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Biomedical subjects

M Hunter

Publications and source records attributed to M Hunter.

At least 19 recordsLinked to original sources
PubMed1992

The dual role of the cAMP-dependent protein kinase C alpha subunit in T-cell receptor-triggered T-lymphocytes effector functions.

In order to directly evaluate the role of the cAMP-dependent protein kinase (PKA) catalytic (C) subunit in T-cell receptor- (TCR) triggered cytotoxic T-lymphocytes (CTL) effector functions, cells were studied after pretreatment with antisense oligomers complementary to mRNA for the C alpha or C beta subunits. C alpha subunit is shown to be predominantly expressed in CTL. In some experiments the pretreatment of the CTL with the C alpha antisense, but not with the control or C beta antisense oligomers, resulted in the inhibition of cAMP-independent PKA activity without significantly affecting the level of total cAMP-inducible PKA activity. In parallel assays, CTL which were pretreated with the C alpha antisense oligomer had enhanced antigen-bearing target cell-triggered-, anti-TCR monoclonal antibody-triggered-, and phorbol 12-myristate 13-acetate/A23187-triggered exocytosis of granules, as well as enhanced antigen-specific cytotoxicity. In contrast, the TCR-triggered gamma-interferon mRNA expression and gamma-interferon secretion were inhibited in C alpha antisense-pretreated CTL. These results suggest that the C alpha subunit of PKA may have a dual role in regulation of T-lymphocytes effector functions: (i) it may down-regulate TCR-triggered protein-synthesis independent responses such as cytotoxicity and exocytosis, thereby counteracting TCR-triggered activation even in the absence of the second messenger, cAMP, and (ii) the C alpha subunit activity is likely to be required for the nuclear and/or cytoplasmic events in CTL's activation involved in lymphokine synthesis and secretion.

Animals↗
PubMed1992

Determination of fluid extraction and osmotic conductance sigma K in the lung with hypertonic NaCl infusion. I. Theory.

A dispersion and extraction model of the lung is developed to assess how the infusion of hypertonic saline into the pulmonary artery changes the gravimetric density of pulmonary venous blood. The dispersion analysis is built on the indicator dilution curve measured for the pulmonary circulation. The extraction model consists of microvascular and interstitial compartments separated by a permeable pulmonary endothelium. Because the density of fluid extracted by the hypertonic disturbance is lower than the blood density, the extraction leads to a decrease in blood density. Two cases of fluid extraction are analyzed, a hypertonic infusion to elevate the osmotic pressure in the pulmonary arterial blood in the form of a step function and an infusion performed over a period of 1 sec. Both cases show that the dispersion significantly attenuates the changes in osmotic pressure and density as they are transported by the blood along the pulmonary vasculature. Because the model has taken into account the effect of dispersion and pulmonary blood flow, the equations developed here provide the basis to calculate from the density change in pulmonary venous blood the characteristics of osmotic extraction intrinsic to the lung.

Animals↗
PubMed1992

Determination of fluid extraction and osmotic conductance sigma K in the lung with hypertonic NaCl infusion. II. Experiments.

The change in venous blood density in an in vitro rabbit lung preparation was measured after the osmolarity of the blood was elevated 17 to 50 mosmol/liter by a constant arterial infusion of hypertonic saline. We observed a transient density decrease of the blood flowing from the lung and then a return to the preinfusion density within 10 sec, an indication of the rapid completion of fluid extraction from the interstitia by the elevation in osmotic pressure. By fitting the time course of the density change with the prediction of an extraction model, we obtained the osmotic conductance sigma K (the product of the reflection and filtration coefficient) of the lung due to the increase in NaCl osmotic pressure as 1.33 +/- 0.18 ml/[hr.(mosmol/liter).g wet lung tissue] (mean +/- SEM), the interstitial volume participating in the extraction process as 0.27 +/- 0.04 ml/g of lung tissue, and the volume of fluid extracted as 1.12 +/- 0.16 microliter/g tissue for every mosmol/liter elevation. Since we also found no significant difference between the osmotic extraction parameters determined in blood-perfused lungs and those determined in plasma-perfused lungs, we concluded that the rapid density change is the result of the fluid extraction and not the flow impediment of red blood cells caused by the increase in osmolarity.

Animals↗
PubMed1992

Longitudinal Gompertzian analysis of ALS mortality in England and Wales, 1963-1989: estimates of susceptibility in the general population.

