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Biomedical subjects

A J Smith

Publications and source records attributed to A J Smith.

At least 91 records · Page 5Linked to original sources
PubMed2001

Use of chlorine dioxide to disinfect dental unit waterlines.

This paper describes a trial of chlorine dioxide in dental unit waterlines to produce potable quality water. Four treatment protocols using 50 ppm activated chlorine dioxide solution were tested. Each caused a short-term (<48 h) decline in total viable counts but did not provide potable quality water. Intermittent use of chloride dioxide is thus not suitable for long-term decontamination of dental unit waterlines. Units should be redesigned to discourage biofilm formation, and more research into practical methods of achieving potable water is required in the interim.

Chlorine Compounds↗
PubMed2001

Performance of standard and reservoir-type Hudson masks in pregnant and non-pregnant subjects.

We have assessed the performance of the Hudson-type mask without reservoir and the Hudson non-rebreathing mask with reservoir bag in 10 pregnant and 10 non-pregnant women at different oxygen flow rates by measuring end-expired oxygen fraction (FEO(2)). The Hudson mask without reservoir behaved similarly in pregnant and non-pregnant women, providing a mean FEO(2) of 0.32 with oxygen flow of 4 L.min(-1) which increased to 0.46 at 15 L.min(-1). The reservoir mask produced a lower FEO(2) in pregnant subjects than in non-pregnant subjects, with a mean FEO(2) of 0.33 and 0.64 at 4 L.min(-1) and 15 L.min(-1) in pregnant subjects compared to 0.44 and 0.72, respectively, in non-pregnant women. Neither mask delivers the expected maximum inspired oxygen fraction quoted by its manufacturer, assuming that inspired oxygen fraction quoted by its manufacturer, assuming that inspired oxygen fraction is 0.06 higher than expired and correcting for humidification of inhaled gases within the respiratory tract. The importance of these findings in the care of the obstetric patient and the treatment of acute fetal hypoxia is discussed.

Journal Article↗
PubMed2001

Plant sterols regulate rat vascular smooth muscle cell growth and prostacyclin release in culture.

Cardiovascular disease (CVD) is the leading cause of death in the USA and other industrialized countries. A large number of epidemiological studies have established a direct correlation between diet and the development and progression of atherosclerosis. Several studies have shown the incidence of CVD to be lower in populations consuming a predominantly plant-based diet, as compared to meat-based diets. Besides being low in fat and cholesterol, vegetarian and Asian diets contain a large variety of phytochemicals, which may function in the body. For example, phytosterols (PS) are plant sterols that interfere with the absorption of cholesterol from the intestine when present in adequate amounts. Although PS may also function at a cellular level in the body, there are few studies examining the action of PS on cells involved in atherosclerosis. The purpose of this study was to examine the effect of dietary PS on vascular smooth muscle cell (VSMC) growth and function, since VSMC play a central role in the development of atherosclerosis. VSMC were treated with 16 microM cholesterol, 25-hydroxycholesterol, campesterol and beta-sitosterol (SIT) using an ethanol as a vehicle. Cell growth was determined by cell counting and cell proliferation by DNA synthesis, which was measured by [(3)H]-thymidine incorporation. Cholesterol supplementation had no effect on cell growth and proliferation. 25-Hydroxycholesterol decreased cell growth by 68% and DNA synthesis by 99%. SIT was found to inhibit VSMC growth more effectively than campesterol. Of the two PS, campesterol decreased cell growth by 16% and SIT decreased cell growth by 30%. DNA synthesis was decreased 25% by SIT supplementation but was not influenced by campesterol or cholesterol supplementation. Cholesterol, campesterol and SIT were not cytotoxic to VSMC and did not significantly alter cell viability. 25-Hydroxycholesterol, however, was cytotoxic and decreased cell viability by 45% as determined by lactate dehydrogenase release and a trypan blue dye exclusion test. De novo cholesterol synthesis was decreased 28% by campesterol, 49% by SIT and 23% by cholesterol. Beta-sitosterol exhibited a greater effect on cholesterol synthesis than campesterol or cholesterol supplementation. Measurement of cell sterol content demonstrated incorporation of PS into VSMC at the expense of cholesterol. Campesterol decreased VSMC cholesterol content by 36%, representing 40% of the total sterol content following treatment. Beta-sitosterol decreased VSMC cholesterol by 41% following supplementation and represented 49% of the total sterol amount. Cholesterol treatment did not alter the cholesterol content of the cells. Prostacyclin production was significantly altered by PS treatment. Basal prostacyclin release was increased 43% by campesterol and 81% by SIT. A23187 stimulated prostacyclin release was increased 25% by campesterol and 54% by SIT. SIT supplementation induced a greater effect on prostacyclin release from VSMC than cholesterol or campesterol supplementation. The in vitro results presented here suggest that dietary PS, especially SIT, may offer protection from the VSMC hyperproliferation found in atherosclerosis. Further in vivo research is needed to support these observations.

