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Biomedical subjects

A Pierce

Publications and source records attributed to A Pierce.

At least 37 records · Page 2Linked to original sources
PubMed1999

The epidemiology of lip cancer: a review of global incidence and aetiology.

Lip cancer (140 ICD-9) is a form of oral cancer that has a distinctive global epidemiology. This review summarises global incidence rates for male and female lip cancer with the aid of cancer atlases. High male lip cancer rates are reported for regions of North America (12.7 per 100 000 per annum), Europe (12.0 per 100 000 per annum) and Oceania (13.5 per 100 000 per annum), while it is virtually unknown in parts of Asia. Factors commonly cited as important in the aetiology of lip cancer include solar radiation, tobacco smoking and viruses. An attempt is made to summarise the evidence for factors that may be important in lip carcinogenesis. While incidence rates are generally stable or falling among males worldwide, they are rising in many female populations. The aetiology of the disease is far from established and much information regarding its pathogenesis is based on anecdotal rather than case-controlled epidemiological evidence. The epidemiology of lip cancer supports the proposal that the lip should be considered as a distinct cancer site, rather than being included with other forms of intraoral cancer.

Asia↗
PubMed1999

[Influence of chemotherapeutants and cytokines on growth and transgene expression of bone marrow cells from MT/p210(bcr-abl) transgenic mice].

The bone marrow cells of CML(chronic myelogenous leukemia) transgenic mice carrying metallothionein(MT) promoter/enhancer, bcr-abl(p210) cDNA and SV40 splicing/poly(A) signal sequences were cultured in liquid and soft agar with hydroxyurea (Hu), 5-fluorouracil(5-Fu), mouse stem cell factor (mSCF) and mouse interleukin-3(mIL-3) independently or combinatively. The cell or colony counting and transgene RT-PCR analysis showed that the proliferation, colony formation and transgene expression of the bone marrow cells were advanced in the combinative culture of mSCF with mIL-3, but they were significantly inhibited in the culture without any growth factors, or with mSCF, mIL-3 and Hu or 5-Fu. These findings suggest that the combinative utilization of chemotherapeutants and cytokines is a potentially effective strategy of the clinical treatment for CML.

Animals↗
PubMed1998

p210 Bcr-Abl expression in a primitive multipotent haematopoietic cell line models the development of chronic myeloid leukaemia.

Chronic myeloid leukaemia (CML) is a clonal disorder of the pluripotent haemopoietic stem cell, the hallmark of which is the constitutively activated Bcr-Abl protein tyrosine kinase. During the initial chronic phase of CML the primitive multipotent leukaemic progenitor cells remain growth factor dependent and are capable of producing terminally differentiated cells. Although the available evidence suggests that Bcr-Abl directly affects signalling pathways involved in controlling the development of primitive haemopoietic progenitors the identification of the specific biological consequences of Bcr-Abl activity in these progenitors has been hampered by the lack of suitable systems modelling CML. By transfecting the multipotent haemopoietic cell line FDCP-Mix with a temperature sensitive mutant of Bcr-Abl we have developed the first working model that mirrors the chronic phase of CML. FDCP-Mix cells expressing Bcr-Abl tyrosine kinase activity remain growth factor dependent and retain their ability to differentiate. Normal neutrophilic cells are formed in response to G-CSF and GM-CSF. In addition, the transfected FDCP-Mix cells grown at the permissive temperature for Bcr-Abl tyrosine kinase activity display enhanced survival and proliferation in low concentrations of growth factor. These findings are consistent with the initial subtle changes seen in CML progenitor cells during the chronic phase and confirm that Bcr-Abl effects are context specific, i.e. they depend on the origin and developmental potential of the transfected cells. This questions the significance of studies in non-haemopoietic and differentiation blocked haemopoietic cells.

Cell Division↗
PubMed1998

An activated protein kinase C alpha gives a differentiation signal for hematopoietic progenitor cells and mimicks macrophage colony-stimulating factor-stimulated signaling events.

Highly enriched, bipotent, hematopoietic granulocyte macrophage colony-forming cells (GM-CFC) require cytokines for their survival, proliferation, and development. GM-CFC will form neutrophils in the presence of the cytokines stem cell factor and granulocyte colony-stimulating factor, whereas macrophage colony-stimulating factor leads to macrophage formation. Previously, we have shown that the commitment to the macrophage lineage is associated with lipid hydrolysis and translocation of protein kinase C alpha (PKCalpha) to the nucleus. Here we have transfected freshly prepared GM-CFC with a constitutively activated form of PKCalpha, namely PKAC, in which the regulatory domain has been truncated. Greater than 95% of the transfected cells showed over a twofold increase in PKCalpha expression with the protein being located primarily within the nucleus. The expression of PKAC caused macrophage development even in the presence of stimuli that normally promote only neutrophilic development. Thus, M-CSF-stimulated translocation of PKCalpha to the nucleus is a signal associated with macrophage development in primary mammalian hematopoietic progenitor cells, and this signal can be mimicked by ectopic PKAC, which is also expressed in the nucleus.

