Biomedical subjects
N Cowan
Publications and source records attributed to N Cowan.
Process formation in Sf9 cells induced by the expression of a microtubule-associated protein 2C-like construct.
To understand the roles of various microtubule-associated proteins (MAPs) in the development of axons and dendrites, we have expressed individual neuronal MAPs in normally rounded Sf9 host cells. We previously reported that expression of tau protein in these cells results in the elaboration of long processes containing dense bundles of microtubules (MTs). These bundles generally terminate in the hillock region of the cell body, and almost all of the MTs within the bundles are oriented with their plus ends distal to the cell body. Here we report the expression of a construct that approximates the MAP2C sequence and also induces the elaboration of processes with dense bundles of predominantly plus-end-distal MTs. Whereas tau generally results in a single process, there is a significantly greater tendency for the MAP2C-like construct to induce multiple processes. In contrast to the tau processes, the MT bundle in these processes extends far into the cell body. This latter observation suggests that MAP2C and tau have different effects on MT assembly and/or transport events in the cell. Although both of these MAPs can organize MTs that are competent to participate in process formation, the detailed organization of MTs induced by each of the two constructs is distinctive, and these differences may be relevant to axonal and dendritic differentiation.
Memory prerequisites of mismatch negativity in the auditory event-related potential (ERP).
The mismatch negativity (MMN) is a component of the auditory event-related brain potential that occurs in response to infrequent changes in the physical properties of homogeneous series of sounds, even when subjects are instructed to ignore the auditory channel of stimulation. It has been proposed (e.g., Näätänen, 1990) that the MMN is generated by an automatic process in which a difference between the deviant sound and the previous, standard sound is detected by the brain. However, it is unclear how the form of memory involved is related to the rest of the memory system. The present study indicates that, for an MMN to be elicited in response to a change in tone frequency, the representation of the standard tone must be both (a) well-established as a standard in memory, and (b) in a currently active state. The relation between physiological and psychological aspects of memory representation is discussed.
Information processing models: microscopes of the mind.
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Activation, attention, and short-term memory.
The premise of this paper is that the popular term "short-term memory" (STM) is vague because it is used to refer to either (1) the set of representations from long-term memory currently in a state of heightened activation or (2) the focus of attention or content of awareness. A more coherent conception of STM is hierarchical, with the focus of attention depicted as a subset of the activated portion of long-term memory. Research issues are discussed to illustrate that this simple conception of STM leads to testable predictions and useful lines of inquiry.
Arteriovenous fistulas in renal transplants: color Doppler ultrasound observations.
One hundred twenty-six new renal transplants were scanned regularly with color Doppler ultrasound (CDU). In 22 (17.5%) of the grafts there was evidence of postbiopsy arteriovenous (AV) fistula during the first 6 months postoperatively. In 14 cases the fistula closed spontaneously. In the remaining eight, the fistula was still present up to 24 months later (four cases) or until the graft failed (four cases). Additionally, 163 established grafts were scanned for evidence of vascular abnormality. AV fistulas were observed in 15 grafts (8%). Circulatory complications of fistulas observed include vascular steal and a possible association with graft vein and artery stenosis.
The natural history of sciatica associated with disc pathology. A prospective study with clinical and independent radiologic follow-up.
The purpose of this study was to assess the natural history of sciatica due to lumbosacral nerve root compromise and to evaluate the pathomorphologic changes that accompany the natural resolution of the disease. One hundred sixty-five consecutive patients, 114 males and 51 females, with an average age of 41 years (range, 17-72) and an average duration of symptoms of 4.2 months (range, 1-72) presenting with sciatica thought to be due to lumbosacral nerve root compromise were admitted to the study. The cornerstone of treatment was the serial epidural administration of steroid and local anesthetic by the caudal route on an outpatient basis. Lumbar epidural injection or periradicular infiltration at the appropriate level, confirmed under image intensifier, was the next step before considering surgical decompression. An average of three injections (range, 0-8) was received by each patient. Patients underwent clinical examination and computed tomography. Twenty-three patients (14%) underwent surgical decompression. The remainder were clinically assessed at 1 year after presentation, and 111 were rescanned at the appropriate levels. All conservatively managed patients made a satisfactory clinical recovery: average reduction of pain on the visual analog scale was 94% (range, 45-100), and 64 (76%) of the 84 disc herniations and 7 (26%) of the 27 disc bulges showed partial or complete resolution (chi-square = 20.27, P = 0.0001). Thus a high proportion of patients with discogenic sciatica make a satisfactory recovery with aggressive conservative management, and this recovery is accompanied by resolution of disc herniations in a significant number. Only a small proportion of patients needed surgical decompression.
