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Biomedical subjects

S M Miller

Publications and source records attributed to S M Miller.

At least 19 recordsLinked to original sources
PubMed2006

Broad-spectrum sunscreens prevent the secretion of proinflammatory cytokines in human keratinocytes exposed to ultraviolet A and phototoxic lomefloxacin.

The combination of phototoxic drugs and ultraviolet (UV) radiation can trigger the release of proinflammatory cytokines. The present study measured the ability of sunscreens to prevent cytokine secretion in human keratinocytes following cotreatment of these cells with a known photoreactive drug and UVA. Keratinocytes were treated for 1 h with increasing concentrations of lomefloxacin (LOM) or norfloxacin (NOR), exposed to 15 J/cm2 UVA, and incubated for 24 h. NOR, owing to the absence of a fluorine atom in position 8, was non-phototoxic and used as a negative control. Cell viability and the release of 3 cytokines were assessed, namely interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha). The measurement of these cytokines may be a useful tool for detecting photoreactive compounds. To measure their ability to prevent cytokine secretion, various sunscreens were inserted between the UVA source and the cells. Treatment with NOR, NOR plus UVA, or LOM had no effect on the cells. LOM plus UVA, however, had an effect on cell viability and on cytokine secretion. IL-1alpha levels increased with LOM concentration. The release of TNF-alpha and IL-6 followed the same pattern at lower concentrations of LOM but peaked at 15 micromol/L and decreased at higher concentrations. Sunscreens protected the cells from the effects of LOM plus UVA, as cell viability and levels of cytokines remained the same as in the control cells. In conclusion, the application of broad-spectrum sunscreen by individuals exposed to UVA radiation may prevent phototoxic reactions initiated by drugs such as LOM.

Cell Survival↗
PubMed2004

Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation.

In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose-responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1-4 Gy of (60)Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1-100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small "adapting" stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment.

Adaptation, Physiological↗
PubMed2004

Mediators of non-adrenergic non-cholinergic inhibitory neurotransmission in porcine jejunum.

The purpose of this study was to determine the non-adrenergic non-cholinergic inhibitory neurotransmitter in pig jejunum. Intracellular electrical activity was recorded from circular smooth muscle cells. Inhibitory junction potentials (IJPs) evoked by electrical field stimulation were inhibited by tetrodotoxin (1 micromol L(-1)), omega-conotoxin GVIA (0.1 micromol L(-1)) tetrodotoxin, apamin (1 micromol L(-1)), 1-[6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U-73122; 10 micromol L(-1)) but not by N omega-nitro-l-arginine (l-NNA; 100 micromol L(-1)), haemoglobin (10 micromol L(-1)), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 micromol L(-1)) or 9-(tetrahydro-2-furyl)adenine (SQ-22536; 10 micromol L(-1)). S-nitroso-N-acetylpenicillamine (SNAP) hyperpolarized the membrane potential. This was inhibited by ODQ (3 micromol L(-1)) and charybdotoxin (0.1 micromol L(-1)). Adenosine-5-triphosphate (ATP; 100 micromol L(-1)) and 2-methylthio ATP (2-MeS-ATP; 100 micromol L(-1)) did not hyperpolarize the membrane potential and 6-N-N-diethyl-beta- gamma -dibromomethylene-d-adenosine-5'-triphosphate (ARL67156; 100 micromol L(-1)) did not modify IJPs. Carbon monoxide (CO; 10%) and tricarbonyl dichlororuthenium dimer ([Ru(CO3Cl2)]2; 100 micromol L(-1)) hyperpolarized the membrane potential however zinc, copper and tin protoporphyrin IX (100 micromol L(-1)) did not alter IJPs. Vasoactive intestinal peptide (VIP) hyperpolarized the membrane potential but 4-Cl-d-Phe6-Leu17-VIP (1 micromol L(-1)) did not modify IJPs. Pituitary adenylate cyclase activating peptide (PACAP)38 (0.5 micromol L(-1)) hyperpolarized the membrane potential. This was inhibited by apamin (1 micromol L(-1)) but not by tetrodotoxin (1 micromol L(-1)). Pituitary adenylate cyclase activating peptide6-38 (1 micromol L(-1)) inhibited IJPs. These data suggest that inhibitory neurotransmission in pig jejunum is mediated partly by PACAP.

