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Biomedical subjects

K Latham

Publications and source records attributed to K Latham.

At least 19 recordsLinked to original sources
PubMed2005

Application of numerical basis sets to hydrogen bonded systems: a density functional theory study.

We have investigated and compared the ability of numerical and Gaussian-type basis sets to accurately describe the geometries and binding energies of a selection of hydrogen bonded systems that are well studied theoretically and experimentally. The numerical basis sets produced accurate results for geometric parameters but tended to overestimate binding energies. However, a comparison of the time taken to optimize phosphinic acid dimer, the largest complex considered in this study, shows that calculations using numerical basis sets offer a definitive advantage where geometry optimization of large systems is required.

Journal Article↗
PubMed2000

A screen of random sequences for those that alter the trafficking of the influenza virus hemagglutinin in vivo.

In order to determine if the sequence patterns known to specify internalization represent the majority of possible internalization signals, we identified random sequences capable of causing a reporter protein to be internalized at least several-fold faster than the rate of non-selective internalization of membrane by clathrin-coated pits. A library of influenza hemagglutinin (HA) proteins, bearing short random sequences in place of the wild-type cytoplasmic domain, was prepared in recombinant SV40 virus. The library was expressed and screened for HAs that could internalize anti-HA antibody from the medium. The cytoplasmic sequences of the selected proteins were determined. From a small sample of sequences we detected several that did not resemble those previously identified. The known internalization signals must represent only a subset of the sequences that can serve as internalization signals.

Amino Acid Motifs↗
PubMed1998

Mash2 is expressed in oogenesis and preimplantation development but is not required for blastocyst formation.

The basic helix-loop-helix transcription factor, Mash2, has been shown to be necessary for the development of the spongiotrophoblast of the mature chorioallantoic placenta of the mouse. Here we show that Mash2 is transcribed during oogenesis and expressed throughout preimplantation development, only becoming restricted to the diploid trophoblast around the time of implantation. This expression raised the possibility that Mash2 has earlier functions in the trophoblast lineage that were not detectable in mutant embryos because of the persistence of oogenetically derived protein. This was tested by generating viable Mash2-/- females by tetraploid rescue of the extraembryonic defect. Mutant embryos derived from such females showed no enhanced phenotype over embryos produced from heterozygous females, demonstrating unequivocally that neither maternal nor zygotic Mash2 is required for early trophoblast development. If Mash2 functions in other aspects of trophoblast development, it must act cooperatively with other factors.

Animals↗
PubMed1998

No effect of age on spatial interval discrimination as a function of eccentricity or separation.

PURPOSE: Performance on positional acuity tasks exhibits marked resistance to the effects of optical image degradation. This places positional acuity tasks in a unique position for psychophysical examination of the effects of age upon visual performance because any observed age-related changes reflect losses in retinal/neural function. One positional acuity task with important consequences for "real-world" vision is spatial interval discrimination, a task in which the subject is required to detect changes in the size of the gap between two objects. In the present study we examine spatial interval discrimination in young and elderly observers as a function of separation and eccentricity. METHODS: Stimuli were two Gaussian-modulated luminance patches placed side by side around an imaginary iso-eccentric arc in the upper visual field, allowing eccentricity and separation to be varied independently. Changes in separation were achieved by moving the stimuli around the arc, while eccentricity was varied by changing the radius of the arc. Thresholds were obtained for healthy young and elderly observers using a forced-choice method of constants at two eccentricities (1.25 degrees and 10 degrees) and five separations. RESULTS: When thresholds, expressed as Weber fractions, are plotted as a function of the geometric ratio of the stimuli (separation/eccentricity) the data from the young and elderly groups collapse to a single function. Performance is independent of age and eccentricity, and depends only on the geometric ratio of the stimuli. CONCLUSIONS: No effect of age was found for spatial interval discrimination. Our results suggest that spatial interval discrimination belongs to the wider group of positional acuities whose neural substrates are unaffected by ageing.

Adult↗
PubMed1997

Disentangling the role of spatial scale, separation and eccentricity in Weber's law for position.

Factors underlying Weber's law for position were investigated by measuring spatial interval discrimination accuracy for spectrally narrow-band stimuli. These stimuli were positioned around an iso-eccentric arc in order to allow separation and eccentricity to be varied independently. We find that Weber's law occurs at individual spatial scales, and holds true not just for stimuli positioned either side of fixation, but for any series of stimuli which possess the same ratio of separation to eccentricity. When the separation/eccentricity ratio is large, thresholds are proportional to eccentricity and demonstrate contrast independence. At smaller separation/ eccentricity ratios, thresholds are determined by a contrast-dependent combination of separation and eccentricity.

