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J C Ingram

Publications and source records attributed to J C Ingram.

At least 19 recordsLinked to original sources
PubMed2001

Topology of a human equilibrative, nitrobenzylthioinosine (NBMPR)-sensitive nucleoside transporter (hENT1) implicated in the cellular uptake of adenosine and anti-cancer drugs.

The human equilibrative nucleoside transporter hENT1, the first identified member of the ENT family of integral membrane proteins, is the primary mechanism for the cellular uptake of physiologic nucleosides, including adenosine, and many anti-cancer nucleoside drugs. We have produced recombinant hENT1 in Xenopus oocytes and used native and engineered N-glycosylation sites in combination with immunological approaches to experimentally define the membrane architecture of this prototypic nucleoside transporter. hENT1 (456 amino acid residues) is shown to contain 11 transmembrane helical segments with an amino terminus that is intracellular and a carboxyl terminus that is extracellular. Transmembrane helices are linked by short hydrophilic regions, except for a large glycosylated extracellular loop between transmembrane helices 1 and 2 and a large central cytoplasmic loop between transmembrane helices 6 and 7. Sequence analyses suggest that this membrane topology is common to all mammalian, insect, nematode, protozoan, yeast, and plant members of the ENT protein family.

Adenosine↗
PubMed2001

Subcellular distribution and membrane topology of the mammalian concentrative Na+-nucleoside cotransporter rCNT1.

The rat transporter rCNT1 is the archetype of a family of concentrative nucleoside transporters (CNTs) found both in eukaryotes and in prokaryotes. In the present study we have used antibodies to investigate the subcellular distribution and membrane topology of this protein. rCNT1 was found to be expressed predominantly in the brush-border membranes of the polarized epithelial cells of rat jejunum and renal cortical tubules and in the bile canalicular membranes of liver parenchymal cells, consistent with roles in the absorption of dietary nucleosides, of nucleosides in the glomerular filtrate, or of nucleosides arising from the action of extracellular nucleotidases, respectively. The effect of endoglycosidase F treatment on wild-type and mutant rCNT1 expressed in Xenopus oocytes revealed that the recombinant transporter could be glycosylated at either or both of Asn605 and Asn643, indicating that its C terminus is extracellular. In contrast, potential N-glycosylation sites introduced near the N terminus, or between putative transmembrane (TM) helices 4 and 5, were not glycosylated. The deduced orientation of the N terminus in the cytoplasm was confirmed by immunocytochemistry on intact and saponin-permeabilized Chinese hamster ovary cells expressing recombinant rCNT1. These results, in conjunction with extensive analyses of CNT family protein sequences using predictive algorithms, lead us to propose a revised topological model, in which rCNT1 possesses 13 TM helices with the hydrophilic N-terminal and C-terminal domains on the cytoplasmic and extracellular sides of the membrane, respectively. Furthermore, we show that the first three TM helices, which are absent from prokaryote CNTs, are not essential for transporter function; truncated proteins lacking these helices, derived either from rCNT1 or from its human homolog hCNT1, were found to retain significant sodium-dependent uridine transport activity when expressed in oocytes.

Amino Acid Motifs↗
PubMed2001

Semantic priming in Alzheimer's dementia: evidence for dissociation of automatic and attentional processes.

The nature of the semantic memory deficit in dementia of the Alzheimer's type (DAT) was investigated in a semantic priming task which was designed to assess both automatic and attention-induced priming effects. Ten DAT patients and 10 age-matched control subjects completed a word naming semantic priming task in which both relatedness proportion (RP) and stimulus-onset asynchrony (SOA) were varied. A clear dissociation between automatic and attentional priming effects in both groups was demonstrated; however, the DAT subjects' pattern of priming deviated significantly from that of the normal controls. The DAT patients failed to produce any priming under conditions which encouraged automatic semantic processing and produced facilitation only when the RP was high. In addition, the DAT group produced hyperpriming, with significantly larger facilitation effects than the control group. These results suggest an impairment of automatic spreading activation in DAT and have implications for theories of semantic memory impairment in DAT as well as models of normal priming.

