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Biomedical subjects

M Hunter

Publications and source records attributed to M Hunter.

At least 37 records · Page 2Linked to original sources
PubMed2001

Biophysical effects of pore mutations of ROMK1.

Potassium channels are ubiquitous, being present in all living organisms. These proteins share common structural elements, which confer common functional features. In general, all K+ channels have a high selectivity for K+, and are blocked by cations of similar dimensions, such as Cs+ and Ba2+. Mutations in the pore region tend to lead to either the total loss of function or K+ selectivity. We have made mutations to one of the most highly conserved residues of the pore, glycine-143, of the inward rectifier ROMK1 (Kir1.1), and examined the resulting channel properties in the Xenopus oocyte expression system with a two-electrode voltage clamp. Mutations G143A and G143R resulted in failure to express functional channels. Co-injection of wild-type ROMK1 cRNA with these mutants led to rescue of channel function, which was different from wild-type ROMK1. In both mutants, the sensitivity to Ba2+ and Cs+ was increased, the rate of onset of block by Ba2+ was enhanced, and the selectivity to potassium was reduced. Whereas the crystallographic evidence shows that cations bind to the carbonyl backbone of the pore-lining residues, the present results indicate that the side chains of these amino acids, which face away from the pore lining, also affect permeation.

Animals↗
PubMed2001

WMS-III performance in patients with temporal lobe epilepsy: group differences and individual classification.

The utility of the WMS-III in detecting lateralized impairment was examined in a large sample of patients with temporal lobe epilepsy. Methods of analysis included evaluation of group means on the various indexes and subtest scores, the use of ROC curves, and an examination of Auditory-Visual Index discrepancy scores. In addition, performance on immediate and delayed indexes in the auditory and the visual modality was compared within each group. Of the WMS-III scores, the Auditory-Visual Delayed Index difference score appeared most sensitive to side of temporal dysfunction, although patient classification rates were not within an acceptable range to have clinical utility. The ability to predict laterality based on statistically significant index score differences was particularly weak for those with left temporal dysfunction. The use of unusually large discrepancies led to improved prediction, however, the rarity of such scores in this population limits their usefulness. Although the utility of the WMS-III in detecting laterality may be limited in preoperative cases, the WMS-III may still hold considerable promise as a measure of memory in documenting baseline performance and in detecting those that may be at risk following surgery.

Adult↗
PubMed2000

An intracellular ATP-activated, calcium-permeable conductance on the basolateral membrane of single renal proximal tubule cells isolated from Rana temporaria.

1. The following study describes the properties of a non-selective cation channel, which has a unit conductance below the resolving power of the single channel technique, located on the basolateral membrane of single proximal tubule cells isolated from frog kidney. The conductance was examined using cell-attached, inside-out and outside-out patches. Due to the small single channel magnitude, macroscopic patch currents were measured. 2. Addition of 2 mM ATP to the intracellular surface of excised patches activated an outwardly rectifying conductance (MCANS): outward (Gout) and inward (Gin) conductances increased by 46.8 +/- 6.7 and 11.6 +/- 2.1 pS, respectively (n = 29). MCANS was more selective for cations than anions, with a cation:anion selectivity ratio of 10.1 +/- 1.7 (n = 7), but did not discriminate between Na+ and K+. It was more selective for Ca2+ over Na+, with a Ca2+:Na+ selectivity ratio of 4. 49 +/- 0.69 (n = 7). 3. In cell-attached patches addition of 100 microM strophanthidin to the bath increased both Gout and Gin. However this increase in conductance was absent in the presence of Gd3+, which inhibits MCANS. 4. These data suggest that single proximal tubule cells isolated from frog kidney contain an ATP-activated, non-selective cation conductance. The conductance does not discriminate between Na+ and K+, but is more selective for Ca2+ over Na+. Considering the prevailing electrochemical gradients for these ions, functional activation of the conductance would be expected to lead to a rise in intracellular Ca2+. MCANS is linked to the activity of the Na+, K+-ATPase and may therefore provide a link between the ATPase and K+ channel activity in the basolateral membrane and form an integral part of the pump-leak mechanism in transporting epithelia.

Adenosine Triphosphate↗
PubMed2000

EEG as a measure of developmental changes in the chicken brain.

