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PubMed1984

The time course of miniature endplate currents and its modification by receptor blockade and ethanol.

Miniature endplate currents (MEPCs) recorded from mouse diaphragms with a point voltage clamp, without inhibition of acetylcholinesterase (AChE) and in the absence of any drug, showed in their decay phase consistent deviations from an exponential time course, consisting of (a) "curvature," a progressive increase of decay rate during most of the decay phase, followed by (b) "late" tails. Both phenomena persisted when MEPCs (and channel lifetime) were prolonged by ethanol. Curvature was increased by muscle fiber depolarization and decreased by hyperpolarization. Receptor blockade by (+)-tubocurarine, alpha-bungarotoxin, hexamethonium, or myasthenic IgG accelerated the decay of the main part of MEPCs and eliminated curvature; the time constant of MEPCs became close to the channel time constant. We conclude that curvature arises from repeated action of ACh with cooperativity in ACh-receptor interaction; the voltage sensitivity of curvature follows from the voltage sensitivity of channel closing. Ethanol, in addition to its effect to prolong channel lifetime, enhances the tendency of ACh to act more than once to open channels before being lost to the system. Analysis of the rising phase of the MEPC, in terms of driving functions, also indicated that ethanol promotes channel opening by ACh; this action can account for a substantial increase of MEPC height by ethanol when MEPCs are made small by receptor blockade. Driving functions were also voltage sensitive, in a manner indicating acceleration of channel opening, but reduction of channel conductance, with hyperpolarization. Poisoning or inhibition of AChE prolonged MEPCs without altering the duration of ionic channels. Since ethanol caused further prolongation of MEPCs after poisoning of AChE, with little change in MEPC height, we conclude that the extension of mean channel lifetime by ethanol is accompanied by a similar extension of ACh binding to receptors. After poisoning of AChE, MEPCs became very variable in time course and the decay rate (tau-1) was correlated with MEPC height with a slope of log tau vs. log height of 0.77 for MEPCs of greater than 60% mean size. This slope is larger than expected from cooperativity in ACh-receptor interaction. Correlation of tau and height of MEPCs also exists when AChE is intact; the slope of log tau vs. log height was 0.12 with or without prolongation of MEPCs by ethanol.

Acetylcholine↗

PubMed1989

Protons resolve dual effects of calcium on miniature end-plate potential frequency at frog neuromuscular junctions.

Inhibition of transmitter release by protons (H+) was studied at the frog neuromuscular junction at various extracellular concentrations of calcium ([Ca++]o) and potassium ([K+]o) by recording miniature end-plate potential (MEPP) frequency with the intracellular microelectrode. H+ decreased K+ -stimulated MEPP frequency. A double logarithmic graph of MEPP frequency at 7.5 mM K+ vs. [H+]o yielded a straight line with negative slope. At 10 mM K+, there was a parallel shift to the right of the graph. According to the surface charge model, K+ acts solely to depolarize the prejunctional membrane in accordance with the Nernst equation. By decreasing the prejunctional negative surface charge, H+ decreases K+ -stimulated MEPP frequency by decreasing [Ca++]o at the Ca++ channel. An estimated pKa of 4.20 may represent an acidic site at the Ca++ channel associated with Ca++ influx. As [Ca++]o increased above 1 mM for pH 7.40 and 10 mM K+, MEPP frequency decreased, i.e., the inhibitory component of dual effects of Ca++ occurred. At pH 6.40, the inhibitory component was abolished, unmasking the stimulatory effect of Ca++ on MEPP frequency. Reversal of Ca++ action by H+ could not be explained by surface charge theory alone. A double logarithmic graph of MEPP frequency vs. [K+]o at 8.5-10.5 mM was linear with a slope of 4. There were parallel shifts to the right of this graph for changes in pH from 7.40 to 6.90 and in [Ca++]o from 1 to 2.5 mM. These results are explained on the hypothesis that K+ also acts at an acidic prejunctional site to increase Ca++ -dependent quantal transmitter release. This action of K+ was inhibited by H+ and raised Ca++. Based on kinetic theory, the estimated pKa of the acidic prejunctional K+ site was 6.31. Based on free energy calculations, its cation preference was H+ greater than K+ greater than Ca++.