Aged↗
PubMed2001

Hyperosmotic shock induces both activation and translocation of glucose transporters in mammalian cells.

The effect of osmotic stress on sugar transport was investigated in Clone 9 epithelial cells, which express the glucose uniporter GLUT1, and in 3T3-L1 adipocytes, which express both GLUT1 and GLUT4. An acute hyperosmotic shock increased the uptake of sugars in both cell types. In Clone 9 cells, this was followed by a regulatory volume increase (RVI) response. Stimulation of transport was rapid and reversible, with half-lives (t 1/2) for stimulation of 2-deoxy-D-glucose uptake of 5.6 +/- 0.9 (n=6) and 22.7 +/- 1.5 (n=4) min for Clone 9 cells and adipocytes respectively. The effect was dose dependent, reaching a maximum at 1.1 osM of 2.9 +/- 0.1-fold (n=3) for Clone 9 cells and 8.2 +/- 0.8-fold (n=3) for adipocytes. In the latter, this stimulation correlated with translocation of the glucose transporter isoform GLUT4 to the cell surface and was not significantly different from that elicited by 160 nM insulin (7.6 +/- 1.2-fold, n=3). The effect of osmotic shock was not, however, influenced by inhibitors of either phosphoinositide 3-kinase (PI 3-kinase) (wortmannin, 250 nM) or of p38 mitogen-activated protein kinase (p38 MAP kinase) (SB203580, 20 microM), which reportedly prevent GLUT4 translocation and/or activation by insulin respectively. These inhibitors also had no effect on the stimulation of transport by osmotic shock in Clone 9 cells. However, in contrast to adipocytes, the effect of osmotic shock on glucose transport in Clone 9 cells reflected primarily a change in the intrinsic activity of cell surface transporters and there was only a minor change in their subcellular distribution as assessed by cell immunostaining or no change as assessed by surface biotinylation. These results indicate that the response of cells to osmotic shock can involve changes both in transporter activity and location. The signal transduction pathways involved include neither PI 3-kinase nor the classical, osmotically-activated component, p38 MAP kinase.

3T3 Cells↗
PubMed2000

Secondary ion mass spectrometric characterization of nail polishes and paint surfaces.

A variety of paint and fingernail polish samples, which were visually similar, but had different chemical compositions and formulations, was analyzed using quadrupole static secondary ion mass spectrometry (SIMS). Coating distinction was easily achieved in many cases because of the presence of dominant ions derived from the components of the coating, which could be observed in the SIMS spectra. In other instances, coating distinction was difficult within a product line because of spectral complexity; for this reason and because of the large numbers of spectra generated in this study, multivariate statistical techniques were employed, which allowed the meaningful classification and comparison of spectra. Partial Least Squares (PLS) and Principal Component Analysis (PCA) were applied to quadrupole SIMS data. PCA showed distinct spectral differences between most spectral groups, and also emphasized the reproducibility of the SIMS spectra. When using PLS analysis, reasonably accurate coating identification was achieved with the data. Overall, the PLS model is more than 90% effective in identifying the spectrum of a particular coating, and nearly 100% effective at telling which coating components represented in the PLS models are not present in a spectrum. The level of spectral variation caused by sample bombardment in the SIMS analysis was investigated using Fourier transform infrared spectroscopy (FT-IR) and quadrupole static SIMS. Changes in the FT-IR spectra were observed and were most likely a result of a number of factors involving the static SIMS analysis. However, the bulk of the sample is unaltered and may be used for further testing.

Cosmetics↗
PubMed1999

Maternal predictors of early breast milk output.

