deformation of the DEJ without delamination. A DEJ-zone fracture toughness of approximately 0.8 to 0.9 MPa.m(1/2) was calculated. CONCLUSION: DEJ-zone damage occurred primarily within the adjacent layer of specialized first-formed enamel, and the optical DEJ interface resisted delamination.

Biomechanical Phenomena↗

Defining the roots of cementum formation.

Significant progress has been seen in research aimed at regeneration of the disease-damaged periodontium. Our own strategy has been to approach periodontal tissue development (i.e. root, cementum, periodontal ligament, and bone) as a source for the identification of key regulators of cellular processes that may be applicable to periodontal tissue repair. Specifically, enamel-like molecules, bone morphogenetic proteins (BMPs), and phosphates have been investigated for their role in altering gene expression and cell functions in follicle cells, periodontal ligament cells, and cementoblasts. Amelogenin, leucine-rich amelogenin peptide, and tyrosine-rich amelogenin peptide have been found to similarly affect cementoblast gene expression and cementoblast-mediated mineralization in vitro; however, these enamel-like factors do not increase cell proliferation as has been observed in cells treated with Emdogain (Biora AB, Malmö, Sweden), an enamel matrix derivative. BMP-2 has been found to promote differentiation of follicle cells into a cementoblast/osteoblast phenotype, and BMP-3 is being investigated as a negative regulator of mineralization. The increased ratio of phosphate to pyrophosphate in the local region during root development has been found to significantly enhance the extent of cementum formation in animal models. Furthermore, phosphate has been identified as a regulator of cementoblast SIBLING (small integrin-binding ligand N-linked glycoprotein) gene expression in vitro. These investigations of candidate factors for periodontal regeneration have uncovered mechanisms regulating gene expression and cell function in cells controlling the behavior of periodontal tissues (i.e. follicle cells, periodontal cells, and cementoblasts) and offer new directions to consider for clinical repair of periodontal defects.

Animals↗

A preliminary RAPD-PCR analysis of Cimicifuga species and other botanicals used for women's health.

Traditional taxonomic methods of botanical identification that rely primarily on morphological observations cannot be used efficiently when only powdered plant materials are available. Thus, our objectives were to determine if we could apply a molecular approach to: a) produce unique DNA profiles that are characteristic of the species, and b) determine if the geographical area or time of collection influences these DNA profiles. Towards this end, random amplified polymorphic DNA (RAPD) analyses were performed on a number of botanicals currently used for women's health. The test materials included samples from three species each of the genera Cimicifuga (Actaea) and Trifolium, as well as samples of Vitex agnus-castus L., Glycyrrhiza glabra L., Gingko biloba L., Valeriana officinalis L., Angelica sinensis (Oliv.) Diels, Viburnum prunifolium L., Humulus lupulus L., Vaccinium macrocarpon Ait., Panax ginseng C.A. Mey. Cimicifuga racemosa (L.) Nutt. and Trifolium pratense L. are currently under clinical investigation in our basic research laboratories and medical clinic for the relief of post-menopausal symptoms. Characteristic profiles produced with the OPC-15 primer could distinguish the three Cimicifuga species: C. racemosa, C. americana and C. rubifolia. Similar results were obtained with the three Trifolium species: Trifolium pratense L., Trifolium incarnatum L., and Trifolium repens L. Accessions of cultivated T. pratense collected from the same field at different times, produced identical profiles. Accessions of Cimicifuga species collected from different geographical areas produced similar but not identical DNA profiles; however, species-specific DNA fragments were identified. These results demonstrate that RAPD analysis can be applied to distinguish species when only powdered material is available for testing. This methodology can be applied to identify species of commercial value regardless of collection time or geographic area.

Cimicifuga↗

Expression pattern of the Rett syndrome gene MeCP2 in primate prefrontal cortex.

