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Biomedical subjects

K Noble

Publications and source records attributed to K Noble.

11 recordsLinked to original sources
PubMed2004

Increased cholesterol decreases uterine activity: functional effects of cholesterol alteration in pregnant rat myometrium.

Uterine quiescence is essential for successful pregnancy. Cholesterol and triglycerides are markedly increased in pregnancy. Cholesterol is enriched in microdomains of the plasma membrane known as rafts and caveolae. Both lipid rafts and caveolae have been implicated in cellular signaling cascades. The purpose of this work was to investigate whether manipulation of cholesterol content alters uterine contractility. Late pregnancy (19-21 days) rats were humanely euthanized and strips of longitudinal myometrium were then dissected. Force and Ca(2+) measurements were simultaneously recorded and cholesterol increased by the addition of 5 mg/ml cholesterol or 0.25 mg/ml low-density lipoproteins (LDLs) or reduced by 2% methyl-beta-cyclodextrin (MCD) or 2 U/ml cholesterol oxidase addition to the perfusate. Both LDLs and cholesterol profoundly inhibited spontaneous uterine force production and associated Ca(2+) transients; frequency, amplitude, and duration of contraction were all significantly reduced compared with preceding control contractions. Force and Ca(2+) were also reduced by cholesterol when 1 nM oxytocin was used to stimulate the myometrium. Uterine activity was significantly increased by cholesterol extraction with MCD or cholesterol oxidase treatment. Electron microscopy confirmed the lipid raft disrupting effect of MCD, as formerly electron microscopy-visible caveolae in the myometrial cell membrane all but disappeared after MCD treatment. These data show that uterine smooth muscle cell cholesterol content is critically important for functional activity. A novel finding of our study is that cholesterol is inhibitory for force generation. It may be one of the mechanisms operating to maintain uterine quiescence throughout gestation and may also contribute to difficulties in labor suffered by obese women.

Animals↗
PubMed2004

Attention to single letters activates left extrastriate cortex.

Brain imaging studies examining the component processes of reading using words, non-words, and letter strings frequently report task-related activity in the left extrastriate cortex. Processing of these linguistic materials involves varying degrees of semantic, phonological, and orthographic analysis that are sensitive to individual differences in reading skill and history. In contrast, single letter processing becomes automatized early in life and is not modulated by later linguistic experience to the same degree as are words. In this study, skilled readers attended to different aspects (single letters, symbols, and colors) of an identical stimulus set during separate sessions of functional magnetic resonance imaging (fMRI). Whereas activation in some portions of ventral extrastriate cortex was shared by attention to both alphabetic and non-alphabetic features, a letter-specific area was identified in a portion of left extrastriate cortex (Brodmann's Area 37), lateral to the visual word form area. Our results demonstrate that while minimizing activity related to word-level lexical properties, cortical responses to letter recognition can be isolated from figural and color characteristics of simple stimuli. The practical utility of this finding is discussed in terms of early identification of reading disability.

Adolescent↗
PubMed2003

Calcium signaling and uterine contractility.

Changes in Ca(2+) signals within the myometrium have important functional consequences, as they determine contractility. We show that the basic phasic nature of uterine contractions, which is essential for successful labor, is critically dependent on Ca(2+) influx through voltage-gated L-type Ca(2+) channels, and hence in turn, on membrane potential. Thus changes in ion channel expression around term will play an important role in governing uterine excitability and contractility. There remains uncertainty about which channels are present in human myometrium and the nature of the pacemaker mechanism that initiates the action potential. The sarcoplasmic reticulum may augment, to a small extent, the necessary increase in [Ca(2+)] for contraction when agonists stimulate the uterus, but its main role appears to be to control excitability, acting as a negative feedback mechanism to limit contractions. Myosin light chain kinase activity and phosphorylation of myosin are essential components in the pathway of uterine contraction, once Ca(2+) has been elevated. Modulation of myosin light chain phosphatase activity can also influence contractions, but the effects are small compared with those modulating myosin light chain kinase. Ca(2+)-sensitizing pathways may not be utilized much in modulating normal phasic uterine activity, and caution is needed in extrapolating from in vitro experiments to in vivo conditions, especially because there may be redundant pathways. There is a need to study appropriate physiologic preparations, but these are not always available (eg, preterm laboring myometrium) and to combine functional studies with modern molecular approaches, to advance our understanding to a new level, from which better therapeutics will be developed.

Animals↗
PubMed2001

Comparison of permeating and nonpermeating cryoprotectants for mouse sperm cryopreservation.

