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Biomedical subjects

M Hunter

Publications and source records attributed to M Hunter.

At least 73 records · Page 4Linked to original sources
PubMed1997

Interferon-gamma enhances susceptibility of cervical cancer cells to lysis by tumor-specific cytotoxic T cells.

Recently we have demonstrated that tumor-specific cytotoxic T lymphocytes (CTLs) can be activated by cervical carcinoma cells expressing the costimulatory molecule CD80, which may be used as a therapeutic vaccine for patients with cervical cancer. For activated CTLs to be effective, appropriate amounts of MHC class I expression are required on target tumor cells. In this study, we found that some cervical carcinoma cells expressed only low levels of MHC class I and adhesion molecules such as CD54. We further demonstrated that tumor cells (CaSki and SiHa) expressing low levels of MHC class I were more resistant to lysis by specific CTLs than tumor cells (HeLa) expressing high levels of MHC class I. Treatment of CaSki or SiHa cells with interferon-gamma resulted in an increased expression of MHC class I, MHC class II, and CD54. Expression of CD58 and CD80 was not up-regulated or induced. Treatment of the tumor cells with interferon-gamma significantly enhanced the lysis of the tumor cells by specific CTLs which had been activated by the respective CD80-expressing tumor cells. The enhancement of cytolysis could be blocked by monoclonal antibodies to MHC class I and CD54, but not by that to MHC class II. Furthermore, we found that interferon-gamma induced apoptosis in cervical carcinoma cells but not in tumor-specific CTLs.

B7-1 Antigen↗
PubMed1997

Cation permeation and blockade of ROMK1, a cloned renal potassium channel.

ROMK1 is an inwardly rectifying K+ channel cloned from the outer medulla of rat kidney. We have determined the permeation and blocking characteristics for several monovalent cations in ROMK1 when expressed in Xenopus oocytes, using the two-electrode voltage-clamp technique. The selectivity sequence for monovalent cations as determined by reversal potential changes under bi-ionic conditions was K+ > Rb+ > Cs+ = NH4+ >> Na+ = Li+. The conductivity for the two permeant ions K+ and Rb+ was a saturable function of the external concentration, with Km values of 11.5 +/- 1.3 mmol l-1 (n = 19) and 47.3 +/- 4.8 mmol l-1 (n = 19), respectively. With mixtures of K+ and Rb+, the conductance ratio [Rb]/[K+Rb] was varied between 0 and 1. ROMK1 was blocked by both Cs+ and Ba2+ in a concentration- and voltage-dependent manner. The electrical distance (delta) at which Ba2+ and Cs+ blocked the channel was 0.41 and 0.69, respectively, suggesting that these two ions block at different sites within the pore. Taken together with previous reports, the results indicate that ROMK1 has a multi-ion pore, and that the N-terminus contributes to the pore structure.

Animals↗
PubMed1997

Measuring health-related quality of life in rheumatoid arthritis: validity, responsiveness and reliability of EuroQol (EQ-5D).

The EuroQol (EQ-5D) generic health index comprises a five-part questionnaire and a visual analogue self-rating scale. The questionnaire may be used as a health index to calculate a 'utility' value or as a health profile. The validity, reliability and responsiveness of EQ-5D were tested in 233 patients with rheumatoid arthritis stratified by functional class. EQ-5D demonstrated moderate to high correlations with measures of impairment and high correlations with disability measures. Stepwise regression models showed that EQ-5D utility values and visual analogue scores were explained best as a function of pain, disability, disease activity and mood (R2 approximately 70%), although other variables (side-effects, years of education) were required to explain the visual analogue scores. The EQ-5D health index and visual analogue scale are more responsive than any of the other measures, except pain and doctor-assessed disease activity. The reliability of the EQ-5D index and EQ-5D visual analogue scale is as good or better than that of all other instruments except the Health Assessment Questionnaire. Some patients with severe long-standing disease had health states which attracted utility values below zero, i.e. from a societal perspective they were regarded as being in states 'worse than death'. The practical and ethical implications of these utility valuations are discussed, and at present the utility values should be used and interpreted with caution. With this caveat, EQ-5D is simple to use, valid, responsive to change and sufficiently reliable for group comparisons. It is of potential use as an outcome measure in clinical trials, audit and health economic studies, but further work is required on its performance in other clinical contexts and on the interpretation of the utility values.