Dysfunction of the prefrontal cortex may contribute to the autistic features and mental retardation of Rett syndrome, a neuropsychiatric condition caused by mutations of the gene encoding methyl-CpG-binding protein 2 (MeCP2). Because nothing is known about the expression of MeCP2 and other chromatin-associated factors in primate brain, we studied in monkey prefrontal cortex and murine cerebral cortex expression patterns of MeCP2 and of macrohistone H2A (MacroH2A), which like MeCP2 is associated with transcriptionally silent chromatin. In both species, MeCP2 and MacroH2A appeared to be ubiquitously expressed by cortical neurons, including projection neurons and GABAergic interneurons. In the adult monkey, MeCP2 expression was robust throughout all layers of the prefrontal cortex but it was limited in fetal monkeys at embryonic day 110 to the deeper cortical layers and the subplate. These results suggest that MeCP2 may be important for neuronal maintenance in the developing and in the mature primate prefrontal cortex, consistent with the previously reported phenotype of MeCP2-null mutant mice.

Age Factors↗

Regulated gene expression dictates enamel structure and tooth function.

Enamel is a complex bioceramic tissue. In its final form, enamel is a reflection of the unique molecular and cellular activities occurring during organogenesis. From the ectodermal origins of ameloblasts, their gene activity and protein expression profiles exist for the sole purpose of producing a mineralized shell, almost entirely devoid of protein, deposited over the 'bone-like' dentine. The interface between enamel and dentine is referred to as the dentine enamel junction and it is also unique in its biology. This review article is narrow in its scope. We restrict our review to selected advances in our understanding of the genetic, molecular and structural aspects of enamel biology. We present a model of enamel formation that relates gene expression to the assembly of an extracellular protein matrix that in turn controls the structural hierarchy and mechanical aspects of enamel and the tooth organ.

Amelogenin↗

Biological organization of hydroxyapatite crystallites into a fibrous continuum toughens and controls anisotropy in human enamel.

Enamel forms the outer surface of teeth, which are of complex shape and are loaded in a multitude of ways during function. Enamel has previously been assumed to be formed from discrete rods and to be markedly aniostropic, but marked anisotropy might be expected to lead to frequent fracture. Since frequent fracture is not observed, we measured enamel organization using histology, imaging, and fracture mechanics modalities, and compared enamel with crystalline hydroxyapatite (Hap), its major component. Enamel was approximately three times tougher than geologic Hap, demonstrating the critical importance of biological manufacturing. Only modest levels of enamel anisotropy were discerned; rather, our measurements suggest that enamel is a composite ceramic with the crystallites oriented in a complex three-dimensional continuum. Geologic apatite crystals are much harder than enamel, suggesting that inclusion of biological contaminants, such as protein, influences the properties of enamel. Based on our findings, we propose a new structural model.

Anisotropy↗

Red cell ferritin and iron overload in heterozygous beta-thalassemia.

Red cell ferritin was evaluated in 101 individuals with heterozygous beta-thalassemia to determine its clinical utility as an index for iron deficiency or overload in these subjects. The mean red cell ferritin for the total population was elevated threefold and showed a significant correlation with transferrin saturation, plasma ferritin, and HbA2 levels. Five of six subjects with reduced red cell ferritin had associated iron deficiency; a further five had iron deficiency and normal red cell ferritin. Normal red cell ferritin occurred in 51 subjects, and 44 had increased values. In the elevated red cell ferritin group, 21 individuals had associated normal plasma ferritin, and 23 had increased plasma ferritin. Only in the latter group was red cell ferritin significantly correlated with transferrin saturation and plasma ferritin. Ten individuals had a red cell ferritin greater than or equal to 150 attogram/cell, and liver biopsy performed in four showed grades II to IV iron overload. A clinical feature of subjects with both increased red cell and plasma ferritin levels was a high incidence of inappropriate iron administration. These findings suggest that red cell ferritin, particularly when combined with plasma ferritin, is a useful parameter for determining potential iron overload in individuals with heterozygous beta-thalassemia.

Adolescent↗

Transplantation in Manitoba.

1. Renal transplantation can be performed at small regional centers as successfully as at large centers. 2. Immunosuppression should be individualized for the patient thereby avoiding the use of costly and often clinically complicated immunosuppressive regimens. 3. Small centers need to participate in large regional pools in order to give highly presensitized patients a reasonable chance of successful transplantation. 4. Long-term patient compliance is a major problem and requires careful surveillance of patients' adherence to their prescribed therapy. Frequent follow-up also allows for the detection of late rejection episodes which can often be reversed.