Scalp-applied recording electrodes were used to monitor changes in basal EEG patterns in chickens during posthatch development. Frequency spectra produced by Fast Fourier Transform show a biphasic morphology in all chickens with one peak at about 6 Hz and another at 26 Hz. Changes in the lower frequency band show progressive development and provide a possible index of brain development. Both amplitude and dominant frequency of the spectra decrease between Weeks 3 and 8 posthatch, reaching adult levels between Weeks 5 and 7. These results suggest that modifications of basal EEG reflect the widespread functional changes in neuronal circuits occurring in chicken during the "synapse maturation" period between 3 and 8 weeks' posthatch.

Age Factors↗
PubMed2000

An evaluation of the Faces Pain Scale with young children.

The psychometric characteristics of the Faces Pain Scale (FPS) were evaluated in three groups of preschool and school-aged children (3. 5-4.5; 4.5-5.5 and 5.5-6.5 years, respectively). The FPS was adequately comprehended by even young children. It was easily administered and was valid and discriminating. It did not, however, possess the linear scalability claimed by its authors.

Child↗
PubMed2000

Theory of mind and executive functions in normal human aging and Parkinson's disease.

Although the majority of research in theory of mind (TOM) has focused on young children or individuals with autism, recent investigations have begun to look at TOM throughout the lifespan and in other neurological and psychiatric populations. Some have suggested that TOM may represent a dissociable, modular brain system that is related to, but separable, from other brain functions including executive functions (EF). Recently, studies have shown that TOM performance can be compromised following an acquired brain insult (e.g., damage to the right hemisphere). However, the relationship of such impaired TOM performance to other brain functions in these cases has not been explored. This study investigated the effects of both normal human aging and Parkinson's disease on TOM. The relationship of TOM performance and EF in these groups was also examined. The results suggested that although TOM performance appeared compromised in the group of individuals with Parkinson's disease, the elderly control participants were relatively unimpaired relative to younger individuals. Significant relationships between several measures of TOM and EF were also found. The implications of these findings, and also the finding that failure on one measure of TOM did not necessarily predict failure on all measures of TOM, are discussed.

Aged↗
PubMed2000

Implications of test revisions for research.

Test revisions are increasingly common in psychology and neuropsychology in particular. However, such revisions may alter in complex ways the kind of information obtained, and they may assess traits, abilities, and conditions in ways different from earlier versions. This article outlines some of the problems associated with the revision of tests facing clinicians and researchers. Three broad classes of revision are considered. Part 1 considers the aging of tests, part 2 concerns the aging of participants, and part 3 considers changes in test format. Although the article focuses largely on measures of intelligence and personality, the issues addressed in the article apply to other tests and assessment domains as well.

Aging↗
PubMed2000

A study of three cases of familial related agenesis of the corpus callosum.

This paper provides data on a family in which three members, all female, have been diagnosed as having agenesis of the corpus callosum. That all three acallosal individuals came from the same family and showed relatively uniform neuropsychological impairment and could be compared in similar terms with their "callosal" siblings, also female, provides a unique sample. Inter-hemispheric transfer, psychometric measures, and motor and cognitive function were examined in the acallosal individuals, all of whom had borderline to low-average intelligence, with results compared to their non-acallosal siblings. The data indicated that all acallosal individuals exhibited deficits with the cognitive tests indicating difficulties of inter-hemispheric transfer of tactile information, difficulties in some areas of memory and, at least as far as the children are concerned, a marked difference in Verbal IQ and Performance IQ.

Adolescent↗
PubMed1999

Effect of extracellular human immunodeficiency virus type 1 glycoprotein 120 on primary human vascular endothelial cell cultures.

During the course of an HIV-1 infection, free infectious and noninfectious virus particles, and free HIV-1 proteins, circulate within the host, exposing the host endothelium to these viral factors, even if the endothelium is not infected. This suggests that extracellular HIV-1 proteins could influence endothelial cell function, leading to pathogenesis. In light of this, we have used primary cultured human vascular endothelial cells (HUVECs) to screen for effects of the HIV-1 protein gp120 on endothelial cell function. The results of this study show that short exposure of HUVEC cultures to this protein causes significant levels of cytotoxicity. Further, using several different assays, we have shown that this cytotoxic effect on HUVECs appears to be due to induction of an apoptotic program. The biphasic nature of gp120 titration curves suggests that multiple cellular factors are mediating these gp120-induced effects. Competition studies appear to confirm this by showing that the apoptotic effect is mediated through two cell surface receptors on HUVECs, CCR5 and CXCR4. Alternatively, competition studies examining CD4 receptors suggests that CD4 played no role in gp12O-induced effects on HUVECs.