Adenosine Triphosphate↗
PubMed2004

Histoplasmosis in Australia: a report of a case with a review of the literature.

Histoplasmosis is a rare but serious fungal infection commonly presenting as mucosal ulceration of the oral cavity. It is increasingly recognized in Australia but the source of infection remains obscure and it is likely to be under-diagnosed. We report a case of chronic mucosal ulceration which failed to fully respond to periodontal therapy. Histology and culture of a gingival biopsy was consistent with histoplasmosis, and the patient responded favourably to treatment with oral itraconazole. Histoplasmosis may present to general dental practitioners as chronic mucosal ulceration and should be considered in the differential diagnosis of such lesions. Diagnosis is best made by culture and histology of biopsy specimens.

Antifungal Agents↗
PubMed2003

Personal digital assistant infectious diseases applications for health care professionals.

Personal digital assistants (PDAs; also known as "handheld computers," "pocket personal computers," and Palm Pilots) provide immediate access to vital and clinically relevant infectious diseases information at the point of care. Several infectious diseases applications are available that provide information on pathogens, diagnosis, medication, and treatment. In this article, 4 infectious diseases PDA applications are reviewed: ePocrates ID (part of ePocrates Rx Pro), the Johns Hopkins Division of Infectious Diseases Antibiotic Guide, the 2002 Sanford Guide to Antimicrobial Therapy, and Infectious Diseases and Antimicrobials Notes. Drug information, including clinical pharmacology, dosing in patients with renal insufficiency, adverse reactions, and drug interactions, is evaluated for completeness and accuracy by comparison of each application with the package insert. Treatment recommendations for 6 diseases are compared with current practice guidelines. Each PDA infectious diseases application reviewed has unique advantages and disadvantages. This critical review will help health care professionals select the infectious diseases PDA application best tailored to meet their individual information needs.

Anti-Bacterial Agents↗
PubMed2003

Slow binocular rivalry in bipolar disorder.

BACKGROUND: The rate of binocular rivalry has been reported to be slower in subjects with bipolar disorder than in controls when tested with drifting, vertical and horizontal gratings of high spatial frequency. METHOD: Here we assess the rate of binocular rivalry with stationary, vertical and horizontal gratings of low spatial frequency in 30 subjects with bipolar disorder, 30 age- and sex-matched controls, 18 subjects with schizophrenia and 18 subjects with major depression. Along with rivalry rate, the predominance of each of the rivaling images was assessed, as was the distribution of normalized rivalry intervals. RESULTS: The bipolar group demonstrated significantly slower rivalry than the control, schizophrenia and major depression groups. The schizophrenia and major depression groups did not differ significantly from the control group. Predominance values did not differ according to diagnosis and the distribution of normalized rivalry intervals was well described by a gamma function in all groups. CONCLUSIONS: The results provide further evidence that binocular rivalry is slow in bipolar disorder and demonstrate that rivalry predominance and the distribution of normalized rivalry intervals are not abnormal in bipolar disorder. It is also shown by comparison with previous work, that high strength stimuli more effectively distinguish bipolar from control subjects than low strength stimuli. The data on schizophrenia and major depression suggest the need for large-scale specificity trials. Further study is also required to assess genetic and pathophysiological factors as well as the potential effects of state, medication, and clinical and biological subtypes.

Adult↗
PubMed2003

Kit/stem cell factor receptor-induced phosphatidylinositol 3'-kinase signalling is not required for normal development and function of interstitial cells of Cajal in mouse gastrointestinal tract.

Signalling mediated by the receptor tyrosine kinase c-Kit is required for normal development of interstitial cells of Cajal (ICC). c-Kit activates several signalling pathways, including the phosphatidylinositol 3'-kinase (PI3'-kinase) pathway. The signals required for ICC development and maintenance are not well understood. Studies indicate a role for PI3'-kinase. We studied ICC function and morphology in mice homozygous for the tyrosine 719 to phenylalanine c-Kit mutation, which disrupts all PI3'-kinase binding to c-Kit. Functionally, the electrical slow waves in the jejunum and inhibitory junction potentials were normal in adult mutants. Morphologically, the distribution of ICC was not altered in mutants. There was no difference in the density of ICC in the jejunum of adults or newborns from quantitative analysis of c-Kit immunoreactivity. The number of ICC obtained in culture was the same using mutants or wild-type littermates. The density and organization of nerves in the jejunum of mutants was not affected. Deletion of c-Kit-induced PI3'-kinase signalling does not affect the function or development of ICC in the mouse. This is an important and counterintuitive result, given the role of PI3'-kinase signalling downstream of c-Kit and the role of both c-Kit and PI3'-kinase individually in ICC development.