Mortality statistics in amyotrophic lateral sclerosis (ALS), which is more commonly and generally termed motoneurone disease (MND) in the United Kingdom, have been shown to reflect the incidence of previously diagnosed cases of the disease in a more complete way than in other conditions [1,2]. An analysis of changing patterns of mortality may therefore be a particularly appropriate way of tracing the underlying trends in the disease and is in principle a useful way of investigating the relationship between environmental and genetically controlled factors in the genesis of the condition. The majority of analyses so far have concentrated on the crude rise in reported mortality rates evident in recent decades in a number of countries [2-5], on the uneven geographical distribution [6,7] and on the complex range of plausible causes for these reported rises. Debates have centred on whether the increases represent 'real' or 'artifactual' changes, with no apparent resolution of the issue [8,3]. Recently Riggs [9] proposed a novel way of analysing this issue by using a Gompertzian model and provided evidence of the existence of an inherently susceptible subset of the US population. Riggs indicated that while the rise in ALS mortality is real, it is for the most part the result of an increase in the size of this inherently susceptible sub-population due to greater longevity. In order to examine the wider applicability of a Gompertzian model to ALS the technique has been replicated with the mortality rates for England and Wales for the 27-year period from 1963 to 1989. The technique has been developed and extended to produce an estimate of the size of the inherently susceptible sub-population (both male and female) over the entire period.

Adolescent↗
PubMed1992

The south-east England longitudinal study of the climacteric and postmenopause.

Fifty-six premenopausal women were drawn from a cross-sectional survey of 850 women living in South-East England. They were recontacted 3 years later when 36 met the criterion of being naturally peri- or postmenopausal. Somatic, vasomotor and emotional symptoms, as well as general health, use of medical services and beliefs about the menopause, were assessed on both occasions using the Women's Health Questionnaire (a symptom scale standardized for use with this age group). In general, the cross-sectional findings were confirmed--vasomotor symptoms, sleep problems and to a lesser extent depressed mood increased during the peri- and postmenopause. However, ratings of general health and use of medical services remained unchanged. A stepwise regression analysis was used to predict depressed mood and hot flushes in peri- and postmenopausal women. The results illustrate the importance of previously existing symptoms, stereotyped beliefs and social factors in explanations of climacteric symptoms.

Affect↗
PubMed1992

The effect of a low-fat diet on hormone levels in healthy pre- and postmenopausal women: relevance for breast cancer.

It has been postulated that differences in the levels of circulating hormones may be the explanation for the epidemiological link between per capita dietary fat intake and the incidence of breast cancer. We have investigated this possible relationship in 19 postmenopausal, and 18 premenopausal women who completed a 4-week period on a diet aiming to reduce fat intake to around 20% of total kilocalories. 7-day dietary records revealed a significant decrease in dietary fat intake in both the pre- and postmenopausal groups (from 37.2% of calories from fat to 23.2% and from 37.9 to 24.3%, respectively). There was a minor increase in the level of sex hormone-binding globulin, and a small decrease in prolactin in the postmenopausal group, which were of borderline significance. There were no significant changes in total oestradiol (E2), or non-protein-bound (free) E2 concentrations. In the premenopausal group there were no significant changes in any of the hormone levels investigated.

Adult↗
PubMed1992

Sex-related differences in the cognitive consequences of early left-hemisphere lesions.

Epileptic patients who had undergone the carotid amytal test were assessed on a variety of measures of verbal and nonverbal ability. All patients had left-hemisphere dysfunction early in life, before 1 year of age. In males, such damage results in generalized cognitive retardation regardless of the status of the cerebral speech pattern. In females, intellectual retardation is linked specifically to a shift in speech processes. This sex-related difference in behavioral outcome may reflect interruption at different maturational stages and/or the influences of the immediate hormonal milieu.

Adult↗
PubMed1992

Apical membrane potassium channels in frog diluting segment: stimulation by furosemide.

The patch-clamp technique was used to study the activity of apical membrane potassium channels in frog isolated everted diluting segments, and the effect of transport inhibitors on channel activity was assessed. In cell-attached patches with a high-potassium pipette solution and Ringer in the bath the channels show inward rectification (inward conductance, 25.1 pS; outward conductance, 10.5 pS). The channel is selective for potassium over sodium and is voltage dependent with depolarization increasing channel open probability (Po). Furosemide increased channel activity, which resulted exclusively from a significant increase in the number (N) of channels in the patch (control, 2.3 +/- 0.3, n = 8; furosemide, 4.0 +/- 0.4, n = 14) without any significant change in Po. Amiloride blocked the stimulatory effect of furosemide by reducing N to 1.4 +/- 0.6 (n = 6), and amiloride alone also reduced N with no significant change in Po. This suggests that the increase in N in response to furosemide may be secondary to a rise in intracellular pH mediated by activation of the apical Na-H exchanger.