Animals↗

PubMed1996

Microdosimetric analysis of radiation from a clinical mammography machine using realistic breast phantoms and a miniature proportional counter.

We have measured the microdosimetric spectra of a Senographe 600T mammography machine employing an Mo target with 0.8 mm Be inherent filtration and 0.03 mm Mo added filtration, giving a half-value layer of 0.35 mm A1 at 28 kVp. In all of our measurements a large collimator producing a 24 cm x 30 cm field at 65 cm was used. Two different phantom compositions differing in the ratio of adipose to fibroglandular tissue were compared, using simulated breast material from Nuclear Associates. Spectra were taken at various depths and locations in simulated breasts of 3.4 and 5 cm thickness. The detector used was a miniature proportional counter having outer dimensions of 5 cm x 1.8 cm diameter, with a sensitive volume 0.5 mm x 0.5 mm. The small dimensions of the counter and the cavity allowed total embedding in the breast material with minimal disturbance of the photon and secondary electron spectrum. Our results show that there can be changes in the radiation quality amounting to as much as 17% (as measured by the dose mean lineal energy. yD) between breasts of different thickness, at the same relative position within the breast. There is little difference due to breast composition.

Breast↗

PubMed2002

Characterization of miniature tissue-equivalent proportional counters for neutron radiotherapy applications.

A miniature tissue-equivalent proportional counter (TEPC) system has been developed to facilitate microdosimetric measurements in high-flux mixed fields. Counters with collecting volumes of 12.3 and 2.65 mm3 have been constructed using various tissue-equivalent wall materials, including those loaded with 10B for evaluation of the effects of the boron neutron capture reaction. These counters provide a measure of both the absorbed dose and associated radiation quality, allowing an assessment of the utility and relative effectiveness of various neutron radiotherapy techniques such as boron neutron capture therapy (BNCT), boron neutron capture enhanced fast neutron therapy (BNCEFNT) and intensity modulated neutron radiotherapy (IMNRT). An evaluation of the physical parameters affecting the measured microdosimetric spectrum, the gas multiplication characteristics and the measurement of absorbed dose is presented. In addition, important aspects of the calibration and low energy extrapolation techniques for the microdosimetric spectrum are provided.

Boron Neutron Capture Therapy↗

PubMed2004

Miniature ultrasonic probe construction for minimal access surgery.

The increasing use of minimal access techniques for surgery has produced a need for imaging technologies that can be used during such interventions. Ultrasound imaging has the advantage that the probe itself can be interventional. Interventional ultrasound probes must be sufficiently small to gain access to the surgical site, and any rigid portion must be limited in length to permit adequate flexibility. In practice this means the ultrasound probes have to operate at high frequencies, and a set of design curves have been produced which relate the number of elements and the ultrasound frequency to the probe dimensions for both linear and cylindrical array configurations. Constructing high-frequency sub-miniature probes presents a number of technical challenges, in particular relating to interconnects and packaging. Solutions to these challenges are discussed using the fabrication of a 1 mm diameter intravascular probe as an example.

Equipment Design↗

PubMed1987

Ultraviolet radiometry of clinical sources with a miniature multijunction thermopile.

Three versions of the Dexter 2M miniature multijunction thermopile were evaluated for the radiometry of clinical ultraviolet radiation (UVR) sources. The acceptance angle had been increased in two of these devices, and one also contained an additional ceramic heat sink under its receiver element. Measurements were made of their absolute sensitivity and linearity, and their response to various UVR sources was compared to that of Hilger Schwarz FT17 and FT32 vacuum compensated thermopiles. Both of the acceptance angle modifications yielded an angular response less than that of the wide-angle FT32 thermopile. The additional ceramic heat sink diminished, but did not eliminate, the initial surge in the 2M thermopile output voltage following exposure. Under constant irradiance, the 2M output voltage was stable after the initial surge had decayed, even without the additional heat sink. It was concluded that irradiance measurements should be made after the output voltage had stabilised. Any version of the 2M thermopile could be used for relative day-to-day monitoring of all UVR sources, and the version with the widest acceptance angle could be used for the absolute radiometry of certain extended sources.