Animals↗
PubMed2003

Morphological characteristics and immunohistochemical detection of nicotinic acetylcholine receptors on intestinofugal afferent neurones in guinea-pig colon.

Intestinofugal afferent neurones (IFANs) provide excitatory synaptic input to abdominal prevertebral ganglion neurones. Input is greatly reduced during blockade of nicotinic acetylcholine receptors (nAChRs) in the wall of the colon, suggesting two projection pathways: a direct pathway without synaptic interruption and an indirect pathway interrupted by at least one nicotinic cholinergic synapse. This study aimed to characterize the morphology of IFANs and examine the distribution of nAChRs on them. We identified IFANs in guinea-pig colon by retrograde labelling with fluorescent tracer DiI placed either on the lumbar colonic nerves in vitro or inferior mesenteric ganglion in vivo. Confocal laser scanning microscopy and computerized image-processing software were used for 3D image reconstruction. Approximately 70% of identified IFANs had Dogiel type I-like morphology, the remainder were Dogiel type II-like. In vivo labelled IFANs were injected with Lucifer Yellow and immunostained for nAChRs using monoclonal antibody MAb35. Approximately 3% of total plasma membrane surface of IFANs with Dogiel type I morphology had MAb35-IR. In contrast, <1% of membrane surface of IFANs with Dogiel type II morphology had MAb35-IR. The finding that IFANs displayed immunostaining for nAChRs suggests the presence of putative nicotinic synapses.

Animals↗
PubMed2002

Specialist health services for people with intellectual disability in Scotland.

BACKGROUND: People with intellectual disability (ID) are known to have a high prevalence of health needs, and to require access to specialist health services in addition to primary care and generic secondary care health services. However, there is no national database of each locality's specialist health service provision. Such a record would highlight variation in provision and enable benchmarking. METHOD: A 15-item questionnaire was developed which included questions on ID health services and staffing levels. This was sent to the chief executive of each of the 15 identified National Health Service primary care trusts/health boards which provide ID services in Scotland. The same questionnaire was also sent to the lead clinician/clinical director of each service. The results were converted to per 100 000 population per trust and presented in cumulative frequency tables to allow benchmarking. RESULTS: A response rate of 100% was achieved. The results show a wide range in the type of services provided by each locality in Scotland. Only three services (21%) have completed the process of resettlement. There was a wide-ranging variability in the number of beds/day places and professionals employed per 100 000 population per trust. CONCLUSIONS: There is widespread diversity in the service provision between different parts of Scotland. Geographical distances and responsibilities for service provision to remote and rural communities did not appear to account for these differences.

Adolescent↗
PubMed2002

Relationship between colonic motility and cholinergic mechanosensory afferent synaptic input to mouse superior mesenteric ganglion.

Abstract Abdominal prevertebral ganglion neurones receive excitatory synaptic input from intestinofugal neurones. To better understand the physiological significance of this input, we examined the relationship between synaptic input to mouse superior mesenteric ganglion (SMG) neurones and intracolonic pressure and volume changes that accompany spontaneous colonic contractions in vitro. Electrical activity was recorded intracellularly from SMG neurones in ganglia attached to a segment of distal colon. The majority of neurones examined received ongoing fast excitatory potentials (F-EPSPs). F-EPSP frequency increased when the colon was distended with fluid and during spontaneous increases in colonic volume that accompanied colonic relaxation. In contrast, F-EPSP frequency in SMG neurones decreased when the colon emptied, and remained at a reduced frequency until the colon refilled and volume increased. Nicotinic blockade of the colon abolished spontaneous colonic contractions and reduced or abolished synaptic input to SMG neurones, suggesting that most of the synaptic input arose from second or higher order neurones. Retrograde labelling identified cell bodies of intestinofugal neurones in myenteric ganglia. Most had short, club-like dendritic processes and appeared uni-axonal. These results show that mechanosensory intestinofugal afferent nerves monitor intracolonic volume changes.