Adult↗
PubMed1997

On testing the face validity of planning/problem-solving tasks in a normal population.

Clinically, tests of executive functions tend to be chosen on face validity. If such tests are to be used to evaluate a clinical population, their ability to measure executive functions should be reliably demonstrated in a normal population. In order to investigate the reliability of such tests, a sample of 130 normal adults (74 women, 56 men) ages 17 to 55 years were administered 4 tests purporting to measure planning/problem-solving: the Tower of London Test, the Six Element Test, the Twenty Questions Test, and the Rey Complex Figure Test. A structural equation modeling approach provided by the LISREL 8 program was used to evaluate three models hypothesized to explain the relationship among the test variables and the latent construct of planning/problem-solving. An adequate model was unable to be estimated, thus raising questions about the meaning of the latent construct planning/problem-solving and the psychometric structure of the Tower of London Test.

Adolescent↗
PubMed1997

Differential rates of age of seizure onset between sexes and between hemispheres?

In a descriptive analysis of 158 patients with temporal lobe epilepsy, Taylor (1969) reported that the age of first seizure varied systematically as a function of laterality and sex. We conducted inferential analyses of Taylor's original data which (1) provided support for his proposal of disproportionate left hemisphere vulnerability to seizure onset in early life, but (2) failed to provide evidence of sex differences in age of onset of unilateral seizures. Examination of these effects in a larger sample of 844 patients drawn from the Bozeman Epilepsy Consortium provided some additional support for findings from the inferential analysis. Specifically, the left hemisphere appeared more vulnerable to seizure onset in childhood, this increased vulnerability extending to about age 5 years. Age of onset of seizures was not different when males and females were compared. Thus, reanalysis of Taylor's original data as well as examination of data from a larger, more contemporary sample suggest that seizure onset varies as a function of laterality, but not sex.

Adult↗
PubMed1996

Expression of CD80 enhances immunogenicity of cervical carcinoma cells in vitro.

Although cervical carcinoma cells may express the human papillomavirus oncoproteins E6 and E7, they fail to induce an effective specific cytotoxic T lymphocyte response. This failure may be due to a lack of expression of costimulatory molecules, such as CD80 (B7.1). To augment the immunogenicity of cervical carcinoma cells, we transfected human papillomavirus (HPV)-transformed cell lines, CaSki and HeLa, with the CD80 expression vector pBJ. Alloantigens on the tumor cells were used for the stimulation of peripheral blood lymphocytes (PBLs). Cocultivation of PBLs and tumor cells resulted in proliferation of CD4+ and CD8+ T lymphocyte subsets. CD80-expressing tumor cells induced proliferation of allogeneic PBLs two-to sixfold compared to control cell lines. Cocultivation of allogeneic PBLs with CD80-positive tumor cells for 3 weeks gave rise to cytotoxic T cells capable of lysing untransfected parental tumor cell lines. Our results demonstrate an immunostimulatory effect of CD80 expression on cervical cancer cells, which provides a basis for the development of a therapeutic tumor vaccine.

B7-1 Antigen↗
PubMed1996

Role of de novo protein synthesis and calmodulin in rapid activation of Na(+)-H+ exchange of aldosterone in frog diluting segment.

1. In the amphibian early distal tubule aldosterone activates the Na(+)-H+ exchangers, resulting in an increase in intracellular pH (pHi). Since this activation is rapid (within 30 min), it may be mediated by either a genomic or non-genomic pathway. 2. pHi was measured in single microperfused early distal tubule segments using the fluorescent probe 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). 3. A 30 min incubation in aldosterone increased both resting pHi and the setpoint of the Na(+-H+ exchanger. These changes were prevented by the mineralocorticoid receptor antagonist, spironolactone. 4. Actinomycin D and cycloheximide, inhibitors of transcription and translation, respectively, were without effect on resting pHi, but inhibited activation of the Na(+)-H+ exchanger by aldosterone. 5. The effect of aldosterone upon pHi and setpoint was also prevented by the calcium-calmodulin antagonist, W-7. 6. These results indicate that, although the response to aldosterone is rapid, aldosterone binds to a specific mineralocorticoid receptor which then triggers gene activation followed by de novo protein synthesis. Furthermore, since calmodulin is a known activator of the Na(+)-H+ exchanger, and the response is inhibited by W-7, it is suggested that this protein may be calmodulin.