Previous attempts to show a quantitative relationship between maternal hormone levels and early milk output have used small sample sizes and simple correlations. Women of mixed parity and similar socio-economic status and education were recruited to a study using multivariate analysis to look for these associations. Hormone levels (oestradiol, progesterone, prolactin and thyrotropin (TSH)) were determined for 91 mothers at four time points (ante- and postnatally) from finger-prick blood spots by fluoro-immunoassay. Milk output at 1 and 4 weeks was determined from 24-h test weighings. Parity was found to be the most significant factor affecting breast milk volume at 1 wk postpartum (multiparous women delivered 142 ml more milk in 24 h than primiparous women). Total time spent feeding had a strong association with breast milk volume, with increasing time having a negative effect. Multiple regression analysis, controlling for parity and time spent feeding, showed a positive association of milk output at 1 wk with antenatal progesterone and antenatal prolactin levels. At 4 wk, higher postpartum oestradiol levels had a negative association and antenatal progesterone levels a positive association with milk output. This study demonstrates that there are quantitative associations between antenatal maternal hormone levels and breast milk output in the early postnatal period.

Adult↗
PubMed1998

Language, context, and speaker effects in the identification and discrimination of English /r/ and /l/ by Japanese and Korean listeners.

Japanese and Korean listeners' identification and discrimination of English /r/ and /l/ were compared using a common set of minimal pair stimuli. The effects of speakers (two native speakers of Australian English), position of the contrast within the word (word initial, initial consonant cluster. and medial positions), and listening task (forced choice identification versus oddball discrimination) were examined, with a view to assessing the relative importance of language-specific and language-independent factors operating at the acoustic-phonetic and phonological levels of signal processing in "foreign sound" speech perception. Both prior phonological learning and the relative acoustic discriminability of the items affected subjects' performance on the identification test. Where both factors were engaged, phonological learning effects predominated over the effects of acoustic discriminability. The extent to which a speaker encoded critical acoustic cues for the /r-l/ distinction was found to affect /r-l/ identification. Dynamic spectral features known to be relevant for the /r-l/ contrast were effective in predicting (in a linear regression analysis) speaker-dependent differences in identification scores. Although the discrimination test may have been influenced by ceiling effects, the performance profiles on the identification and discrimination tests were quite different, indicating that the identification and discrimination tests imposed quite different task demands upon listeners and that phonological processing of the signal was more engaged by the former task.

Adolescent↗
PubMed1994

The effect of repeated prime-target presentation in manipulating attention-induced priming in persons with dementia of the Alzheimer's type.

The present experiment manipulated attention-induced semantic priming in seven persons with dementia of the Alzheimer's type (DAT) and 16 healthy aged controls in a word-nonword lexical decision task by means of repeated prime-target presentations. The experimental paradigm allowed for the simultaneous comparison of automatic processing and attention-induced strategic processing. The results showed that both the healthy aged subjects and the subjects with DAT demonstrated semantic facilitation in the automatic processing of information. The two groups differed, however, on the attention-induced component of the task. The control subjects consciously generated a strategic response bias favoring the real word targets and thus used their processing of the prime to induce an expectancy about the following target. The DAT subjects showed no such attention-dependent expectancy, a deficit which is most probably related to the general cognitive impairments which are a hallmark of the disease.

Aged↗
PubMed1993

Nursing and medical staffing in neonatal units.

Organizational aspects of neonatal care were documented in a large scale national survey: these included the provision of cots, the nursing establishment, medical staffing and the use of nurses qualified in the specialty. Fifty-six unidentified neonatal units in England were contacted and information requested on staffing arrangements, policies and facilities. To gain an accurate picture, four representative units were selected in each health region: a regional centre, a sub-regional centre and two district units. Comparisons were made using data on cot provision, the nursing establishment set, the numbers of trained nurses and medical staffing in the target units. Large inter-unit differences were found and in many units the levels of staffing were found to be at lower levels than those recommended. The relationship between the nursing establishment and numbers of designated cots was examined using different models of staffing based on successive recommendations. The more recent the recommendation, the greater the discrepancy between the establishment in operation and that recommended. Large inter-unit variation was also found in the proportion of staff qualified in the specialty, ranging from 0% to 92% of qualified nurses in individual units. Overall 1544 (83%) trained nurses were working in the study units, of whom 820 (53%) were qualified in the specialty. Significant differences were found between the types of unit: regional and sub-regional units had a higher 'Qualified in Specialty' rate (50% and 49%) than district units (32%).(ABSTRACT TRUNCATED AT 250 WORDS)

England↗
PubMed1990

Do changes in pattern of breast usage alter the baby's nutrient intake?