Recurrent speech patterns as cues to the segmentation of multisyllabic sequences.
First and second language acquisition both require that speech be segmented into familiar, multiphonemic units (e.g., words and common phrases). The present research examines one segmentation cue that is of considerable theoretical interest: the repetition of fixed sequences of speech. On each trial, subjects heard repetitions ('pre-exposures') of two artificially-constructed, multisyllabic patterns that shared an embedded segment 1 or 2 syllables long (e.g., 2 shared syllables: [ga-li-SE] and [li-SE-stu]). There were 2 and 6, 4 and 4, or 6 and 2 repetitions of the two patterns, randomly ordered. Subjects were then to indicate the groupings they perceived within a subsequent, longer sequence containing both of the pre-exposed patterns (e.g., [ga-li-SE-stu]). Responses varied systematically with the size of the embedded segment, the repetition frequencies of the two pre-exposed patterns, and the serial position of each pre-exposure. The results illustrate how investigations of the processing of speech patterns may contribute to an understanding of some elementary aspects of language learning.
Enhancement of 4-year-old children's memory span for phonologically similar and dissimilar word lists.
Previous research suggests that preschool children are deficient in rehearsal and that stimulus list repetitions can improve their recall, presumably by substituting for the products of rehearsal. However, the previous research included interitem or postlist retention intervals of several seconds or more. We examined the utility of list repetitions with reference to an ordinary span task in which spoken words were presented 1 s apart for immediate recall. Lists with phonologically similar versus dissimilar items were included, to determine if the overall pattern of recall could be made more similar to what is ordinarily obtained in older children. Cumulative repetition was found to cause a moderate increase in both memory span and the phonological similarity effect. Other types of list repetition provided more insight into types of stimulus redundancy that were helpful (e.g., repeated serial order information) or not helpful (e.g., forced articulatory coding) to children attempting to recall spoken lists. The underlying mnemonic processes are discussed.
Properties of memory for unattended spoken syllables.
Whereas previous studies on memory for unattended speech have inadvertently included acoustic interference, the present study examines memory for unattended syllables during a silent period of 1, 5, or 10 s. The primary task was to read silently (Experiments 1-3) or whisper the reading (Experiment 4). Occasionally, when a light cue occurred, the subject was to recall the most recent spoken syllable, as well as the recent reading material. Memory for both the vowels and consonants of the syllables decreased across 10 s, confirming that auditory memory does decay in the absence of acoustic interference. However, the specific patterns of memory decay for vowels versus consonants depended on task demands, including the allocation of attention and the opportunity for subvocal coding. We suggest an account of performance that includes auditory sensory and phonetic memory codes with different properties, used in combination.
Suffix interference in the recall of linguistically coherent speech.
Four experiments are presented that address the stimulus suffix effect for linguistically coherent spoken materials. In Experiment 1, definitions of low-frequency words were presented for online written recall. Each definition was followed by a nonword speech suffix presented in the same voice as the definition, the same nonword presented in a different voice, or a tone. The results yielded a significant reduction in the recall of the terminal words of the definitions in the speech suffix conditions compared with the tone control. This general pattern was replicated in Experiment 2, in which subjects did not begin their recall until the suffix item or tone was presented, although the magnitude of the suffix effect was reduced in this experiment. In Experiment 3, sentences that were part of a cohesive story were presented for on-line recall. Here, the suffix effect was considerably reduced compared with the suffix effect found with the definitions presented in Experiments 1 and 2. This pattern was replicated in Experiment 4, in which subjects did not begin their recall of the story sentences until the speech suffix or tone was presented. Overall, the results suggest that auditory memory interference can take place for linguistically coherent speech, although the magnitude of the interference decreases as one increases the level of linguistic structure in the to-be-recalled materials. Implications of the present results for current models of natural language processing are discussed.