Animals↗
PubMed1998

Lactoferrin is synthesized by mouse brain tissue and its expression is enhanced after MPTP treatment.

The biological role and origin of human lactoferrin (Lf) within the brain in normal and disease processes are as yet uncharted. In this context the origin and expression of brain Lf in normal and MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice were investigated using immunohisto chemistry, PCR amplification and in situ hybridization. Lf immunostaining was observed both on sections of mouse lactating mammary gland, which was used as a positive control, and brains from young, adult and aged mice. Lf immunoreactivity was present in the pituitary gland, the hippocampus and the cortex of mouse brains and to a greater extent in older mice. After reverse transcription, Lf transcripts were also found in these brain sections. Lf distribution and expression in the MPTP-induced parkinsonian mouse model were next investigated. A marked depletion of dopamine and its metabolites: dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxy indole acetic acid (5-HIAA) occurs in the high dose MPTP-treated mice. The level of Lf expression was found to be greatly increased in the same animals but Lf immunoreactivity detected in the same brain region was not found increased in the affected areas.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Pulpal injury: pathology, diagnosis and periodontal reactions.

Diagnosis of pulpal disease can be difficult due to the lack of diagnostic signs and symptoms available to the practitioner. An understanding of the possible underlying pathological processes, combined with an exact assessment of the pain history, and appropriate clinical tests, should aid the practitioner in determining the nature of pulpal inflammation, and differentiating it from dentine sensitivity and cracked teeth. The responses of the pulp to traumatic injury to the periodontal membrane (PDM) require special consideration, particularly with respect to the assessment of pulp vitality, and the determination of cases requiring pulp extirpation in order to avoid inflammatory root resorption. Although the pulp is relatively isolated from the rest of the dentoalveolar complex by a dentine/cementum barrier, it is important to remember that it can communicate with the PDM through apical and lateral foramina, and areas of damaged cementum. Hence, it is a priority to both preserve the integrity of the cemental layer in cases of traumatic injury and periodontal disease, and to prevent the inflammation and resorption associated with periapical lesions by accurate diagnosis of irreversible pulpitis and pulp necrosis, followed by appropriate endodontic debridement procedures.

Cracked Tooth Syndrome↗
PubMed1998

Ectopic interleukin-5 receptor expression promotes proliferation without development in a multipotent hematopoietic cell line.

The interleukin-5 (IL-5) receptor is a heterodimer that consists of an IL-5 specific alpha subunit and a common ssc chain that is shared with the receptors for granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3). In contrast to IL-5, which acts mainly as an eosinophil lineage specific factor in vivo, IL-3 and GM-CSF stimulate the survival, proliferation and development of various hematopoietic cell lineages and also multipotent progenitor cells. IL-5 has little effect on the survival or proliferation of the multipotent stem cell line FDCP-Mix A4 but does promote some eosinophil development. To investigate whether the lineage specificity of IL-5 is due to the restricted expression of the IL-5 receptor alpha subunit we transfected the FDCP-Mix A4 cells with a retroviral vector containing this alpha subunit. The ectopic expression of the IL-5 receptor alpha subunit in the FDCP-Mix cells did not increase the observed eosinophilic development but did stimulate survival and proliferation of the transfected cells when IL-5 was added. IL-5 thus acts like IL-3 in these cells, promoting proliferation and survival. The results suggest that IL-5, whilst having a capacity to promote proliferation, does not influence eosinophilic lineage commitment in these multipotent cells. The results further argue that the observed lineage specificity of IL-5 is probably due to factors in addition to the restricted expression of the IL-5 receptor alpha subunit.

Animals↗
PubMed1997

A new function for the LDL receptor: transcytosis of LDL across the blood-brain barrier.