Animals↗
PubMed2001

Management of persistent or locally recurrent epidermoid cancer of the anal canal with abdominoperineal resection.

We retrospectively evaluated the outcome of 22 patients with epidermoid cancer of the anal canal who underwent surgical salvage after failure of primary chemoradiotherapy. Patients who required surgery had significantly more advanced T-stage than those who did not fail chemoradiotherapy. Eighteen patients failed surgical salvage. Invasion through the muscle wall of the bowel was present in 16 of 18 patients compared with two of four patients who have no evidence of disease (follow-up 5-10 years). Failure occurred only in the pelvis in 13 of the patients who died of disease. The mean time to death after surgery was 19 months. We confirm the overall poor results of conventional abdominoperineal resection in those patients who have failed previous therapy. Most failures occur in the pelvis. Transanorectal ultrasound and magnetic resonance imaging (MRI) may allow better selection of patients for exenterative procedures and identify those not amenable to successful salvage.

Abdomen↗
PubMed2001

Topical tacrolimus in the management of peristomal pyoderma gangrenosum.

BACKGROUND: Peristomal pyoderma gangrenosum (PPG) is a potentially disabling disease in stoma patients. Topical tacrolimus has been shown to be effective in the management of pyoderma gangrenosum. Unfortunately, greasy topical treatments may be impractical for PPG because of impaired appliance adhesion. OBJECTIVE: The purpose of this open study was to evaluate the therapeutic effectiveness of topical tacrolimus 0.3% formulated in carmellose sodium paste compared with topical corticosteroid preparations in the management of PPG. RESULTS: A total of 11 patients with PPG received treatment with topical tacrolimus 0.3% in Orabase trade mark and 13 with topical clobetasol propionate 0.05% as monotherapy in each case. Seven of the tacrolimus-treated group healed completely (mean time to healing: 5.1 weeks) compared with five of the clobetasol propionate-treated group (mean time to healing: 6.5 weeks). Topical tacrolimus was significantly more effective than clobetasol propionate in managing larger PPG lesions (ulcer diameter > 2 cm). In six patients, who had failed to respond adequately to multiple systemic and topical treatments for PPG, the addition of topical tacrolimus was associated with healing of PPG within 6 weeks. CONCLUSION: These results suggest that topical tacrolimus 0.3% in Orabase trade mark is a more effective and expeditious treatment than clobetasol propionate 0.05% for PPG. It is significantly more effective than clobetasol propionate 0.05% in managing lesions larger than 2 cm in diameter. Topical tacrolimus may be highly effective when other systemic or topical treatments have been unsuccessful.

Abdomen↗
PubMed2001

The ecology of Staphylococcus species in the oral cavity.