Animals↗
PubMed2002

SCN5A is expressed in human jejunal circular smooth muscle cells.

Tetrodotoxin-resistant Na+currents are expressed in a variety of muscle cells including human jejunal circular smooth muscle (HJCSM) cells. The aim of this study was to determine the molecular identity of the pore-forming alpha-subunit of the HJCSM Na+ channel. Degenerate primers identified a cDNA fragment of 1.5 kb with 99% nucleotide homology with human cardiac SCN5A. The identified clone was also amplified from single smooth muscle cells by reverse transcriptase-polymerase chain reaction (RT-PCR). Northern blot analysis showed expression of full-length SCN5A. Laser capture microdissection was used to obtain highly purified populations of HJCSM cells. RT-PCR on the harvested cells showed that SCN5A was present in circular but not in longitudinal muscle. A similar result was obtained using a pan-Na+ channel antibody. The full-length sequence for SCN5A was obtained by combining standard polymerase chain reaction with 5' and 3' rapid amplification of cDNA end techniques. The intestinal SCN5A was nearly identical to the cardiac SCN5A. The data indicate that SCN5A is more widely distributed than previously thought and encodes the pore-forming alpha-subunit of the tetrodotoxin-resistant Na+ current in HJCSM cells.

Gene Expression Regulation↗
PubMed2002

Prevertebral ganglia and intestinofugal afferent neurones.

Intestinofugal afferent neurones (IFANs) are a unique subset of myenteric ganglion neurones that regulate normal gastrointestinal function. The IFANs relaying mechanosensory information to sympathetic neurones of the prevertebral ganglion (PVG) function as volume detectors. It is possible that mechanosensory information arriving in the PVG via axon collaterals of visceral spinal afferent nerves can be modulated entirely within the PVG itself.

Ganglia, Autonomic↗
PubMed2002

DNA damage and micronucleus induction in human leukocytes after acute in vitro exposure to a 1.9 GHz continuous-wave radiofrequency field.

Human blood cultures were exposed to a 1.9 GHz continuous-wave (CW) radiofrequency (RF) field for 2 h using a series of six circularly polarized, cylindrical waveguides. Mean specific absorption rates (SARs) of 0.0, 0.1, 0.26, 0.92, 2.4 and 10 W/kg were achieved, and the temperature within the cultures during a 2-h exposure was maintained at 37.0 +/- 0.5 degrees C. Concurrent negative (incubator) and positive (1.5 Gy (137)Cs gamma radiation) control cultures were run for each experiment. DNA damage was quantified immediately after RF-field exposure using the alkaline comet assay, and four parameters (tail ratio, tail moment, comet length and tail length) were used to assess DNA damage for each comet. No evidence of increased primary DNA damage was detected by any parameter for RF-field-exposed cultures at any SAR tested. The formation of micronuclei in the RF-field-exposed blood cell cultures was assessed using the cytokinesis-block micronucleus assay. There was no significant difference in the binucleated cell frequency, incidence of micronucleated binucleated cells, or total incidence of micronuclei between any of the RF-field-exposed cultures and the sham-exposed controls at any SAR tested. These results do not support the hypothesis that acute, nonthermalizing 1.9 GHz CW RF-field exposure causes DNA damage in cultured human leukocytes.

Adult↗
PubMed2001

Evaluation of parameters critical to observing proteins inside living Escherichia coli by in-cell NMR spectroscopy.

Our recently developed in-cell NMR procedure now enables one to observe protein conformations inside living cells. Optimization of the technique demonstrates that distinguishing the signals produced by a single protein species depends critically on protein overexpression levels and the correlation time in the cytoplasm. Less relevant is the selective incorporation of (15)N. Poorly expressed proteins, insoluble proteins, and proteins that cannot tumble freely due to associations within the cell cannot yet be observed. We show in-cell NMR spectra of bacterial NmerA and human calmodulin and discuss limitations of the technique as well as prospects for future applications.

Amino Acids↗