Evaluation Studies as Topic↗

PubMed2002

A prototype microfluidic platform for miniaturization and automation of serial dilution and dose-response assays.

A novel microfluidic device was designed and developed to miniaturize, multiplex, and automate serial dilution and three-reagent dose-response assays using submicroliter quantities of reagents. This prototype microfluidic device can be used to measure enzyme kinetics and to test a chemical lead's response to a target by fluorescent readout using common plate readers and detection systems. The prototype microfluidic system yielded serial dilution and dose-response assay data comparable to results obtained from manual titrations and reagent additions performed using a microwell plate. Enzyme kinetics were highly reproducible using these devices, although Michaelis-Menten kinetics results differed from those obtained in the microwell plate. In all cases reported here, assays performed on the microfluidic format required lower volumes of reagents compared with the microwell plate. In addition to savings in reagent consumption, the microfluidic devices and bench-top instruments offer additional advantages over conventional solutions, including a small footprint and compatibility with commercially available fluorescence detectors. Future directions for the prototype technology are discussed.

Automation↗

PubMed1981

Prostaglandins and their metabolites in the gastrointestinal tract of Yucatan miniature swine.

Concentration of prostaglandins E1, E2, F2alpha, and 15 keto, 13, 14-dihydro F2alpha (MPF2alpha), were measured in gastric, duodenal, jejunal, and ileal mucosa, and in the luminal contents of these gastrointestinal segments in miniature swine at 30, 60, and 120 min after they ingested a liquid nutrient meal. Large quantities of E1 and F2alpha were present in gastric contents at 30 min with lesser amounts of E2 and MPF2alpha. The concentrations of E1, E2, and F2alpha in the gastric contents decreased progressively with time after feeding. The total quantity and the concentrations of E1 and F2alpha decreased with passage of ingesta through the duodenum and jejunum. Mucosal concentrations of E1 and F2alpha were greatest in the duodenum and proximal jejunum and lowest in gastric mucosa. These results indicate that there is considerable production and metabolism of prostaglandins in the gastrointestinal tract, with major amounts secreted into the luminal contents of the stomach and duodenum after food intake.

Alprostadil↗

PubMed1981

Effects of osmolality of liquid nutrient diets on meal passage and nutrient absorption in Yucatan miniature swine.

The effects of varying the osmolality of liquid nutrient diets on the absorption of water, electrolytes, and carbohydrate from the small intestine were studied in Yucatan miniature swine. Pigs were killed and their gastrointestinal contents recovered at either 30 or 60 min after consuming liquid diets adjusted to 340, 450, 540, or 700 mOsm/kg and labeled with 3H2O, 22NaCl, U--14C-sucrose, and 51Cr-EDTA as a passage marker. Intragastric dilution and gastric emptying were not effected by diet osmolality. Gastric contents of all pigs converged toward 450 mOsm/kg, and osmolality of small intestine contents did not differ between diets. The absorption of carbohydrate, water, sodium, and potassium from jejunal contents increased with increasing osmolality of the diets. The rates of appearance of 3H, 22Na, and 14C in plasma also increased with increasing diet osmolality. These findings suggest that moderately hyperosmotic liquid diets may be beneficial, as compared with isoosmotic diets.

Absorption↗

PubMed1994

Patient-controlled analgesia using a miniature electrochemically driven infusion pump.

We describe a miniature electrochemically driven, wrist-worn infusion pump. Generation of gas by an electrolytic reaction compresses a reservoir containing medication and provides a predictable and controllable infusion rate. The pump was used for patient-controlled analgesia (PCA) in women who required analgesia after Caesarean section. It was accepted readily and was convenient for both patients and nursing staff. This portable system, using a novel motive force, has advantages of convenience over larger systems and has sophisticated features not present in existing small systems. It has potential as a routine PCA device and it may have uses in other situations requiring convenient infusion or intermittent injection in an ambulatory setting.

Analgesia, Obstetrical↗

PubMed1999

Sevoflurane anaesthesia with an Oxford Miniature Vaporizer in vaporizer inside circle mode.