Whilst the diversity of organisms present in the oral cavity is well accepted, there remains considerable controversy as to whether Staphylococcus spp. play a role in the ecology of the normal oral flora. Surprisingly little detailed work has been performed on the quantitative and qualitative aspects of colonisation or infection either by coagulase-negative staphylococci (CNS) or S. aureus. The latter is especially interesting in the light of present difficulties in eradicating carriage of methicillin-resistant S. aureus (MRSA) from the oropharynx in affected individuals. This paper reviews the current knowledge of staphylococcal colonisation and infection of the oral cavity in health and disease. S. aureus has been isolated from a wide range of infective oral conditions, such as angular cheilitis and parotitis. More recently, a clinical condition classified as staphylococcal mucositis has emerged as a clinical problem in many debilitated elderly patients and those with oral Crohn's disease. Higher carriage rates of both CNS or S. aureus, or both, in patients prone to joint infections raises the interesting possibility of the oral cavity serving as a potential source for bacteraemic spread to compromised joint spaces. In conclusion, there is a surprising paucity of knowledge regarding the role of oral staphylococci in both health and disease. Further work in this area may lead to benefits, such as improved decolonisation regimens for eradication of MRSA and acknowledgement of the mouth as a source of bacteraemic staphylococci.

Ecosystem↗
PubMed2001

Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux.

Inhibitory gamma-aminobutyric acid (GABA)(A) receptors are subject to modulation at a variety of allosteric sites, with pharmacology dependent on receptor subunit combination. The influence of different alpha subunits in combination with beta3gamma2s was examined in stably expressed human recombinant GABA(A) receptors by measuring (36)Cl influx through the ion channel pore. Muscimol and GABA exhibited similar maximal efficacy at each receptor subtype, although muscimol was more potent, with responses blocked by picrotoxin and bicuculline. Receptors containing the alpha3 subunit exhibited slightly lower potency. The comparative pharmacology of a range of benzodiazepine site ligands was examined, revealing a range of intrinsic efficacies at different receptor subtypes. Of the diazepam-sensitive GABA(A) receptors (alpha1, alpha2, alpha3, alpha5), alpha5 showed the most divergence, being discriminated by zolpidem in terms of very low affinity, and CL218,872 and CGS9895 with different efficacies. Benzodiazepine potentiation at alpha3beta3gamma2s with nonselective agonist chlordiazepoxide was greater than at alpha1, alpha2, or alpha5 (P < 0.001). The presence of an alpha4 subunit conferred a unique pharmacological profile. The partial agonist bretazenil was the most efficacious benzodiazepine, despite lower alpha4 affinity, and FG8205 displayed similar efficacy. Most striking were the lack of affinity/efficacy for classical benzodiazepines and the relatively high efficacy of Ro15-1788 (53 +/- 12%), CGS8216 (56 +/- 6%), CGS9895 (65 +/- 6%), and the weak partial inverse agonist Ro15-4513 (87 +/- 5%). Each receptor subtype was modulated by pentobarbital, loreclezole, and 5alpha-pregnan-3alpha-ol-20-one, but the type of alpha subunit influenced the level of potentiation. The maximal pentobarbital response was significantly greater at alpha4beta3gamma2s (226 +/- 10% increase in the EC(20) response to GABA) than any other modulator. The rank order of potentiation for pregnanolone was alpha5 > alpha2 > alpha3 = alpha4 > alpha1, for loreclezole alpha1 = alpha2 = alpha3 > alpha5 > alpha4, and for pentobarbital alpha4 = alpha5 = alpha2 > alpha1 = alpha3.