Aldosterone↗
PubMed1996

A prospective, randomized controlled trial of inpatient versus outpatient continence programs in the treatment of urinary incontinence in the female.

Seventy-four patients presenting with a mixed pattern of urinary symptoms were randomly allocated to undergo either inpatient or outpatient continence programs as initial treatment, without prior urodynamic investigation. Both programs consisted of physiotherapy, bladder retraining, fluid normalization, dietary advice and general support and advice. Nine out of 39 in the outpatient group and 8 out of the 35 of the inpatient group failed to complete the study. There was a significant decrease in frequency, nocturia, number of incontinent episodes and visual analog scores for both groups. In addition the outpatients had a significant reduction in loss on pad testing, and a significantly greater improvement in their visual analog score. In each group 63% were cured or improved to the extent that they did not require further treatment. Staff costs per outpatient were half those for an inpatient. We conclude that outpatient conservative treatment as detailed above is a successful first-line treatment of urinary incontinence in women. It is as successful and possibly better than inpatient treatment, and is significantly cheaper.

Adult↗
PubMed1995

Activation of a Cl- conductance by SCN- in single proximal tubule cells isolated from Rana temporaria.

1. This study investigated the effect of the anion, SCN-, on the conductive properties of single proximal tubule cells isolated from frog kidney. Ionic currents were measured using the conventional whole-cell patch clamp technique. 2. Addition of SCN- to the bath solution alone had a biphasic effect; there was an initial rapid rise, followed by a slower secondary increase, in both outward and inward conductances. However, when SCN- was added to the bath in the presence of pipette SCN-, such that the concentration gradient for movement of SCN- into the cell was abolished, only the fast changes in conductance were observed. 3. Cells did not discriminate between cations and anions under nominally K(+)-free control conditions. However, in the presence of intracellular SCN- cells became anion selective. Taken together with the increased conductance, this suggests activation of a Cl- channel (gSCN). 4. Niflumic acid, a Cl- channel blocker, inhibited gSCN in a dose-dependent manner, with a half-maximal blocking concentration (Ki) of 28 +/- 2.8 microM and a Hill coefficient of 1.2 +/- 0.3 (n = 6). 5. The activation of gSCN by intracellular SCN- was dose dependent and showed positive co-operativity, with a Ki of 62.3 microM and Hill coefficient of 4.0. 6. Plasma and urine levels of SCN- range between 10 and 70 microM, thus the conductance described here may play a role in the regulation of Cl- handling by the kidney.

Animals↗
PubMed1995

Preventing the nosocomial transmission of tuberculosis.

OBJECTIVE: To study the efficacy of expanded tuberculosis infection control measures consisting primarily of administrative controls. DESIGN: Descriptive case series. SETTING: University-affiliated, inner-city hospital. INTERVENTIONS: Introduction of expanded tuberculosis infection control measures (including an expanded respiratory isolation policy). MEASUREMENTS: The number of tuberculosis exposure episodes and skin test conversion rates of health care workers were measured before and after implementation of expanded infection control measures. Tuberculosis exposure episodes (the number of patients who were not placed in respiratory isolation at admission but who subsequently had a diagnosis of acid-fast bacilli smear-positive pulmonary tuberculosis during that admission or within 2 weeks of discharge) were compared for two time periods: the 8 months before and the 28 months after implementation of infection control measures. Tuberculin skin test conversion rates among health care workers were evaluated during a 2.5-year period. RESULTS: After expanded infection control measures were implemented, the number of tuberculosis exposure episodes decreased from 4.4 per month (35 episodes among 103 patient admissions for potentially infectious tuberculosis over 8 months) to 0.6 per month (18 episodes among 358 patient admissions for smear-positive pulmonary tuberculosis over 28 months) (odds ratio, 9.72; 95% CI, 4.99 to 19.25 [P < 0.001]). The cumulative number of days per month that potentially infectious patients with tuberculosis were not in isolation decreased from 35.4 to 3.3 (P < 0.001). A concomitant decrease in tuberculin skin test conversion rates in health care workers was seen; 6-month tuberculin skin test conversion rates decreased steadily from 3.3% (118 conversions in 3579 health care workers; 1/92 to 6/92), 1.7%, 1.4%, 0.6%, to 0.4% (23 conversions in 5153 workers [1/94 to 6/94]) (P < 0.001). CONCLUSIONS: Infection control measures effectively prevented nosocomial transmission of tuberculosis to health care workers. Administrative controls appear to be the most important component of a tuberculosis infection control program and should be the first focus of such a program, especially at public hospitals, where resources are most likely to be limited.