Apoptosis↗
PubMed1999

Stimulation of Na+-alanine cotransport activates a voltage-dependent conductance in single proximal tubule cells isolated from frog kidney.

1. The swelling induced by Na+-alanine cotransport in proximal tubule cells of the frog kidney is followed by regulatory volume decrease (RVD). This RVD is inhibited by gadolinium (Gd3+), an inhibitor of stretch-activated channels, but is independent of extracellular Ca2+. 2. In this study, the whole cell patch clamp technique was utilized to examine the effect of Na+-alanine cotransport on two previously identified volume- and Gd3+-sensitive conductances. One conductance is voltage dependent and anion selective (GVD) whilst the other is voltage independent and cation selective (GVI). 3. Addition of 5 mM L-alanine to the bathing solution increased the whole cell conductance and gave a positive (depolarizing) shift in the reversal potential (Vrev, equivalent to the membrane potential in current-clamped cells) consistent with activation of Na+-alanine cotransport. Vrev shifted from -36 +/- 4.9 to +12.9 +/- 4.2 mV (n = 15). 4. In the presence of alanine, the total whole cell conductance had several components including the cotransporter conductance and GVD and GVI. These conductances were separated using Gd3+, which inhibits both GVD and GVI, and the time dependency of GVD. Of these two volume-sensitive conductances, L-alanine elicited a specific increase in GVD, whereas GVI was unaffected. 5. The L-alanine-induced activation of GVD was significantly reduced when cells were incubated in a hypertonic bathing solution. 6. In summary, in single proximal tubule cells isolated from frog kidney, on stimulation of Na+-alanine cotransport GVD is activated, while GVI is unaffected. Taken with other evidence, this suggests that GVD is activated by cell swelling, consequent upon alanine entry, and may play a role as an anion efflux pathway during alanine-induced volume regulation.

Alanine↗
PubMed1999

Development of the fertility adjustment scale.

OBJECTIVE: To develop a standardized measure of psychological adjustment to infertility. DESIGN: A cross-sectional two-group comparison study. SETTING: Two specialized fertility clinics in large teaching hospitals. PATIENT(S): Fifty men and 50 women undergoing evaluation and/or treatment of fertility problems. INTERVENTION(S): The Fertility Adjustment Scale was administered with the Hospital Anxiety and Depression Scale as a measure of concurrent validity. MAIN OUTCOME MEASURE(S): Scores on the Fertility Adjustment Scale and the Hospital Anxiety and Depression Scale. RESULT(S): Scores on the Fertility Adjustment Scale were distributed normally. Split-half and internal consistency were high. A significant correlation with measures of mood, anxiety, and distress provided evidence of concurrent validity. CONCLUSION(S): Preliminary results suggest that this measure will be a useful tool in assessing psychological reactions to fertility problems and outcomes of treatment.

Adaptation, Psychological↗
PubMed1999

An evaluation of a health education intervention for mid-aged women: five year follow-up of effects upon knowledge, impact of menopause and health.

An evaluation of the long term impact of a health education intervention in primary care, for premenopausal women (45 years of age), is presented. The intervention included information and group discussion about menopause, stress management, health behaviours (smoking, exercise, diet) and treatment choices. Questionnaires were sent to 86 women who had been randomised into two groups (prepared/control) and were now aged 50 (response rate 91%). The prepared group had significantly greater knowledge of menopause and attributed fewer symptoms to the menopause than the controls. There were no group differences in measures of general health or mood, but there was a tendency for the prepared group to report more interest in sexual activity. Subjective evaluation of the intervention was positive in terms of increasing knowledge and helping women to deal with the emotional and practical aspects of the menopause.

Educational Measurement↗
PubMed1999

Using intraindividual variability to detect malingering in cognitive performance.

The utility of measures for detecting malingering was evaluated using a simulation design in which half the participants were encouraged to do their best and half were asked to feign head injury. Particular attention was focused on the utility of repeated assessment (intraindividual variability) in discriminating the groups. Participants were tested on three occasions on measures commonly used to detect malingering including a specific symptom validity test (SVT). The results indicated that multiple measures of malingering obtained in single assessment (occasion one) discriminated the groups effectively. In addition, however, intraindividual variability in performance, particularly of indicators from the SVT, provided unique information beyond level of performance. The results suggest that response inconsistency across testing sessions may be a clinically useful measure for the detection of malingering.