Allosteric Regulation↗
PubMed2001

Role of beta-dystrobrevin in nonmuscle dystrophin-associated protein complex-like complexes in kidney and liver.

beta-Dystrobrevin is a dystrophin-related and -associated protein that is highly expressed in brain, kidney, and liver. Recent studies with the kidneys of the mdx3Cv mouse, which lacks all dystrophin isoforms, suggest that beta-dystrobrevin, and not the dystrophin isoforms, may be the key component in the assembly of complexes similar to the muscle dystrophin-associated protein complexes (DPC) in nonmuscle tissues. To understand the role of beta-dystrobrevin in the function of nonmuscle tissues, we generated beta-dystrobrevin-deficient (dtnb(-/-)) mice by gene targeting. dtnb(-/-) mice are healthy, fertile, and normal in appearance. No beta-dystrobrevin was detected in these mice by Western blotting or immunocytochemistry. In addition, the levels of several beta-dystrobrevin-interacting proteins, namely Dp71 isoforms and the syntrophins, were greatly reduced from the basal membranes of kidney tubules and liver sinusoids and on Western blots of crude kidney and liver microsomes of beta-dystrobrevin-deficient mice. However, no abnormality was detected in the ultrastructure of membranes of kidney and liver cells or in the renal function of these mice. beta-Dystrobrevin may therefore be an anchor or scaffold for Dp71 and syntrophin isoforms, as well as other associating proteins at the basal membranes of kidney and liver, but is not necessary for the normal function of these mice.

Alleles↗
PubMed2001

Trans-dentinal stimulation of tertiary dentinogenesis.

Trans-dentinal stimulation of tertiary dentinogenesis has long been recognized, and has traditionally been ascribed to diffusion of irritant substances arising during injury and restorative treatment. Identification of bio-active components, especially growth factors including TGF-beta s, sequestered within dentin matrix provides a new explanation for cellular signaling during tertiary dentinogenesis. Both isolated dentin matrix components and pure growth factors (TGF-beta s) have been shown to signal cellular events leading to reactionary and reparative tertiary dentinogenesis. Release of these bio-active components from dentin matrix may arise during carious attack and other injury to the tissue, and also during subsequent surgical intervention and restoration of the tooth. Both cavity-conditioning agents and leaching from restorative materials may contribute to release of these components. Distance of diffusion, as determined by cavity residual dentin thickness, and other restorative parameters may influence the signaling process after release of these components. Careful consideration of the interplay between tissue injury and surgical and restorative material factors is required for optimum exploitation of the exquisite regenerative capacity of dentin-pulp for more biological approaches to clinical treatment of dental disease.

Animals↗
PubMed2001

Expression of TGF-beta receptors I and II in the human dental pulp by in situ hybridization.

Members of the TGF-beta family of growth factors are important in modulation of odontoblast secretory activity during dental tissue repair. Odontoblast expression of TGF-beta isoforms during development leads to their sequestration within the dentin matrix, from where they may be released during carious injury and participate in reparative processes. Two receptors, implicated in TGF-beta-mediated cell signaling, have been identified immunohistochemically in both odontoblasts and pulpal cells of healthy and carious human molar teeth. This study aimed to characterize the expression of the TGF-beta receptors I and II in sound and carious teeth by means of in situ hybridization, to help our understanding of the response of these cells to TGF-beta stimulation. Sound and carious human third molar teeth were routinely processed immediately following extraction, and 10-microns paraffin-embedded sections prepared. These sections were hybridized with 32P-labeled probes to TGF-beta receptors I and II, and the subsequent signal was detected by autoradiography. mRNA for both receptors I and II was mainly detected within the odontoblasts and nerve-associated cells of healthy tissues, with expression at lower levels seen within the subodontoblast and pulp core cells. The expression in odontoblasts was higher for TGF-beta receptor I than for receptor II. Expression of both receptors was more homogenous in all pulp cells within carious teeth, because of an increase of signal within the underlying pulp cell population, including blood-vessel-associated cells. We conclude that the TGF-beta receptors I and II were expressed in odontoblasts and pulp cells, and that subtle variations in the levels of their expression could be involved in the tissue response to injury.

Activin Receptors, Type I↗
PubMed2001

Induction and regulation of crown dentinogenesis: embryonic events as a template for dental tissue repair?