Graft Survival↗

Low-dose intra-arterial streptokinase infusion therapy of peripheral arterial occlusions and occluded vein grafts.

To study the effectiveness of low-dose thrombolytic therapy the authors report their experience with local, low-dose, intra-arterial streptokinase infused at a rate of 5000 units/h in four patients with occluded vein grafts and eight with peripheral arterial occlusions presenting with limb-threatening ischemia. The patients had had symptoms for 4 hours to 6 weeks. The streptokinase infusion successfully declotted two occluded vein grafts and restored distal blood flow in five patients with peripheral arterial occlusion. Complications resulting in early withdrawal of thrombolytic therapy included surgical wound hematomas in two patients. Two patients had severe bleeding at the arterial puncture site leading to the death of one of them. Treatment after cessation of thrombolytic therapy included femoropopliteal bypass in three patients, percutaneous transluminal balloon dilatation of a stenotic popliteal artery in one patient and thromboembolectomy in three patients. Two patients required below-knee amputation because of irreversible ischemia. The authors conclude that in carefully selected patients, intra-arterial infusion of streptokinase locally in low dosage is an important adjunct in the treatment of limb-threatening ischemia caused by occluded vein grafts and acute arterial thrombosis. They warn that selective thrombolytic therapy with streptokinase must be used with caution since it may be associated with serious complications.

Aged↗

Red cell ferritin content: a re-evaluation of indices for iron deficiency in the anaemia of rheumatoid arthritis.

In iron deficiency anaemia basic red cell content of ferritin is appreciably reduced. This variable was determined in 62 patients with rheumatoid arthritis to evaluate conventional laboratory indices for iron deficiency in the anaemia of rheumatoid arthritis. For 23 patients with rheumatoid arthritis and normocytic anaemia irrespective of plasma ferritin concentration, red cell ferritin content did not differ significantly from that for non-anaemic patients with rheumatoid arthritis. For 27 patients with rheumatoid arthritis and microcytic anaemia, the mean red cell ferritin content for patients with a plasma ferritin concentration in the 13-110 micrograms/l range was appreciably reduced. It was indistinguishable from that for patients with rheumatoid arthritis and classical iron deficiency anaemia, indicated by plasma ferritin concentrations of less than 12 micrograms/l. In contrast, the mean red cell ferritin content for patients with rheumatoid arthritis, microcytic anaemia, and plasma ferritin concentrations above 110 micrograms/l did not differ from that for patients with rheumatoid arthritis and normocytic anaemia. Oral treatment with iron in patients with rheumatoid arthritis, microcytic anaemia, and appreciably reduced red cell ferritin concentrations was accompanied by significant increases in haemoglobin concentration (p less than 0.01), mean corpuscular volume (p less than 0.01), and red cell ferritin contents (p less than 0.05). This treatment, however, did not produce any appreciable change in haemoglobin concentration in patients with rheumatoid arthritis, normocytic anaemia, and normal red cell ferritin contents. These findings suggest that the indices for iron deficiency in patients with rheumatoid arthritis and anaemia should include peripheral blood microcytosis together with a plasma ferritin concentration of less than 110 micrograms/l.

Adolescent↗

Red cell basic ferritin content of patients with megaloblastic anaemia due to vitamin B12 or folate deficiency.

The basic ferritin content of red cells was measured in patients with untreated megaloblastic anaemia. The red cell ferritin of 10 patients with anaemia and vitamin B12 deficiency (mean 579, range 68-2616 attogram (ag)/cell); and of 8 patients with folate deficiency (mean 792, range 141-2373 ag/cell) were significantly elevated (P less than 0.001) compared with normal subjects (mean 10.7, range 4-47 ag/cell) and showed a significant correlation with pre-treatment levels of plasma ferritin and less so with percent transferrin saturation. Following vitamin replacement elevated red cell ferritin levels decreased during the period of reticulocytosis and was normal in 9 patients evaluated after 6 months. The magnitude of increase in red cell basic ferritin levels observed in untreated megaloblastic anaemia is comparable to that of subjects with idiopathic haemochromatosis and suggests that interpretation of this index for iron overload should take into consideration concomitant body folate or vitamin B12 status.

