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Biomedical subjects

M Hunter

Publications and source records attributed to M Hunter.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1998

Measuring health status in British patients with rheumatoid arthritis: reliability, validity and responsiveness of the short form 36-item health survey (SF-36).

The objective was to assess the performance of the SF-36 health survey (SF-36) in a sample of patients with rheumatoid arthritis (RA) stratified by functional class. The eight SF-36 subscales and the two summary scales (the physical and mental component scales) were assessed for test retest reliability, construct validity and responsiveness to self-reported change in health. In 233 patients with RA, the SF-36 scales were: reliable (intra-class correlation coefficients 0.76-0.93); correlated with American College of Rheumatology (ACR) core disease activity measures [Spearman r = -0.12 (erythrocyte sedimentation rate) to -0.89 (Modified Health Assessment Questionnaire)]; and responsive to improvements in health (standardized response means 0.27-0.9). The distribution of scores on four of the eight subscales (physical function, role limitations physical, role limitations emotional and social function) was clearly non-Gaussian. Very marked floor effects were noted with the physical function scale, and both ceiling and floor effects with the other three subscales. The two SF-36 physical and mental component summary scales are reliable, valid and responsive measures of health status in patients with RA. Six of the eight subscales meet standards required for comparing groups of patients, and the physical function and general health scales may be suitable for monitoring individuals. The two scales measuring role limitations have poor measurement characteristics. The SF-36 pain and physical function scales may be suitable for use as patient self-assessed measures of pain and physical function within the ACR core disease activity set.

Activities of Daily Living↗
PubMed1998

The Northwick Park Dependency Score (NPDS): a measure of nursing dependency in rehabilitation.

BACKGROUND: Disability scores, such as the Functional Independence Measure (FIM) and Barthel Index, have been shown to correlate with care needs but cannot be used to assess them directly, as they do not indicate the number of people required to help with a task, nor the time taken. The Northwick Park Dependency Score (NPDS) is an ordinal scale that can be used to assess impact on nursing time. It takes 3-5 minutes to complete. Together with a short set of additional questions, it may be used directly to assess care needs in the community and to facilitate discharge planning. AIMS: To develop and evaluate the NPDS for use in a rehabilitation setting. METHODS: (1) DEVELOPMENT: Following a survey of existing instruments, tasks were selected on the basis of their impact on nursing time and divided into Basic Care Needs (BCN) and Special Nursing Needs (SNN). Cut-off points were devised to reflect the number of helpers needed and time taken. Following evaluation of the NPDS version 5, minor changes were made to produce version 6 which was re-evaluated on a smaller scale. (2) EVALUATION: Inter-rater and intra-rater reliability were tested in a cohort of 23 inpatients using five senior nurses. Analysis included assessment of degree of association, significant differences, absolute agreement, and agreement +1 level. Although there is no gold standard, the BCN section should correlate inversely with independently assessed Barthel scores. Re-evaluation of version 6 was undertaken using the same method of analysis in a cohort of 21 patients using three senior nurses. RESULTS: On initial evaluation inter-rater reliability testing showed an excellent level of association in total composite score between each pair of nurses (rho = 0.73-0.92, p <0.01) and agreement +1 level for individual items ranged from 73 to 100%. Significant disagreements were in six items. On re-evaluation following minor modification, high levels of association were still seen for total BCN, SNN and composite scores both between and within raters, with very satisfactory levels of agreement for individual items. The BCN section of the NPDS showed good inverse correlation with Barthel scores (rho = 0.91, p <0.01). CONCLUSION: The NPDS is simple and practical to use in a busy setting. It is shown to be reliable and valid in its assessment of nursing dependency on the ward. Its translation into a directly costable measure of continuing care needs in the community now requires evaluation.

Adolescent↗
PubMed1998

How to achieve customer service through short-cycle paperwork.

The ultimate goal of short-cycle paperwork is to satisfy customers by filling their orders as quickly as possible. Tools and techniques that can help achieve this goal include Just-in-Time paperwork elimination, process mapping, paper flow mapping, function/process mapping, work cells, and electronic kanban. Each of these is described briefly in the article.

Automation↗
PubMed1998

Validity of the Wonderlic Personnel Test as a brief measure of intelligence in individuals referred for evaluation of head injury.

Some have argued that the Wonderlic Personnel Test (WPT) may represent a brief and efficient measure of intellectual functioning (e.g., Dodrill, 1980). The present study investigated the validity of the WPT as such a measure, in individuals with head injury. The findings suggested that, although the WPT showed relatively high agreement with the Wechsler Adult Intelligence Scale-Revised (WAIS-R) in the whole group, it did not have good agreement with WAIS-R scores on an individual case basis. Since clinical practice typically seeks to evaluate individual performance, it is suggested that the WPT is not a suitable tool for psychological assessment of individuals with known or suspected head injury.

Journal Article↗
PubMed1997

Life on biomembranes viewed with the atomic force microscope.