Close regulation of odontoblast differentiation and subsequent secretory activity is critical for dentinogenesis during both embryogenesis and tissue repair. Some dental papilla cells achieve commitment and specific competence, allowing them to respond to epithelially derived inductive signals during the process of odontoblast differentiation. Temporo-spatial regulation of odontoblast differentiation is dependent on matrix-mediated interactions involving the basement membrane (BM). Experimental studies have highlighted the possible roles of growth factors in these processes. Regulation of functional activity of odontoblasts allows for both ordered secretion of the primary dentin matrix and maintenance of vitality and down-regulation of secretory activity throughout secondary dentinogenesis. After injury to the mature tooth, the fate of the odontoblast can vary according to the intensity of the injury. Milder injury can result in up-regulation of functional activity leading to focal secretion of a reactionary dentin matrix, while greater injury can lead to odontoblast cell death. Induction of differentiation of a new generation of odontoblast-like cells can then lead to reparative dentinogenesis. Many similarities exist between development and repair, including matrix-mediation of the cellular processes and the apparent involvement of growth factors as signaling molecules despite the absence of epithelium during repair. While some of the molecular mediators appear to be common to these processes, the close regulation of primary dentinogenesis may be less ordered during tertiary dentinogenic responses.

Basement Membrane↗
PubMed2001

Restorative pulpal and repair responses.

BACKGROUND: Each year, about 90 million new restorations are placed in the United States and 200 million are replaced. Controversy surrounds the pulpal reactions and frequency of bacterial microleakage associated with common restorative materials. The authors investigated and compared pulpal reactions to different types of restorative materials. METHODS: Two hundred seventy-two teeth with standardized rectangular Class V unexposed cavities were restored with resin-based composite bonded to dentin; resin-based composite bonded to enamel; resin-modified glass ionomers, or RMGI; amalgam lined with zinc polycarboxylate, or ZnPC; amalgam lined with calcium hydroxide, or Ca(OH)2; or zinc oxide-eugenol, or ZnOE. Teeth were extracted for orthodontic reasons between 20 and 381 days later. The authors categorized pulpal responses according to standards set by the Federation Dentaire Internationale and the International Organization for Standardization. Bacteria were detected using Brown-Brenn-stained sections. Pulpal responses were evaluated using histomorphometric analysis and analysis of variance statistics. RESULTS: The results showed that RMGI was the best material for preventing bacterial microleakage, and resin-based composite bonded to enamel was the worst. In regard to minimizing pulpal inflammatory activity, ZnOE was the best material and resin-based composite bonded to enamel was the worst. In terms of maximizing odontoblast survival beneath deep cavity preparations, Ca(OH)2, was the best material and RMGI was the worst. CONCLUSIONS: The results show that bacterial microleakage, pulpal injury and repair responses varied widely with different restorative materials. CLINICAL IMPLICATIONS: The authors recommend that RMGI be used to restore teeth with cavities that are shallow to moderate in depth, with the floor of deep cavities being lined with Ca(OH)2 before the teeth are restored with RMGI.

Adolescent↗
PubMed2000

Characterisation of inhibitory and excitatory postsynaptic currents of the rat medial superior olive.