Contrast Sensitivity↗
PubMed1997

Patterns of cataract referral in the West Midlands.

Optometrists are required to refer patients with any abnormality of the eye, excluding normal changes due to age, to a General Practitioner. It can be difficult to decide when a cataract ceases to be a normal age-related change and becomes an ocular abnormality. This questionnaire-based study examines the criteria adopted by Optometrists and GPs for referring patients with cataract and compares this to the referral criteria suggested by Ophthalmologists. For all professions, the main factors influencing referral are visual acuity, subjective visual impairment and the need to drive. Optometrists and GPs generally refer patients with cataract at a VA level of 6/18-6/24, whilst most Ophthalmologists would be willing to see patients with cataract at a VA of 6/9-6/12. However, Ophthalmologists report that sometimes patients are referred too soon, regardless of their acuity level, because the patient is not yet impaired by their level of vision or does not want surgery. Suggestions for improvements in the referral of cataract are discussed. It is important for Optometrists to make clear whether a letter to a GP is for information only or for referral. If referral is warranted, information in addition to acuity will assist an Ophthalmologist in prioritizing appointments, including age, occupation, brief description of disability and the need to drive without contravening any laws.

Adult↗
PubMed1996

A comparison of word recognition and reading performance in foveal and peripheral vision.

Word recognition thresholds and rapid serial visual presentation (RSVP) reading rates for both unrelated words and meaningful sentences were examined across the visual field. Both word recognition thresholds and RSVP reading rates for unrelated words can be equated across the visual field by an increase in size scale. RSVP reading rates for meaningful sentences cannot be equated across the visual field, with the fovea demonstrating a qualitative superiority over the periphery, irrespective of scale. The results suggest that the early visual machinery which underlies word recognition is the same across the visual field apart from a change in scale, whilst the periphery is qualitatively inferior to the fovea at interpreting sentences with meaning.

Adult↗
PubMed1996

Relative roles of resolution and spatial interference in foveal and peripheral vision.

The rate of change of visual performance with increasing eccentricity of fixation is known to be task dependent. In order to examine eccentricity-related changes in visual performance when a combination of two different factors influence thresholds, visual acuity in the presence of flanking elements was investigated across the visual field. Interference zones increased in extent with eccentricity at a much faster rate than did resolution thresholds. E2 values, quantifying the eccentricity-related magnification required, were 1-2 degrees for resolution and 0.1-0.2 degrees for spatial interference. E2 values for resolution in the presence of flanks depended on the proximity of the flanks and their 'weighting' in the task. From the results, the magnitude and extent of spatial interference across the visual field can be described quantitatively. Further, the results serve as an example of how observed variations in peripheral threshold gradients might be achieved as a combination of underlying factors with different E2 values.

Data Interpretation, Statistical↗
PubMed1995

A redrawn Vandenberg and Kuse mental rotations test: different versions and factors that affect performance.

The available versions of the Vandenberg and Kuse (1978) Mental Rotations Test (MRT) have physically deteriorated because only copies of copies are available. We report results from a redrawn version of the MRT and for alternate versions of the test. Males perform better than females, and students drawn from the physical sciences perform better than students drawn from the social sciences and humanities, confirming other reports with the original version of the MRT. Subjects find it very hard to perform the MRT when stimuli require rotation along both the top/bottom axis and the left/right axis. The magnitude of effect sizes for sex (which account, on average, for some 20% of the variance) does not increase with increasing difficulty of the task. Minimal strategy effects were observed and females did not perform differently during the menstrual period as opposed to the days between the menstrual periods. Practice effects are dramatic, confirming other reports with the original MRT, and can also be shown to be powerful in a transfer for practice paradigm, where test and retest involve different versions of the MRT. Main effects of handedness on MRT performance were not found.

Adult↗
PubMed1994

Spatial summation of the differential light threshold as a function of visual field location and age.