Adult↗
PubMed1995

Three-dimensional MRI of the glenoid labrum.

The objective of this study was to assess the accuracy of three-dimensional (3D) magnetic resonance imaging (MRI) reformation in the evaluation of tears of the glenoid labrum complex (GLC). Fifty-five shoulders were evaluated by MRI using standard spin-echo sequences. Gradient-refocused-echo axial projections were used to assess the GLC on the two-dimensional (2D) studies. Three-dimensional Fourier transform multiplanar gradient-recalled imaging with a resolution of 0.7 mm was also performed in all patients. Independent analyses of the anterior and posterior labra were performed in a blinded manner for both the 2D and 3D studies by three experienced musculoskeletal radiologists. Observations of the imaging studies were compared with the videoarthroscopic findings. The appearance of the GLC was rated on a scale of 0 to 4 (0-2 = normal, 3, 4 = abnormal or torn). The diagnostic confidence was averaged from the three reader's scores. Anterior labral tears were effectively detected with sensitivities of 89% and 96% and specificities of 96% and 100% (P < 0.0001) for the 2D and 3D studies, respectively. For posterior labral tears, the sensitivity and specificity of the 2D method were 47% and 98%, respectively. The sensitivity and specificity of the 3D volume sequence were 53% and 98%, respectively. The lower sensitivity of both imaging methods for detecting posterior labral tears may be influenced by the smaller number (n = 5) of arthroscopically confirmed cases in our study and reflects the difficulty of visualizing the posteroinferior borders of the GLC with present MRI techniques.

Adult↗
PubMed1995

Predicting cognitive impairment in epilepsy: findings from the Bozeman epilepsy consortium.

We examined the contribution of age of seizure onset, seizure duration, seizure laterality, seizure location, gender, handedness, and cerebral speech representation to cognitive attainment in 1,141 patients with medically refractory seizures. The combined influence of the predictor variables was modest. Age of seizure onset was the best single indicator of Full Scale IQ (partial r = .23) and General Memory (partial r = .20). Laterality and location of dysfunction, and cerebral speech dominance were also relevant and independent indicators of aspects of cognition. Except for age of onset of seizures (early onset was associated with poorer cognitive attainment), however, the magnitude of the effects was limited.

Adult↗
PubMed1995

Interhemispheric transfer in multiple sclerosis.

Interhemispheric transfer (IHT) was investigated in patients with multiple sclerosis (n = 20) and healthy control subjects (n = 23). On verbal dichotic listening and tachistoscopic reading tests, MS patients showed a pattern of left-sided suppression and/or right-sided enhancement, consistent with impairment of IHT. Patients with chronic-progressive MS were most affected. Clinical and empirical implications are noted.

Adult↗
PubMed1995

An audit of methotrexate and folic acid for rheumatoid arthritis. Experience from a teaching centre.

We describe an audit of 158 patients with RA treated with weekly methotrexate and 5 mg of folic acid 24 h later. Our aim was to assess the safety and efficacy of this regime in our hands compared with published clinical trials of methotrexate in RA, and to examine patient outcomes. Treatment improved ESR, but only 69% of patients continuing therapy for prolonged periods believed their arthritis to be better on treatment. Health Assessment Questionnaire and Hospital Anxiety and Depression questionnaire scores in prospectively studied patients were not significantly altered by treatment. Toxicity occurred frequently (59% in those continuing and 89% in those ceasing therapy) and cessation of therapy solely due to lack of efficacy was rare. The probability of patients continuing with methotrexate and folic acid after 1, 2, 3 and 4 yr was 87, 76, 74 and 74%, respectively, figures that are at the upper end of the reported range for methotrexate alone.

Adult↗