Twelve mother/baby pairs took part in a study of the difference in effect of two patterns of breast feeding--either feeding at one breast or at two breasts during a feed. Baseline measures were taken at 4 weeks, and the test patterns of feeding were followed for a week each, in random order. The two patterns of feeding led to differences in milk volume intake and mean feed fat concentration, but not in the baby's net fat intake per 24 h. The results indicate that the breast-fed baby can regulate his fat intake quickly and thus mothers should be encouraged to practice "baby-led" feeding.

Breast Feeding↗
PubMed1990

Automatic and volitional semantic processing in aphasia.

The present study investigated the status of semantic information in aphasia by comparing the performances of aphasic and nonaphasic subjects on two tasks: an automatic semantic facilitation task and a volitional task of relatedness judgment. Both the aphasic and nonaphasic groups evidenced a semantic facilitation effect, in an on-line task of semantic processing. However, those aphasics with severe comprehension and naming disturbances (termed low comprehension aphasics) demonstrated considerable difficulty in judging the relatedness between a pictured object and members of that object's semantic field, the severity of the impairment being greater for those pictures that the low comprehension aphasics were unable to name. The pattern of results can best be explained by supposing the structural integrity of the store of semantic information in aphasia, and in particular in low comprehension aphasia: information that is retrieved and manipulated in judgment-mediated tasks with considerable difficulty.

Adult↗
PubMed1989

Respiratory function in Parkinson's subjects exhibiting a perceptible speech deficit: a kinematic and spirometric analysis.

The respiratory abilities of a group of 19 speech-disordered subjects with idiopathic Parkinson's disease were assessed using both spirometric and kinematic techniques and compared to those of a group of 19 nonneurologically impaired controls matched for age and sex. Results of the spirometric assessment showed that only a minority of the Parkinson's subjects had lung volumes and capacities outside normal limits. Consequently in the majority of cases, the speech disorder could not be related to any abnormality in lung function determined spirometrically. Chest wall dynamics during both conversation and reading were essentially normal in all cases. Approximately half of the Parkinson's subjects, however, exhibited irregularities in their chest wall movements while performing vowel prolongation and syllable repetition tasks. The same irregularities were not present in the chest wall movements exhibited by the control subjects, suggesting that their presence was in some way related to the Parkinson's disease. Results are discussed in terms of the effects of Parkinson's disease on neuromuscular function.

Aged↗
PubMed1985

Recidivism, perceived problem-solving abilities, MMPI characteristics, and violence: a study of black and white incarcerated male adult offenders.

This study examined recidivism, perceived problem-solving abilities, type of offense, and personality characteristics in an incarcerated male population. Twenty black males and 32 white males were selected systematically from inmate populations. The MMPI, its special scales, and the PSI scales were analyzed; F, L, Re, and Do scales reported significant results. Recidivists scored significantly higher than nonrecidivists on the impulsive scale of the Problem Solving Inventory. Black recidivists generated significantly higher scores on the F scale than did black or white nonrecidivists. The Pd scale reported a significant main effect for type of offense (p less than .05). Offenders incarcerated for violent crimes scored higher on the Pd scale than the nonviolent criminals. This research study demonstrated the utility of the MMPI and the PSI in discriminating between nonviolent and violent criminals.

Adult↗
PubMed1982

Language analysis in schizophrenia: diagnostic implications.

Language profiles were developed for schizophrenic, manic and nonpsychotic control subjects from the analysis of free speech samples. The profiles comprised syntactic variables reflecting the complexity, integrity and fluency of spoken language. Linguistic differences between the 3 diagnostic groups enabled accurate (95%) classification by discriminant function analysis. The results suggest an important role for language analysis in psychiatric diagnosis.

Adolescent↗