Static differential light thresholds were measured as a function of stimulus size (Goldmann sizes I-V) along four visual field meridia (75, 165, 255 and 345 degrees) with the Humphrey Field Analyzer 640. Data were obtained for both young (n = 10, age 23.6 +/- 2.9 years) and elderly (n = 10, age 72.0 +/- 5.2 years) normal subjects. The resulting peripheral spatial summation curves could be equated to the foveal data simply by a change in size scale, which increased linearly with eccentricity. E2 values, expressing the eccentricity at which stimulus size must double for performance to remain comparable to the fovea, were in the order of 3-9 degrees. Whilst the rate of scale change is approximately the same for both young and elderly observers, differences in performance can be explained by a combination of lower sensitivity and a bias in sensitivity towards larger stimulus sizes with increasing age.

Adult↗
PubMed1994

Murine A-myb: evidence for differential splicing and tissue-specific expression.

The myb gene family consists of three members, A-myb, B-myb and c-myb. The proteins encoded by these genes bind DNA in a sequence-specific manner and regulate transcription of target genes. In this communication, we report the nucleotide sequence of murine A-myb cDNA. This gene encodes a protein of 751 amino acids with an estimated molecular weight of 83 kDa. cDNA sequence analysis of multiple independent cDNA clones reveals the presence of alternatively spliced mRNAs that encode smaller proteins. Northern blot analysis of adult mouse tissue RNAs reveals A-myb expression predominantly in the testis, with very low levels of expression in the ovaries, spleen and brain. In situ hybridization analysis of adult mouse testis shows that this gene is expressed at high levels in type A spermatogonia (stem cells), and preleptotene and pachytene spermatocytes, with concomitant down-regulation of expression upon terminal differentiation of these cells into mature spermatozoa. This pattern of expression suggests that A-myb is involved in the control of proliferation and differentiation of spermatogonia. This potential function of A-myb in spermatogenesis is reminiscent of the role of c-myb in hematopoiesis.

Amino Acid Sequence↗
PubMed1993

Detection and discrimination of curvature in foveal and peripheral vision.

Curvature detection and discrimination were measured across the visual field in order to determine whether performance at a given eccentricity could be related to that at another by a simple change of magnification. Both types of task obeyed this concept, the critical variable being the rate at which magnification must increase as a function of eccentricity. The situation can be expressed in terms of the eccentricity (E2) at which magnification must be doubled to retain performance equivalent to that at the fovea. E2 values were 1.84-1.96 deg for the detection task and 1.42-2.27 deg for discrimination. These are similar to E2 values for vernier acuity and orientation discrimination, suggesting that all of these tasks share a common determining feature across the visual field, perhaps the distribution of neural elements selective for stimulus orientation.

Discrimination, Psychological↗
PubMed1993

Magnification perimetry.

PURPOSE: The authors used a method of spatial scaling to quantify the eccentricity-related decline in differential light sensitivity as a function of visual field meridian and age. METHODS: Differential light threshold at the fovea was measured in two groups of subjects of differing age (young mean age, 23.6 yr; standard deviation, 2.4 yr; elderly mean age, 69.6 yr; standard deviation, 6.2 yr) using a Goldmann size I stimulus moving across fixation at 1 degree/sec. With luminance kept constant, eccentricity thresholds for kinetic stimuli of increasing magnification were then measured. The results were analyzed in terms of the E2 value, which specifies the eccentricity at which the stimulus size must double to maintain performance equivalent to that at the fovea. RESULTS: For the young subjects, eccentricity thresholds increased linearly with an increase in stimulus diameter for most meridians. E2 varied between 5-12 degrees, depending on the meridian, and showed the same meridional trend as that of retinal ganglion cell distribution, although the magnitudes of E2 were different. For the elderly subjects, the eccentricity thresholds increased in a nonlinear manner with the stimulus diameter. CONCLUSIONS: Further factors, such as spatial summation, must also determine the eccentricity dependence of the differential light threshold because ganglion cell density decreases at a much faster rate than the differential light threshold. The most marked effects of age on differential light sensitivity occur at the fovea and beyond 20 degrees in the peripheral field, with a relative sparing in the pericentral area.

Adult↗
PubMed1992

The influence of eccentricity on position and movement acuities as revealed by spatial scaling.

The rate of decline with increasing eccentricity of several position and movement acuities was measured using a method of spatial scaling. In this method all stimuli at each visual field location are simply magnified versions of each other. The influence of separation and eccentricity were dissociated by presenting stimuli on an iso-eccentric arc. For each task, the rate of decline in performance was quantified by the parameter E2 which represents the eccentricity at which stimulus size must double in order to maintain performance equivalent to that at the fovea. All tasks were found to obey the concept of spatial scaling in that performance at a given field location could be equated with performance at any other location simply by a change of scale. However, the rate at which performance deteriorated with eccentricity varied over an enormous range (over 100-fold) depending on the task itself. The advantage of such diverse peripheral gradients is clear; the goal is to establish the physiological mechanisms which underlie this phenomenon.

