Magnetoencephalographic evidence for non-geniculostriate visual input to human cortical area V5

The aim of this study was to establish whether there is non-geniculostriate input to the extrastriate motion-sensitive area V5 in humans. Responses were measured with a SQUID neuro-magnetometer to motion stimuli presented within the blind hemifield of GY, a well-documented subject with a complete absence of the left primary visual cortical area V1. The motion stimulus was a 0.5c/deg, rapidly drifting (16Hz) achromatic sinusoidal grating. With this stimulus, the magnetic responses recorded over the temporo-parieto-occipital region in normals are well modelled by localized current sources in areas V1 and V5 (Anderson, S. J. et al., Proceedings of the Royal Society, London, Series B, 1996, 263, 423-431). As a control, evoked responses were measured to a 1.0 c/deg, stationary, photometrically isoluminant red/green sinusoidal grating. With the chromatic stimulus, the principal component of the magnetic responses recorded over the occipital pole in normals is well modelled by a current source in area V1 (Fylan, F. et al., Investigative Ophthalmology and Visual Science, 1995, 36, s1053). Both stimuli subtended 4 deg vertically by 6 deg horizontally, positioned such that the stimulus extended beyond the area of macular sparing into the lower field quadrant of the blind (or sighted) hemifield. Chromatic stimuli failed to evoked responses from GY's blind (contralateral) hemifield, consistent with there being no V1 activity in his left cortical hemisphere. However, motion stimuli did evoke responses from GY's blind hemifield, originating from a location consistent with activity in area V5. We further observed that both colour and motion stimuli evoked responses from GY's sighted (ipsilateral) hemifield. We conclude that there is non-geniculostriate input to extrastriate motion-sensitive areas in the human visual system, and that this pathway subserves the residual visual sensitivity to motion in the blind hemifield that has been demonstrated psychophysically in observer GY.     

Substantial narrowing of the Niemann-Pick C candidate interval by yeast artificial chromosome complementation

Niemann-Pick disease type C (NP-C) is an autosomal recessive lipidosis linked to chromosome 18q11-12, characterized by lysosomal accumulation of unesterified cholesterol and delayed induction of cholesterol-mediated homeostatic responses. This cellular phenotype is identifiable cytologically by filipin staining and biochemically by measurement of low-density lipoprotein-derived cholesterol esterification. The mutant Chinese hamster ovary cell line (CT60), which displays the NP-C cellular phenotype, was used as the recipient for a complementation assay after somatic cell fusions with normal and NP-C murine cells suggested that this Chinese hamster ovary cell line carries an alteration(s) in the hamster homolog(s) of NP-C. To narrow rapidly the candidate interval for NP-C, three overlapping yeast artificial chromosomes (YACs) spanning the 1 centimorgan human NP-C interval were introduced stably into CT60 cells and analyzed for correction of the cellular phenotype. Only YAC 911D5 complemented the NP-C phenotype, as evidenced by cytological and biochemical analyses, whereas no complementation was obtained from the other two YACs within the interval or from a YAC derived from chromosome 7. Fluorescent in situ hybridization indicated that YAC 911D5 was integrated at a single site per CT60 genome. These data substantially narrow the NP-C critical interval and should greatly simplify the identification of the gene responsible in mouse and man. This is the first demonstration of YAC complementation as a valuable adjunct strategy for positional cloning of a human gene.     

Measurement of adenylylcyclase activity in the AV nodal region of the canine heart: evidence for inhibition by adenosine and acetylcholine

We simultaneously recorded gastric emptying of radio-opaque markers (ROMs) and monitored serial changes in plasma acetaminophen (AAP) levels to demonstrate the relationship between the ROM and the AAP methods, and we investigated the effect of a single intravenous dose of erythromycin (EM) on gastric emptying in healthy human subjects. After an overnight fast, subjects were randomized to receive either placebo or EM lactobionate (Abbott, North Chicago, IL, USA) 250 mg intravenously in a single dose, given immediately before a standard meal. Subjects ingested 1.5 g of AAP and ROMs with the test meal. A supine plain abdominal radiograph was taken 1, 2, 3, and 6 h after ingestion of the test meal. Peripheral blood samples were obtained 0, 0.5, 1, 1.5, 2, 3, and 6 h after ingestion of the test meal. EM significantly accelerated gastric emptying of ROMs. By 6 h, no markers remained in the stomach in any of the subjects in the placebo or EM groups. By 120 min, half of the ROMs had passed into the duodenum in 12.5% of subjects after placebo, whereas EM injection resulted in gastric emptying of half of the ROMs in all subjects. There was no difference in plasma AAP concentration between the placebo and EM groups. There were significant correlations between maximum plasma AAP concentration and gastric emptying of ROMs 120 min after ingestion (r = 0.546; P = 0.019), and between time of maximum plasma AAP concentration and gastric emptying of ROMs 120 min after ingestion (r = -0.568; P = 0.014). The time taken to reach the peak concentrations ranged from 30 to 90 min after ingestion, whereas most ROMs were emptied 120 min after ingestion. We conclude that the gastric emptying assessed by ROMs and by serial changes in plasma AAP level are good, non-invasive, clinically applicable tests, with a significant correlation between the two tests. A single intravenous dose of EM had a prokinetic effect on gastric emptying, assessed by ROMs, in healthy human subjects.     