Lipoprotein transport across the blood-brain barrier (BBB) is of critical importance for the delivery of essential lipids to the brain cells. The occurrence of a low density lipoprotein (LDL) receptor on the BBB has recently been demonstrated. To examine further the function of this receptor, we have shown using an in vitro model of the BBB, that in contrast to acetylated LDL, which does not cross the BBB, LDL is specifically transcytosed across the monolayer. The C7 monoclonal antibody, known to interact with the LDL receptor-binding domain, totally blocked the transcytosis of LDL, suggesting that the transcytosis is mediated by the receptor. Furthermore, we have shown that cholesterol-depleted astrocytes upregulate the expression of the LDL receptor at the BBB. Under these conditions, we observed that the LDL transcytosis parallels the increase in the LDL receptor, indicating once more that the LDL is transcytosed by a receptor-mediated mechanism. The nondegradation of the LDL during the transcytosis indicates that the transcytotic pathway in brain capillary endothelial cells is different from the LDL receptor classical pathway. The switch between a recycling receptor to a transcytotic receptor cannot be explained by a modification of the internalization signals of the cytoplasmic domain of the receptor, since we have shown that LDL receptor messengers in growing brain capillary ECs (recycling LDL receptor) or differentiated cells (transcytotic receptor) are 100% identical, but we cannot exclude posttranslational modifications of the cytoplasmic domain, as demonstrated for the polymeric immunoglobulin receptor. Preliminary studies suggest that caveolae are likely to be involved in the potential transport of LDL from the blood to the brain.

Animals↗
PubMed1997

Perception of synthetic /ba/-/wa/ speech continuum by budgerigars (Melopsittacus undulatus).

Other than humans, extensive vocal learning has only been widely demonstrated in birds. Moreover, there are only a handful of avian species that are known to be good mimics of human speech. One such species is the budgerigar (Melopsittacus undulatus), which is a popular mimic of human speech and learns new vocalizations throughout adult life. Using operant conditioning procedures with a repeating background task, we tested budgerigars on the discrimination of tokens from two synthetic /ba/-/wa/ speech continua that differed in syllable, but not transition, duration. Budgerigars showed a significant improvement in discrimination performance on both continua near the phonetic boundary for humans. Budgerigars also showed a shift in the location of the phonetic boundary with a change in syllable length, similar to what has been described for humans and other primates. These results on a nonmammalian species provide support for the operation of a general, nonphonetic, auditory process as one mechanism which can lead to the well-known stimulus-length effect in humans.

Adult↗
PubMed1996

Role of enterobactin and intracellular iron in cell lethality during near-UV irradiation in Escherichia coli.

In Escherichia coli, fur mutants that constitutively express their native iron chelating agent, enterobactin, are significantly more sensitive to near-UV radiation (NUV) than wild type, An entA mutant, which is incapable of synthesizing enterobactin, is equal to wild type in resistance to NUV irradiation. However, the addition of Fe+3 enterobactin but not AI+3 enterobactin to entA cell suspensions just prior to irradiation results in an increased sensitivity to NUV irradiation. A fes mutant, which is unable to reduce and release iron from enterobactin, is significantly more sensitive to NUV irradiation than wild type. The addition of nontoxic levels of H2O2 (5 microM) just prior to irradiation significantly increases sensitivity of both fur and fes mutants. These results suggest that one mechanism by which NUV irradiation leads to cell lethality is by creating a transient iron overload, producing very favorable conditions for the production of highly deleterious free radicals through a variety of mechanisms that lead to oxidative stress and DNA damage including lethal and mutagenic lesions. These results are consistent with the hypothesis that enterobactin is an endogenous chromophore for NUV and contributes to cell lethality via the destruction of its ligand, releasing Fe+2 into the cytoplasm to catalyze the production of highly reactive hydroxyl radicals and other toxic oxygen species via the Haber-Weiss reaction.

Enterobactin↗
PubMed1995

Macrophage inflammatory protein-1 alpha receptors are present on cells enriched for CD34 expression from patients with chronic myeloid leukemia.

The response of normal and chronic myeloid leukemia (CML), CD34+ cells to human macrophage inflammatory protein-1 alpha (MIP-1 alpha or LD78) was assessed. In tritiated thymidine incorporation assays, stem cell factor plus granulocyte-macrophage colony-stimulating factor stimulated thymidine incorporation in normal CD34+ cells was reduced to 72% of control values in the presence of MIP-1 alpha, whereas incorporation by CML CD34+ cells exposed to the same factors was not altered. In clonogenic assays, the presence of MIP-1 alpha gave a level of colony formation that was 71% of control values for normal progenitor cells, whereas for CML CD34+ cells colony formation was enhanced by 25%. These results suggest that, in vitro, CML progenitor cells are relatively refractory to the growth inhibitory effects of MIP-1 alpha. Using flow cytometry, the specific binding of a biotinylated human MIP-1 alpha/avidin fluorescein (FITC) conjugate to normal and CML mononuclear and CD34+ cell populations was quantified. The data indicate that (for both normal and CML CD34+ cells) there was a single population of cells that express cell surface receptors for MIP-1 alpha and this receptor expression was independent of cell cycle status. CML progenitor cells may be refractory to the effects of MIP-1 alpha as a result of events downstream from receptor expression.