The medial superior olive (MSO) is part of the binaural auditory pathway, receiving excitatory projections from both cochlear nuclei and an inhibitory input from the ipsilateral medial nucleus of the trapezoid body (MNTB). We characterised the excitatory and inhibitory synaptic currents of MSO neurones in 3- to 14-day-old rats using whole-cell patch-clamp methods in a brain slice preparation.A dual component EPSC was mediated by AMPA and NMDA receptors. The AMPA receptor-mediated EPSC decayed with a time constant of 1.99+/-0.16 ms (n = 8). Following blockade of glutamate receptors, a monosynaptic strychnine-sensitive response was evoked on stimulation of the MNTB, indicative of a glycine receptor-mediated IPSC. GABAA receptors contributed to IPSCs in rats under 6 days old (bicuculline blocked 30% of the IPSC). In older rats little or no bicuculline-sensitive component was detectable, except in the presence of flunitrazepam. These glycinergic IPSCs showed a reversal potential that varied with changes in [Cl-]i, as predicted by the Nernst equation. The IPSC exhibited two developmentally relevant changes. (i) At around postnatal day 6, the GABAA receptor-mediated component declined, leaving a predominant glycine-mediated IPSC. The isolated glycinergic IPSC decayed with time constants of 7.8+/-0.3 and 38.3+/-1.7 ms, with the slower component contributing 7.8+/-0.6% of the peak amplitude (n = 121, 3-11 days old, -70 mV, 25 deg C). (ii) After day 11 the IPSC fast decay accelerated to 3.9+/-0.3 ms (n = 12) and the magnitude of the slow component declined to less than 1%. Spontaneous miniature glycinergic IPSCs (mIPSCs) were variable in amplitude and were of large conductance (1.83+/-0.19 nS, n = 8). The amplitude was unchanged on lowering [Ca2+]o. The time course of evoked and spontaneous miniature glycinergic IPSCs were compared. The 10-90% rise times were 0.7 and 0.6 ms, respectively. The evoked IPSC decayed with a fast time constant of 7.2+/-0.7 ms, while the mIPSC decayed with a fast time constant of 5.3+/-0.4 ms in the same seven cells.The glycinergic IPSC decay was voltage dependent with an e-fold change over 118 mV. The temperature dependence of the IPSC decay indicated a Q10 value of 2. Picrotoxin and cyanotriphenylborate had little or no effect on IPSCs from 6- to 14-day-old animals, implying homomeric channels are rare. We conclude that the MSO receives excitatory inputs mediated by AMPA and NMDA receptors and a strong glycinergic IPSC which has a significant contribution from GABAA receptors in neonatal rats. Functionally, the IPSC could increase membrane conductance during the decay of binaural glutamatergic EPSCs, thus refining coincidence detection and interaural timing differences.

Animals↗
PubMed2000

The T cell oncogene Tal2 is necessary for normal development of the mouse brain.

Transcription factors are commonly involved in leukemia by activation through chromosomal translocations and normally function in cell type(s) that differ from that of the tumor. TAL2 is a member of a basic helix-loop-helix gene family specifically involved in T cell leukemogenesis. Null mutations of Tal2 have been made in mice to determine its function during development. Tal2 null mutant mice show no obvious defects of hematopoiesis. During embryogenesis, Tal2 expression is restricted to the developing midbrain, dorsal diencephalon, and rostroventral diencephalic/telencephalic boundary, partly along presumptive developing fiber tracts. The null mutant mice are viable at birth but growth become progressively retarded and they do not survive to reproductive age. Tal2-deficient mice show a distinct dysgenesis of the midbrain tectum. Due to loss of superficial gray and optical layers, the superior colliculus is reduced in size and the inferior colliculus is abnormally rounded and protruding. Death is most likely due to progressive hydrocephalus which appears to be caused by obstruction of the foramen of Monro (the connection between the ventricles of the forebrain). Thus, in addition to its oncogenicity when ectopically expressed, Tal2 normally plays a pivotal role in brain development and without this gene, mice cannot survive to maturity.

Animals↗
PubMed2000

Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors.

ATP activates damage-sensing neurons (nociceptors) and can evoke a sensation of pain. The ATP receptor P2X3 is selectively expressed by nociceptors and is one of seven ATP-gated, cation-selective ion channels. Here we demonstrate that ablation of the P2X3 gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion neurons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X(2/3) heteromultimers. Null mutants have normal sensorimotor function. Behavioural responses to noxious mechanical and thermal stimuli are also normal, although formalin-induced pain behaviour is reduced. In contrast, deletion of the P2X3 receptor causes enhanced thermal hyperalgesia in chronic inflammation. Notably, although dorsal-horn neuronal responses to mechanical and noxious heat application are normal, P2X3-null mice are unable to code the intensity of non-noxious 'warming' stimuli.

Adenosine Triphosphate↗