Mouse sperm has proven to be more difficult to cryopreserve than sperm of other mammalian species. Published reports show that only three cryoprotectant agents (CPAs), alone or combined, have been studied: glycerol and dimethyl sulfoxide (DMSO), as permeating agents, and raffinose, as a nonpermeating agent. To date, the most consistent results for mouse sperm cryopreservation have been achieved by use of raffinose/skim milk as cryoprotectant with rapid cooling at 20 degrees C per minute. In this study, we compared the cryoprotection provided by permeating (glycerol, formamide, propanediol, DMSO, adonitol) or nonpermeating (lactose, raffinose, sucrose, trehalose, d-mannitol) compounds for freezing mouse sperm. Different solutions were made using 3% skim milk solution as the buffer or extender in which all different cryoprotectant agents were dissolved at a concentration of 0.3 M, with a final osmolality of approx. 400 mOsm. Sperm samples from CB6F1 (hybrid) and C57BL/6J (inbred) mice collected directly into each CPA were frozen/thawed under identical conditions. After thawing and CPA elimination (centrifugation) raffinose (59%), trehalose (61%), and sucrose (61%) sustained the best motility (P = < 0.1) of the nonpermeating agents, whereas the best of the permeating agents was DMSO (42%). Membrane integrity was analyzed and showed that the simple exposure (prefreeze) to sugars was less harmful than the exposure to glycols. Coincidentally, sperm frozen in trehalose (41%), raffinose (40.5%), and sucrose (37.5%) were the samples less injured among all different postthawed CPA tested. The in vitro fertilization results demonstrated that hybrid mouse spermatozoa frozen with sugars (lactose 80%, raffinose 80%, trehalose 79% of two-cell embryos production) were more fertile than those frozen with glycols (glycerol 11%).

Animals↗
PubMed2000

Oral reading in dementia.

Reading has been thought to consist of three main processing components: the orthographic, phonological, and semantic lexicons. In traditional psycholinguistic models, these components have been treated independently such that the selective dysfunction of one does not necessarily imply the breakdown of another. Recently, it has been proposed that a word's semantic representation is essential to oral reading such that a disturbance within the semantic lexicon will disrupt processing within the orthographic and/or phonological lexicons. From this view, semantic deterioration should lead to fragmentation of the other systems contributing to reading, resulting in a specific pattern of errors during oral reading. This would include (1) a larger than normal advantage for reading words with regular spelling-to-sound correspondence over words with exception spelling, as well as the production of "regularization errors" when reading exception words; and (2) a smaller than normal difference between reading real words and pronounceable nonwords, or pseudowords (PW's). We found that patients with Semantic Dementia generally conformed to these hypothesized patterns of reading difficulty. Despite the presence of a semantic impairment, however, patients with Alzheimer's Disease, Frontotemporal Dementia, and Progressive Non-Fluent Aphasia did not demonstrate these patterns of reading difficulty. Our findings suggest that not all semantic impairments invariably lead to the disruption of the orthographic and phonological lexicons.

Aged↗
PubMed1992

Maculopathy caused by intra-arterially administered cisplatin and intravenously administered carmustine.

Eight patients with malignant gliomas were monitored with clinical examinations to study the effects of the combination of intravenous administration of carmustine and infraophthalmic intra-arterial administration of cisplatin on retinal and optic nerve function. Three patients developed a severe macular retinal pigment abnormality in the eye ipsilateral to the intra-arterial infusion. Electrophysiologic studies disclosed no evidence of a generalized disturbance in the photoreceptors, middle retinal layers, or retinal pigment epithelium. In contrast to previous studies involving patients whose visual loss was caused by vaso-occlusive lesions in the retina and optic nerve, our study involved patients with clinically significant maculopathy, that was not vascular in origin and that developed after treatment with carmustine and cisplatin. We suggest that the deficit may result from a localized retinal pigment disturbance in the macula.

Adult↗
PubMed1990

Hue discrimination and S cone pathway sensitivity in early diabetic retinopathy.

Measures of hue discrimination and M (green) and S (blue) cone pathway sensitivities were compared in a group of 24 diabetics with either early background retinopathy or no retinopathy. The Farnsworth-Munsell 100-hue test was used to measure hue discrimination, and a two-color increment threshold technique was used to measure S and M cone pathway sensitivities. The results were compared to the level of diabetic retinopathy, to the degree of macular edema, and to the duration of the disease. No significant correlation was found between the Farnsworth-Munsell 100-hue error scores and the level of retinopathy; S cone pathway sensitivity loss, however, correlated significantly with both the level of retinopathy and the degree of macular edema. Our results indicate that measurements of S cone pathway sensitivity using an increment threshold technique provide a more sensitive method than hue discrimination for detecting color vision deficits in early diabetic retinopathy.

Adult↗
PubMedDate not supplied

The neurobiological basis of reading.

The results from studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) in adults have largely revealed the involvement of left-hemisphere perisylvian areas in the reading process, including extrastriate visual cortex, inferior parietal regions, superior temporal gyrus, and inferior frontal cortex. Although the recruitment of these regions varies with the particular reading-related task, general networks of regions seem to be uniquely associated with different components of the reading process. For example, visual word form processing is associated with occipital and occipitotemporal sites, whereas reading-relevant phonological processing has been associated with superior temporal, occipitotemporal and inferior frontal sites of the left hemisphere. Such findings are evaluated in light of the technical and experimental limitations encountered in functional brain imaging studies, and the implications for pediatric studies are discussed.

Brain Mapping↗