Microlesions of the ventromedial nucleus of the hypothalamus: Effects on sociosexual behaviors in male rats.

Electrolytic microlesions aimed at the dorsomedial portion of the ventromedial nucleus (VMN) of the hypothalamus were generated, and effects on copulation, 50-kHz vocalizations, scent marking, and sexual motivation were measured. Male rats were tested before and after lesions, after castration, and after testosterone replacement. Three control groups were used: One received sham surgery, another received no surgery or testosterone replacement, and a 3rd received lesions primarily outside the VMN. VMN lesions produced impairments in testosterone's ability to restore ultrasonic vocalizations and scent marking, assessed with 2 different test methods. Copulation, sexual motivation, and weight gain were largely unaffected, although some differences were observed in copulatory efficiency. The authors conclude that the integrity of the VMN is important for full expression of sociosexual behaviors in male rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thermosiphon circulation in solar water heaters incorporating evacuated tubular collectors and a novel water-in-glass manifold

A study is reported of thermosiphon circulation in solar water heaters incorporating glass tubular evacuated collectors and a water-in-glass manifold of extremely simple design. The manifold is characterised by the absence of partitioning of the inner volumes of the absorber tubes into inlet/outlet channels and buoyancy effects are utilised to convey heat to a header pipe at the open end of the tubes. Solar energy input to the tubes has been simulated by electric heating. The thermosiphon system design is unusual in that there are no risers within the collector tubes, thus, the pressure head responsible for thermosiphon flow originates entirely from relatively short pipe runs between manifold and storage tank. Thermosiphon flow has been measured for a number of system designs and a wide range of operating conditions. The relative impedances of the system components has been evaluated allowing optimization of the system design. An investigation of the effect of withdrawal of hot water from the storage tank, with associated injection of cold water to the bottom of the tank, has illustrated that the self-regulating nature of the thermosiphoning system results in a large proportion of heat stored in the wate filled collector tubes being effieciently transferred to the storage tank, providing some water is drawn off intermittently.     

Validation of [13C]urea breath test for Helicobacter pylori using a simple gas chromatograph-mass selective detector

OBJECTIVE: Isotope ratio mass spectrometry (IRMS) is the accepted method for accurately measuring the 13CO2:12CO2 ratio in the non-invasive and non-radioactive [13C]urea breath test (13C-UBT) for Helicobactor pylori. The IRMS instrument, an expensive and highly specialized analyser, is rarely available. The objective of this project was to modify and validate the use of a simple bench-top gas chromatograph-mass selective detector (GC-MSD) for 13C-UBT. METHODS: Breath samples from 71 patients were taken at baseline and 30 min after ingestion of 100 mg [13C]urea. The breath samples were analysed using GC-MSD in the selected ion monitoring mode. The reference 13CO2:12CO2 ratio was from NBS19 obtained from the US National Institute of Standards and Technology. 13CO2:12CO2 ratios of the breath samples were determined. Excess delta per thousand (per mil, delta/thousand) of the 30 min sample over the baseline (deltadelta/thousand) of > or = 6deltadelta/thousand was considered H. pylori positive. Results from 13C-UBT and histology determined blind to each other were compared. RESULTS: The coefficient of variation of the reference 13CO2:12CO2 ratio was 0.06%. Using histology as the 'gold standard', the sensitivity (97.9%) and specificity (95.8%) of the GC-MSD 13C-UBT were comparable to those of other methods of H. pylori diagnosis. CONCLUSION: A gas chromatograph coupled to a mass selective detector that is available in many analytical and biomedical laboratories can be used for the 13C-UBT. This method will increase the availability and reduce the cost of this non-invasive, non-radioactive diagnostic test.     

Organization of the genetic locus for chicken myosin light chain kinase is complex: multiple proteins are encoded and exhibit differential expression and localization

We report that the genetic locus that encodes vertebrate smooth muscle and nonmuscle myosin light chain kinase (MLCK) and kinase-related protein (KRP) has a complex arrangement and a complex pattern of expression. Three proteins are encoded by 31 exons that have only one variation, that of the first exon of KRP, and the genomic locus spans approximately 100 kb of DNA. The three proteins can differ in their relative abundance and localization among tissues and with development. MLCK is a calmodulin (CaM) regulated protein kinase that phosphorylates the light chain of myosin II. The chicken has two MLCK isoforms encoded by the MLCK/KRP locus. KRP does not bind CaM and is not a protein kinase. However, KRP binds to and regulates the structure of myosin II. Thus, KRP and MLCK have the same subcellular target, the myosin II molecular motor system. We examined the tissue and cellular localization of KRP and MLCK in the chicken embryo and in adult chicken tissues. We report on the selective localization of KRP and MLCK among and within tissues and on a differential distribution of the proteins between embryonic and adult tissues. The results fill a void in our knowledge about the organization of the MLCK/KRP genetic locus, which appears to be a late evolving regulatory paradigm, and suggest an independent and complex regulation of expression of the gene products from the MLCK/KRP genetic locus that may reflect a basic principle found in other eukaryotic gene clusters that encode functionally linked proteins.