Adult↗

Basic ferritin content of red cells of patients with anemia and polycythemia vera.

Basic ferritin content of red cells has been evaluated with a simplified assay in subjects with various erythroid disorders. In 39 patients with iron deficiency anemia, red cell ferritin was significantly reduced compared with that of normal individuals. Thirty percent of these patients had low normal red cell ferritin content and the MCV for this group was significantly higher than that of patients with reduced red cell ferritin. The mean red cell ferritin of 30 subjects with the anemia of chronic disease was significantly reduced and patients in this group with normal red cell ferritin had higher plasma ferritin levels. In 14 patients with polycythemia vera, the mean red cell ferritin was significantly reduced and showed a positive correlation with the hemoglobin level and percent transferrin saturation. The red cell ferritin content of 9 individuals with acquired immune hemolytic anemia and 10 with acquired sideroblastic anemia was significantly elevated and, in subjects with immune hemolysis, showed a positive correlation with the reticulocyte count. These findings suggest a lack of discriminatory function for red cell ferritin in iron deficiency anemia and anemia of chronic disease. Evaluation of this parameter in the individual patient should take into account the presence of reticulocytosis.

Anemia↗

Erythrocyte ferritin content in idiopathic haemochromatosis and alcoholic liver disease with iron overload.

The erythrocyte ferritin content was measured in patients with either idiopathic haemochromatosis or alcoholic liver disease and iron overload to define its value as a marker for an excess of tissue iron. The mean erythrocyte ferritin content in patients with untreated idiopathic haemochromatosis was increased 60-fold and fell with phlebotomy. After phlebotomy many patients had an increased red cell ferritin content despite normal serum ferritin concentrations. That this reflected persistent iron overload with inadequate phlebotomy was suggested by the higher serum iron concentrations, percentage transferrin saturation, and urinary excretion of iron after administration of desferrioxamine, together with a lower annual iron loss by phlebotomy in this group compared with patients with treated disease and normal red cell ferritin content. The mean erythrocyte ferritin content in patients with alcoholic liver disease and iron overload was increased only sevenfold, and the ratio of erythrocyte to serum ferritin clearly discriminated these patients from those with idiopathic haemochromatosis. The determination of erythrocyte ferritin content is a useful non-invasive test for diagnosing idiopathic haemochromatosis, monitoring the effect of phlebotomy in this disorder, and distinguishing patients with this disorder from those with alcoholic liver disease with iron overload.

Adult↗

Hemodynamic assessment of the aortoiliac segment: a prospective study.

A test for assessing stenosis in the aortoiliac segment is described in which femoral pressure is measured directly by continuous monitoring and an intra-arterial injection of papaverine is used to augment blood flow. This test has been described previously but is not widely used. A prospective study of this test was carried out on 64 patients and the results were compared with those obtained by aortography. The test helped to determine whether an operation on the aortoiliac segment was indicated. Clinical results were assessed. Thirty-two of the 64 patients were found to have significant inflow disease (more than 50% stenosis). They underwent aortic reconstruction with total relief or improvement of symptoms in all cases. Aortography demonstrated an essentially normal aortoiliac segment in 3 of the 32 patients and 16 had only irregular segments with no definite stenosis. The authors conclude that any patient presenting with sufficient indication to warrant reconstructive surgery who has a normal or equivocal angiogram should undergo the papaverine pressure test.

Aorta, Abdominal↗

A simple radiometric assay for methotrexate and other folate antagonists.

A rapid radiometric assay for the folate antagonist MTX, based on the inhibition of chicken liver dihydrofolate reductase activity, has been developed. In the system the inhibition by MTX of the reduction of tritiated FH2 is standardized and used to quantitate this antagonist in plasma of subjects receiving high-dose MTX therapy. The assay permits the detection of plasma MTX levels to 5 X 10(-9)M with a coefficient of variation of 15%. The predominating circulating folate, 5 methyltetrahydrofolate, or the rescue agent leucovorin (5 formyltetrahydrofolate) do not significantly interfere with the assay at concentrations attainable with current rescue programs. Analyses of multiple plasma samples with the present assay show close agreement with the competitive protein-binding assay.

Animals↗