Since its invention in 1986, the atomic force microscope (AFM) has become one of the most widely used near-field microscopes. Surfaces of hard samples are imaged almost routinely with atomic resolution. Soft biological surfaces, however, are still challenging. In this brief review, the AFM technique is introduced to the experimental biologist. We discuss recent data on imaging molecular structures of biomembranes, and give detailed information on the application of the AFM with three representative examples. One is imaging plasma membrane turnover of transformed renal epithelial cells during migration in vivo, another is visualizing a cloned and isolated potassium channel usually located in kidney, and a third is imaging macromolecular pore complexes of the nuclear envelope of aldosterone-sensitive kidney cells and of Xenopus laevis oocytes. The review ends with the conclusion that nuclear pores can serve as birthday candles on a Guglhupf.

Animals↗
PubMed1997

Two K(+)-selective conductances in single proximal tubule cells isolated from frog kidney are regulated by ATP.

1. The whole-cell and single channel patch clamp techniques were used to identify K(+)-selective conductances in single proximal tubule cells isolated from frog kidney and to examine their ATP sensitivity. Whole-cell currents were inhibited by the K+ channel inhibitors Ba2+ and quinidine in a dose-dependent manner. Addition of Ba2+ alone, quinidine alone, or both inhibitors together revealed two separate conductances, one of which was blocked by both Ba2+ and quinidine (GBa)1, the other being sensitive to quinidine alone (Gquin). 2. With Na(+)-containing Ringer solution in the bath and K(+)-containing Ringer solution in the pipette, both currents were selective for K+ over Na+. The K+ : Na+ selectivity ratio of GBa was around 50:1, while that of Gquin was 4:1. In symmetrical KCl solutions GBa showed inward rectification, while Gquin demonstrated outward rectification. 3. In the absence of pipette ATP, both GBa and Gquin ran down over 10 min. However, when 2 mM ATP was included in the pipette GBa increased, while Gquin remained unchanged. 4. Single channel studies demonstrated that a basolateral K+ channel shared several of the characteristics of GBa. It was inhibited by both Ba2+ and quinidine, underwent run-down in excised patches in the absence of ATP, and was activated by ATP. 5. We conclude that cells of the frog proximal tubule contain at least two distinct K(+)-selective conductances, both of which are regulated by ATP, and which may be involved in pump-leak coupling.

Adenosine Triphosphate↗
PubMed1997

Regulation of an outwardly rectifying Cl- conductance in single proximal tubule cells isolated from frog kidney.

1. A previous study has identified a Cl- conductance (GCl) in single proximal tubule cells isolated from frog kidney, which was activated by a protein kinase C (PKC)-dependent mechanism. 2. The whole-cell patch clamp technique was employed to examine further the properties and regulation of GCl. 3. GCl showed outward rectification, outward conductance was significantly greater than the inward conductance (56.1 +/- 15.6 vs. 16.8 +/- 6.4 microS cm-2, respectively, n = 8). DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) blocked GCl in a dose- and voltage-dependent manner. 4. Other anions permeated the conductance. The anion selectivity sequence, I- > Br- > Cl- > gluconate, followed Eisenman's sequence I. 5. GCl could be activated by ATP. This process was dependent on ATP hydrolysis and channel phosphorylation. 6. G-protein activation inhibited the ATP-dependent activation of GCl. 7. These data support the hypothesis that activation of GCl by an increase in cell volume is dependent on ATP hydrolysis and channel phosphorylation via PKC.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1997

Intracellular pH and calcium in frog early distal tubule: effects of transport inhibitors.

1. The K+ channels of the apical membrane of the diluting segment (early distal tubule, EDT) of the frog are involved in the regulation of transepithelial NaCl transport. These channels are sensitive to pHi and intracellular Ca2+ (Ca2+i). Inhibition of transport by furosemide (frusemide) results in a compensatory increase in K+ channel activity. The aims of the present study were to determine whether pHi or Ca2+i were altered by furosemide, and to identify the means by which such changes were brought about. 2. Experiments were performed using single, microperfused EDT segments. Measurements of pHi and Ca2+i were made using the intracellular fluorescent probes, 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) and fura-2, respectively. 3. Furosemide increased pHi and Ca2+i. The intracellular alkalinization was the result of an alkaline shift in the set-point of the basolateral Na(+)-H+ exchanger. This response was dependent upon the increase in Ca2+i. 4. The increase in Ca2+i produced by furosemide was due to the release of Ca2+ from intracellular stores. Depletion of these stores, by 2,5-di-t-butylhydroquinone (TBQ) and caffeine, prevented the furosemide-induced changes in Ca2+ and pH. 5. Furosemide-induced activation of Na(+)-H+ exchange was prevented by the calmodulin antagonist, W-7. 6. Thus furosemide elicits a rise in Ca2+i which, via calmodulin, results in activation of Na(+)-H+ exchange. The resulting intracellular alkalinization would be expected to increase channel activity.

Amiloride↗