Antigens, CD34↗
PubMed1995

Expression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson disease.

The degeneration of nigral dopaminergic neurons in Parkinson disease is believed to be associated with oxidative stress. Since iron levels are increased in the substantia nigra of parkinsonian patients and this metal catalyzes the formation of free radicals, it may be involved in the mechanisms of nerve cell death. The cause of nigral iron increase is not understood. Iron acquisition by neurons may occur from iron-transferrin complexes with a direct interaction with specific membrane receptors, but recent results have shown a low density of transferrin receptors in the substantia nigra. To investigate whether neuronal death in Parkinson disease may be associated with changes in a pathway supplementary to that of transferrin, lactoferrin (lactotransferrin) receptor expression was studied in the mesencephalon. In this report we present evidence from immunohistochemical staining of postmortem human brain tissue that lactoferrin receptors are localized on neurons (perikarya, dendrites, axons), cerebral microvasculature, and, in some cases, glial cells. In parkinsonian patients, lactoferrin receptor immunoreactivity on neurons and microvessels was increased and more pronounced in those regions of the mesencephalon where the loss of dopaminergic neurons is severe. Moreover, in the substantia nigra, the intensity of immunoreactivity on neurons and microvessels was higher for patients with higher nigral dopaminergic loss. These data suggest that lactoferrin receptors on vulnerable neurons may increase intraneuronal iron levels and contribute to the degeneration of nigral dopaminergic neurons in Parkinson disease.

Aged↗
PubMed1995

Rat mammary-gland transferrin: nucleotide sequence, phylogenetic analysis and glycan structure.

The complete cDNA for rat mammary-gland transferrin (Tf) has been sequenced and also the native protein isolated from milk in order to analyse the structure of the main glycan variants present. A lactating-rat mammary-gland cDNA library in lambda gt10 was screened with a partial cDNA copy of rat liver Tf and subsequently rescreened with 5' fragments of the longest clones. This produced a 2275 bp insert coding for an open reading frame of 695 amino acid residues. This includes a 19-amino acid signal sequence and the mature protein containing 676 amino acids and one N-glycosylation site in the C-terminal domain at residue 490. Phylogenetic analysis was carried out using 14 translated Tf nucleotide sequences, and the derived evolutionary tree shows that at least three gene duplication events have occurred during Tf evolution, one of which generated the N- and C-terminal domains and occurred before separation of arthropods and chordates. The two halves of human melanotransferrin are more similar to each other than to any other sequence, which contrasts with the pattern shown by the remaining sequences. Native rat milk Tf is separated into four bands on native PAGE that differ only in their sialic acid content: one biantennary glycan is present containing either no sialic acid residues or up to three. The complete structures of the two major variants were determined by methylation, m.s. and 400 MHz 1H-n.m.r. spectroscopy. They contain either one or two neuraminic acid residues (alpha 2-->6)-linked to galactose in conventional biantennary N-acetyl-lactosamine-type glycans. Most contain fucose (alpha 1-->6)-linked to the terminal non-reducing N-acetylglucosamine.

Animal Population Groups↗
PubMed1995

Human eosinophils express a receptor for secretory component. Role in secretory IgA-dependent activation.

The existence of a functional receptor for secretory component (SC) on the eosinophil membrane might explain the preferential degranulation induced by secretory IgA (sIgA) when compared to serum IgA. Indeed, flow cytometry analysis revealed that purified human SC could bind to a subpopulation (4-59%) of blood eosinophils purified from 19 patients with eosinophilia. Binding of radiolabeled human SC could be competitively inhibited using unlabeled SC or secretory IgA but not with serum IgA or IgG. Immunoprecipitation and immunosorbent chromatography using human SC revealed the presence of a major component at 15 kDa in eosinophil extracts as well as in culture supernatants but not in neutrophils. The 15-kDa protein eluted from the human SC immunosorbent was able to bind to SC or to sIgA but not to serum IgA. Eosinophils preincubated with human SC or sIgA released eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) after addition of anti-SC or anti-IgA monoclonal antibody as respective cross-linking reagents. These results indicated that binding of free or complexed SC to human eosinophils could induce eosinophil degranulation. Furthermore, the dose-dependent inhibition by SC of mediator release induced by sIgA but not by serum IgA, suggested that the receptor for SC could be involved in the preferential degranulation mediated by sIgA. These results indicate a novel pathway of eosinophil activation and its potential involvement in mucosal immunity, particularly in inflammatory diseases associated with infiltration of eosinophils and the enhanced production of sIgA.