Anaesthesia was induced and maintained successfully with sevoflurane using an Oxford Miniature Vaporizer (OMV) in vaporizer inside circle (VIC) mode. With continuous monitoring using the Drager Narkomed 4 machine agent analyser, the expired sevoflurane concentration was monitored and controlled easily. During induction, there was no cardiovascular depression, apnoea or coughing, but involuntary movements and breath-holding were common.

Adult↗

PubMed2006

Miniature synaptic currents become neurotoxic to chronically silenced neurons.

When deprived of spontaneous ongoing network activity by chronic exposure to tetrodotoxin (TTX), cultured cortical neurons retract their dendrites, lose dendritic spines, and degenerate over a period of 1-2 weeks. Electrophysiological properties of these slowly degenerating neurons prior to their death are normal, but they express very large miniature excitatory postsynaptic currents (mEPSCs). Chronic blockade of these mEPSCs by the alpha-amino-5-hydroxy-3-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist 6,7-Dinitroquinoxaline-2,3-dione (DNQX) had no effect of its own on cell survival, yet, paradoxically, it protected the TTX-silenced neurons from degenerating. TTX-treated neurons also exhibited deficient Ca(2+) clearance mechanisms. Thus, upscaled mEPSCs are sufficient to trigger apoptotic processes in otherwise chronically silenced neurons.

Action Potentials↗

PubMed2001

Potentiality of optical diffraction grating technology in the fabrication of miniaturized multicapillary chromatographic and electrophoresis columns.

A possible way of fabricating miniaturized multicapillary columns for gas and liquid chromatographs or electrophoresis devices containing many thousands of identical channels with a width (or depth) of approximately 1-30 microm by means of industrial technology for the production of optical plane reflecting diffraction gratings is proposed.

Journal Article↗

PubMed1991

Mutational analysis of the Drosophila miniature-dusky (m-dy) locus: effects on cell size and circadian rhythms.

A mutational analysis has been performed to explore the function of the Drosophila melanogaster miniature-dusky (m-dy) locus. Mutations at this locus affect wing development, fertility and behavior. The genetic characterization of 13 different mutations suggests that m and dy variants are alleles of a single complex gene. All of these mutations alter wing size, apparently by reducing the volume of individual epidermal cells of the developing wing. In m mutants, epidermal cell boundaries persist in the mature wing, whereas they normally degenerate 1-2 hr after eclosion in wild-type or dy flies. This has permitted the direct visualization of cell size differences among several m mutants. Mutations at the m-dy locus also affect behavioral processes. Three out of nine dy alleles (dyn1, dyn3 and dyn4) lengthen the circadian period of the activity and eclosion rhythms by approximately 1.5 hr. In contrast, m mutants have normal circadian periods, but an abnormally large percentage of individuals express aperiodic bouts of activity. These behavior genetic studies also indicate that an existing "rhythm" mutation known as Andante is an allele of the m-dy locus. The differential effects of certain m-dy mutations on wing and behavioral phenotypes suggest that separable domains of function exist within this locus.

Alleles↗

PubMed2003

Genome-wide analysis of mariner-like transposable elements in rice reveals complex relationships with stowaway miniature inverted repeat transposable elements (MITEs).

Stowaway is a superfamily of miniature inverted repeat transposable elements (MITEs) that is widespread and abundant in plant genomes. Like other MITEs, however, its origin and mode of amplification are poorly understood. Several lines of evidence point to plant mariner-like elements (MLEs) as the autonomous partners of the nonautonomous Stowaway MITEs. To better understand this relationship, we have taken advantage of the nearly complete genome sequences of two rice subspecies to generate the first inventory of virtually all MLEs and Stowaway families coexisting in a single plant species. Thirty-four different MLEs were found to group into three major clades and 25 families. More than 22,000 Stowaway MITEs were identified and classified into 36 families. On the basis of detailed sequence comparisons, MLEs were confirmed to be the best candidate autonomous elements for Stowaway MITEs. Surprisingly, however, sequence similarity between MLE and Stowaway families was restricted to the terminal inverted repeats (TIRs) and, in a few cases, to adjacent subterminal sequences. These data suggest a model whereby most of the Stowaway MITEs in rice were cross-mobilized by MLE transposases encoded by distantly related elements.