Adult↗
PubMed1999

The Atascadero State Hospital experience. Engaging patients in violence prevention.

When it comes to caring for the forensic psychiatric inpatient, there is no "how to" book. In the forensic hospital environment, the commingling of severe and persistent mental illness with criminality poses vexing clinical challenges and complex moral dilemmas not faced in either general psychiatric or correctional environments. While providing evaluation and treatment in our maximum security forensic environment, we continually strive to create and maintain a therapeutic milieu as we fulfill our social mandate to protect the public from the dangerous "criminally insane." Few studies guide us. We do know that within the forensic population there is a spectrum of psychopathology to manage, some of which responds to traditional psychotherapeutic techniques and some of which does not. For example, patients with psychopathic traits may not respond well to traditional treatment methods (Rice, 1997). As forensic psychiatric staff, we sometimes feel as if we are making it up as we go, adapting and blending psychiatric theory with knowledge from penology and criminal justice science to provide a safe environment conducive to growth for patients, the majority of whom may be considered "violence-prone" persons (Toch, 1969). Change is a characteristic of public-sector settings (Smoyak, 1991). Forensic hospitals must continually strive to monitor, refine, and improve their organizational systems as they respond and adapt to constant change. Despite the inherent challenges posed when collaborating with forensic patients, the VAC has achieved some notable successes. Staff and patients have been encouraged to work together to create and maintain a milieu where violence is neither assumed nor condoned. An active collaboration and partnership with our forensic patients has been one component of the hospital's successful violence reduction program. We trust that ASH's successful effort to collaborate with patients on the issue of violence reduction may be of use to other forensic hospitals faced with similar challenges.

California↗
PubMed1998

Conformation and ion-channeling activity of a 27-residue peptide modeled on the single-transmembrane segment of the IsK (minK) protein.

IsK (minK) protein, in concert with another channel protein KVLQT1, mediates a distinct, slowly activating, voltage-gated potassium current across certain mammalian cell membranes. Site-directed mutational studies have led to the proposal that the single transmembrane segment of IsK participates in the pore of the potassium channel [Takumi, T. (1993) News Physiol. Sci. 8, 175-178]. We present functional and structural studies of a short peptide (K27) with primary structure NH2-1KLEALYILMVLGFFGFFTLGIMLSYI27R-COOH, corresponding to the transmembrane segment of IsK (residues 42-68). When K27 was incorporated, at low concentrations, into phosphatidylethanolamine, black-lipid membranes, single-channel activity was observed, with no strong ion selectivity. IR measurements reveal the peptide has a predominantly helical conformation in the membrane. The atomic resolution structure of the helix has been established by high-resolution 1H NMR spectroscopy studies. These studies were carried out in a solvent comprising 86% v/v 1,1,1,3,3,3-hexafluoro-isopropanol-14% v/v water, in which the IR spectrum of the peptide was found to be very similar to that observed in the bilayer. The NMR studies have established that residues 1-3 are disordered, while residues 4-27 have an alpha-helical conformation, the helix being looser near the termini and more stable in the central region of the molecule. The length (2. 6 nm) of the hydrophobic segment of the helix, residues 7-23, matches the span of the hydrocarbon chains (2.3 +/- 0.25 nm) of fully hydrated bilayers of phosphatidylcholine lipid mixture from egg yolk. The side chains on the helix surface are predominantly hydrophobic, consistent with a transmembrane location of the helix. The ion-channeling activity is believed to stem from long-lived aggregates of these helices. The aggregation is mediated by the pi-pi stacking of phenylalanine aromatic rings of adjacent helices and favorable interactions of the opposing aliphatic-like side chains, such as leucine and methionine, with the lipid chains of the bilayer. This mechanism is in keeping with site-directed mutational studies which suggest that the transmembrane segment of IsK is an integral part of the pore of the potassium channel and has a similar disposition to that in the peptide model system.

Amino Acid Sequence↗
PubMed1998

Hematuria and death secondary to aortoureteric fistula.

Ureteroarterial fistulae are extremely rare after previous vascular surgery. Eight cases have been described in the English literature. This is the first example of a vascular communication between the aorta and the ureter. All previous cases were ureteroiliac fistulae. Known hydronephrosis in the presence of prior vascular grafting and heavy hematuria should alert the clinician to the possibility of a ureteroarterial fistula.

Aged↗