Binding, Competitive↗
PubMed1994

Characterization of two kinds of lactotransferrin (lactoferrin) receptors on different target cells.

Lactotransferrin (Lf), an iron-binding glycoprotein present as a major component in the specific granules of human neutrophilic granulocytes is released in the blood during the acute phase of infection and participates in the regulation of the host-defence mechanisms. Our previous observations (Mazurier et al., 1989) showing i) that the activation by PHA of T-lymphocytes induces the appearance at the cell surface of Lf-receptors which are absent from the membrane of resting lymphocytes and ii) that Lf becomes a growth factor for the activated lymphocytes, led us to undertake a series of researches on the presence of Lf receptors at the surface of different blood cells. Characterization of Lf receptors was performed by flow cytofluorimetry using either Lf labelled on its glycan moiety with fluorescein or purified anti-lymphocyte Lf receptor antibodies. High affinity receptors for Lf were characterized only at the surface of human activated lymphocytes and of non-activated platelets. These two receptors possess common physicochemical properties and antigenic epitopes. Low affinity receptors for Lf were characterized on monocytes, eosinophils and neutrophils. These receptors are immunologically different from those found on activated lymphocytes and on non-activated platelets. Cell-lines of human lymphocyte T and megakaryocyte possess lactotransferrin receptors whose properties are similar to those found on peripheral blood cells. The soluble form of the receptor identified in the lymphocytes T culture medium possesses a molecular mass close to that of the membrane receptor suggesting that the cytoplasmic tail of the receptor should be very short.

Blood Platelets↗
PubMed1994

Expression of the lactotransferrin receptor during the differentiation process of the megakaryocyte Dami cell line.

In order to determine whether the human lactotransferrin receptor recently described on platelets was also present on hematopoietic precursors, we investigated its presence and characteristics on the megakaryocytic Dami cell line. The reversible binding of human 5-(([2-(carbo(hydrazino)methyl]thio)acetyl)aminofluorescein-labele d lactotransferrin showed that such a receptor was only present on the subpopulation of the largest cells. The increase in numbers of large cells during culture was paralleled by a concurrent increase in lactotransferrin receptor positive cells. Scatchard analysis of the binding of [125I]-labeled lactotransferrin showed that a single affinity class of binding site was present (Kd = 446 +/- 40 nM) and that there were 52 +/- 3 x 10(5) sites per cell. The mouse monoclonal antibody DP5B3G10, specific for the human lactotransferrin receptor, allowed its characterization as a 105 kDa protein on Western blots. The same monoclonal antibody was used to separate the small and large cell subpopulations of Dami cells by panning. Separate culture of the small cells showed that the receptor appeared prior to and independent from endomitosis. In contrast, GPIb was expressed only by large megakaryocytes. The use of conditioned medium from cultures of whole Dami cell populations indicated that a soluble factor is involved in differentiation, but not in the appearance of the lactotransferrin receptor.

Blood Platelets↗
PubMed1994

Interleukin-2 in neoadjuvant therapy potentiates inhibitory activity of 5-fluorouracil and interferon in experimental liver metastases.

Our previous studies showed that interferon (IFN) used in combination with 5-fluorouracil (5-FU) was effective in inhibiting colorectal tumor cell metastases to the liver in nude mice. Furthermore, IFN was also effective in neoadjuvant therapy and allowed the combination treatment (5-FU + IFN) to be delayed for 2-3 weeks following i.s. injections of tumor cells. In this study, we have examined the potential of interleukin-2 (IL-2) to substitute for IFN in neoadjuvant therapy. IL-2 was found to be equally effective, if not superior, to IFN as a neoadjuvant in inhibiting liver and lung metastases with 5-FU + IFN. Moreover, the effect of IL-2 was demonstrable even after 1 week, whereas IFN did not have an effect until 2 weeks of neoadjuvant dosing. These studies demonstrate IL-2 to be more effective than IFN as an immunomodulatory agent in combination with 5-FU + IFN for the inhibition of liver metastases in nude mice.

Animals↗