Base Sequence↗

PubMed2004

PIF- and Pong-like transposable elements: distribution, evolution and relationship with Tourist-like miniature inverted-repeat transposable elements.

Miniature inverted-repeat transposable elements (MITEs) are short, nonautonomous DNA elements that are widespread and abundant in plant genomes. Most of the hundreds of thousands of MITEs identified to date have been divided into two major groups on the basis of shared structural and sequence characteristics: Tourist-like and Stowaway-like. Since MITEs have no coding capacity, they must rely on transposases encoded by other elements. Two active transposons, the maize P Instability Factor (PIF) and the rice Pong element, have recently been implicated as sources of transposase for Tourist-like MITEs. Here we report that PIF- and Pong-like elements are widespread, diverse, and abundant in eukaryotes with hundreds of element-associated transposases found in a variety of plant, animal, and fungal genomes. The availability of virtually the entire rice genome sequence facilitated the identification of all the PIF/Pong-like elements in this organism and permitted a comprehensive analysis of their relationship with Tourist-like MITEs. Taken together, our results indicate that PIF and Pong are founding members of a large eukaryotic transposon superfamily and that members of this superfamily are responsible for the origin and amplification of Tourist-like MITEs.

Amino Acid Sequence↗

PubMed1994

Attention and performance in miniature golf across the life span.

Highly skilled adolescent (15-19 years), young (25-35 years), middle-aged (50-57 years), and older (58-73 years) miniature golf players were examined in training and competitive conditions. Number of shots, heart rate, ratings of anxiety, and concentration time were registered. IN addition, two attentional subscales from the Test of Attentional and Interpersonal Style (TAIS) inventory (Nideffer, 1976) were administered. Results indicated (a) parallel increases of heart rate and rated anxiety in competition for all age groups, (b) improvement of motor performance in competition for adolescent and young-adult players, and deterioration of motor performance in competition for middle-aged and older players, and (c) increased concentration time for the two younger samples, and decreased concentration time for the two older samples in competition. As well, the TAIS data indicated greater self-perceived external and internal distractability in the two older, compared to the two younger samples. This age-related vulnerability to distractions was shown to partly mediate age differences in competitive motor performance. The overall pattern of outcome is discussed relative to the view that the adult aging process is associated with a deficit in the ability to handle situations of high arousal due to age-related deficits in a variety of basic cognitive capacities.

Adolescent↗

PubMedDate not supplied

Photoreceptor dysplasia (pd) in miniature schnauzer dogs: evaluation of candidate genes by molecular genetic analysis.

Photoreceptor dysplasia (pd) is one of a group of at least six distinct autosomal and one X-linked retinal disorders identified in dogs which are collectively known as progressive retinal atrophy (PRA). It is an early onset retinal disease identified in miniature schnauzer dogs, and pedigree analysis and breeding studies have established autosomal recessive inheritance of the disease. Using a gene-based approach, a number of retina-expressed genes, including some members of the phototransduction pathway, have been causally implicated in retinal diseases of humans and other animals. Here we examined seven such potential candidate genes (opsin, RDS/peripherin, ROM1, rod cGMP-gated cation channel alpha-subunit, and three subunits of transducin) for their causal association with the pd locus by testing segregation of intragenic markers with the disease locus, or, in the absence of informative polymorphisms, sequencing of the coding regions of the genes. Based on these results, we have conclusively excluded four photoreceptor-specific genes as candidates for pd by linkage analysis. For three other photoreceptor-specific genes, we did not find any mutation in the coding sequences of the genes and have excluded them provisionally. Formal exclusion would require investigation of the levels of expression of the candidate genes in pd-affected dogs relative to age-matched controls. At present we are building suitable informative pedigrees for the disease locus with a sufficient number of meiosis to be useful for genomewide screening. This should identify markers linked to the disease locus and eventually permit progress toward the identification of the photoreceptor dysplasia gene and the disease-causing mutation.

Animals↗