Discrimination, Psychological↗
PubMed1987

Cytostatic and cytotoxic activity of tumor necrosis factor on human cancer cells.

The cytostatic and cytotoxic activity of human recombinant tumor necrosis factor (rTNF) was assayed on different tumor cell lines. Human BT-20 breast and ME-180 cervix cancer cells were growth-inhibited by rTNF, whereas two other cell lines were not significantly inhibited. However, when protein synthesis was inhibited by cycloheximide, rTNF was cytotoxic for these cells but not for BT-20 cells. This finding suggested that different mechanisms are responsible for the cytostatic and cytotoxic activity of rTNF. The sensitivity of different cell lines to rTNF could not be correlated with a high number or affinity of rTNF receptors. Occupancy of only a few receptors was sufficient for rTNA cytotoxicity, but an increase in receptor number after treatment with interferon-gamma, or a decrease after pretreatment with cycloheximide, correspondingly enhanced or depressed the cytotoxicity of rTNF. It seemed possible that some cells could be protected from this effect of rTNF by synthesizing "protective" proteins. While searching for such proteins, we observed that rTNF induced the synthesis of two polypeptides in SK-MEL-109 melanoma cells, but not in other cancer cells. Actinomycin D added with rTNF abolished synthesis of these polypeptides, suggesting that rTNF induced transcription of the corresponding mRNAs. Surprisingly, rTNF stimulated growth of SK-MEL-109 cells cultured in medium with low serum.

Breast Neoplasms↗
PubMed1987

Cytocidal activity of tumour necrosis factor: protection by protease inhibitors.

The mechanism of the cytostatic and cytocidal activities of TNF was studied in human tumour cells. BT-20 breast and ME-180 cervical cancer cells were significantly growth-inhibited by TNF, but other cells were not. When protein synthesis was inhibited by cycloheximide, however, TNF was cytotoxic for all cells except BT-20 cells. This suggests that different mechanisms are responsible for the cytostatic and cytocidal activities of TNF. The sensitivity of different cell lines could not be correlated with the number or affinity of TNF receptors. Some protease inhibitors completely protected human and murine cells from TNF cytotoxicity. Inhibitors of chymotrypsin-like proteases were more effective than inhibitors of trypsin-like proteases. Reversible and irreversible inhibitors (such as alkylating compounds) were both protective. The cells were best protected when pretreated with inhibitors before the addition of TNF. When the protease inhibitors were removed the cells gradually lost their resistance to TNF cytotoxicity. The inhibitors did not interfere with the functioning of TNF-receptor complexes, since SK-MEL-109 melanoma cells treated with a protease inhibitor synthesized TNF-induced proteins. These findings suggest that a protease is involved in the cytocidal activity of TNF.

Humans↗
PubMed1985

Beta receptors in peripheral mononuclear cells increase acutely during exercise.

Five healthy adult well trained men (averaging 49 miles running per week) were exercised to exhaustion on a treadmill. Plasma epinephrine increased from 168 +/- 37 pg/ml prior to exercise to 633 +/- 155 pg/ml immediately after exercise (P less than 0.025) and plasma norepinephrine increased from 1608 +/- 345 to 8576 +/- 1662 pg/ml (P less than 0.025) in the two respective periods. Beta receptor density increased from 53 +/- 18 fmol/mg protein before exercise, to 223 +/- 63 fmol/mg (P less than 0.05) protein immediately after exercise, and then decreased to 83 +/- 27 fmol/mg protein 1 h later (P less than 0.05 compared to post-exercise). The mean Kd value prior to exercise of 1.5 +/- 0.2 X 10(-11) M was unchanged statistically throughout the study. Following correction for haemodilution, serum total and free T4 and T3 concentrations were also unchanged during exercise, although reverse T3 levels did increase from 39 +/- 4 to 45 +/- 0 ng/dl (P less than 0.05). These findings suggest that: 1) plasma epinephrine, norepinephrine and beta receptor density, but not Kd, increase acutely during exercise and 2) total and free T4 and T3, after correction for haemodilution, do not change during acute exercise. Our data indicate that acute exercise represents an unusual condition during which 'down regulation' is not observed, but, rather, there appear to be parallel alterations in beta receptor density and plasma catecholamine levels.

Adult↗