Comparison of the hemodynamic effects of nitric oxide and endothelium-dependent vasodilators in intact lungs.
The effects of endothelium-dependent vasodilation on pulmonary vascular hemodynamics were evaluated in a variety of in vivo and in vitro models to determine 1) the comparability of the hemodynamic effects of acetylcholine (ACh), bradykinin (BK), nitric oxide (NO), and 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP), 2) whether methylene blue is a useful inhibitor of endothelium-dependent relaxing factor (EDRF) activity in vivo, and 3) the effect of monocrotaline-induced pulmonary hypertension on the responsiveness of the pulmonary vasculature to ACh. In isolated rat lungs, which were preconstricted with hypoxia, ACh, BK, NO, and 8-bromo-cGMP caused pulmonary vasodilation, which was not inhibited by maximum tolerable doses of methylene blue. Methylene blue did not inhibit EDRF activity in any model, despite causing increased pulmonary vascular tone and responsiveness to various constrictor agents. There were significant differences in the hemodynamic characteristics of ACh, BK, and NO. In the isolated lung, BK and NO caused transient decreases of hypoxic vasoconstriction, whereas ACh caused more prolonged vasodilation. Pretreatment of these lungs with NO did not significantly inhibit ACh-induced vasodilation but caused BK to produce vasoconstriction. Tachyphylaxis, which was agonist specific, developed with repeated administration of ACh or BK but not NO. Tachyphylaxis probably resulted from inhibition of the endothelium-dependent vasodilation pathway proximal to NO synthesis, because it could be overcome by exogenous NO. Pretreatment with 8-bromo-cGMP decreased hypoxic pulmonary vasoconstriction and, even when the hypoxic pressor response had largely recovered, subsequent doses of ACh and NO failed to cause vasodilation, although BK produced vasoconstriction. These findings are compatible with the existence of feedback inhibition of the endothelium-dependent relaxation by elevation of cGMP levels. Responsiveness to ACh was retained in lungs with severe monocrotaline-induced pulmonary hypertension. Many of these findings would not have been predicted based on in vitro studies and illustrate the importance for expanding studies of EDRF to in vivo and ex vivo models.
Acquisition of Pig Latin: a case study.
A boy's acquisition of Pig Latin was monitored throughout the year preceding first grade. Abilities underlying this game include the identification of words, deletion of the first syllabic onset (i.e. prevocalic consonants) of each word, blending of this onset and the suffix [ei] onto the word's end, and short-term memory for speech units. Performance improved over time as the underlying abilities developed. Meanwhile, various informative errors were made. Throughout most of the study, onsets that were correctly removed from a word's beginning were often added to its end incorrectly; unstressed function words were repeated intact and not transformed; and the first syllabic onset was overlooked when the syllable was unstressed. Because speech games like this one depend upon basic language skills, they can clarify aspects of ordinary language development.
The reality of cross-modal Stroop effects.
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The primary structure and heterogeneity of tau protein from mouse brain.
Tau protein is a family of microtubule binding proteins, heterogeneous in molecular weight, that are induced during neurite outgrowth and are found prominently in neurofibrillary tangles in Alzheimer's disease. The predicted amino acid sequences of two forms of tau protein from mouse brain were determined from complementary DNA clones. These forms are identical in their amino-terminal sequences but differ in their carboxyl-terminal domains. Both proteins contain repeated sequences that may be tubulin binding sites. The sequence suggests that tau is an elongated molecule with no extensive alpha-helical or beta-sheet domains. These complementary DNAs should enable the study of various functional domains of tau and the study of tau expression in normal and pathological states.
Evolving conceptions of memory storage, selective attention, and their mutual constraints within the human information-processing system.
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Isolation of a sequence encoding human cystatin C. Conservation of exon-intron structure between members of the cysteine proteinase inhibitors superfamily.
The human cystatin C gene was cloned using a synthetic oligonucleotide predicted from a portion of its amino-acid sequence. The nucleotide sequence of the restriction fragment hybridizing with the oligonucleotide confirms the existence of one exon encoding amino acids 56-93 of human cystatin C and its relationship to kininogens. However the deduced amino-acid sequence differs in one position from the sequence of the cystatin C fragment deposited as amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of icelandic origin.