Amiloride↗
PubMed1991

Potassium-selective channels in the basolateral membrane of single proximal tubule cells of frog kidney.

The membrane potential of proximal tubule cells is dominated by the potassium conductance of the basolateral membrane. In the present paper the nature of this conductance is investigated by the patch-clamp technique. Only one type of K channel was found in the basolateral membranes of freshly isolated proximal cells. In cell-attached patches, the current/voltage relationship is markedly non-linear with much larger inward (30 pS) than outward (approximately 6 pS) conductances, even in the presence of roughly symmetrical K concentrations. Thus the channels show inward rectification. The determination of the conductance for outward current flow is complicated since the current/voltage curves show an area of negative conductance. Nevertheless, taking the conductance for outward current flow and the density of the channels it is possible to account for all of the previously reported potassium conductance of amphibian proximal tubule cells. The open probability of the channels was found not to depend upon the membrane potential. However, the non-linearity of the current/voltage relationships will confer upon the channel the same voltage dependence as that seen in intact proximal tubules, i.e. the conductance decreases with depolarisation. Incubation of cells in Ringer with no substrates or in the presence of alanine and/or glucose showed no change in the activity of the channels. These findings suggest that, although these channels may represent the basolateral conductance of frog proximal tubule cells, they are not involved in the well-established coupling between transport rate and potassium conductance.

Animals↗
PubMed1991

Patterns of neuropsychological impairment after severe blunt head injury.

A consecutive series of 100 subjects with severe blunt head injuries was followed up 6 years after trauma. Neuropsychological test performances of 82 subjects and of a noninjured control group were analyzed by two principal components analyses (PCAs). Each PCA extracted 15 factors relating to a range of cognitive impairments, as well as neuropsychological features consistent with posttraumatic personality changes. Measures identified by the PCAs were applied to 85 head-injured subjects in the series to examine the incidence of impairment in four neuropsychological areas: disorders of learning and memory, neuropsychological features consistent with posttraumatic personality change, slowness in rate of information processing, and a range of basic neuropsychological skills. Overall, impairments occurred in 70% of the series. Disorders of learning and memory were the most common type of deficit (56.5%), with disturbances in basic neuropsychological skills the least frequent (16.5%). Variability among subjects with respect to the types and combinations of neuropsychological impairments was a characteristic feature of this clinical group, but the largest proportion (one-third) demonstrated isolated impairments. The implications of the incidence and selectivity of neuropsychological impairments are discussed.

Adolescent↗
PubMed1991

Otoacoustic emissions and auditory brainstem responses in the newborn.

The auditory function of 370 infants, drawn from both low and high risk groups, was tested before postnatal discharge using three tests: standard auditory brain stem responses (ABR), automated analysis of ABR, and automated analysis of evoked otoacoustic emissions (OAE). All infants failing any neonatal test had further audiological evaluation. Follow up information was also available on those who passed neonatal tests. Automated OAE testing of both ears was quickest (median 12.5 minutes) and least invasive (no scalp electrodes). Bilateral failure rates (and upper 95% confidence limits) with a stimulus 35-36 dB above normal hearing threshold level (nHL) were 3.0% (4.6) with automated OAE, 3.2% (5.1) with ABR, and 2.7% (4.4) with automated ABR. Automated OAE was the test most sensitive for subsequently confirmed hearing impairment. Sequential testing with automated OAE followed, in those failing this test, by automated ABR would have provided a screening test for substantial hearing impairment with a specificity greater than 99% in this population. Possible application as a universal screen is discussed.

Audiometry, Evoked Response↗
PubMed1991

'Low sodium' diuresis and ileal loss in patients with ileostomies: effect of desmopressin.

Patients with ileostomies show an early diuresis when sodium restricted; this, together with an obligatory ileal sodium loss, predisposes them to severe salt and water depletion. The role of arginine vasopressin in this circumstance and whether it is natriuretic, or antinatriuretic, is unclear. There is also controversy over its likely effect on small bowel fluid reabsorption. We have examined the effect of the non-pressor (V2) synthetic vasopressin analogue 1-deamino-8-D-arginine (desmopressin) on renal and ileal sodium and water excretion in ileostomy patients during acute adaptation to a low sodium diet. Patients were studied on two separate occasions (nonrandomised) with and without the administration of desmopressin (0.75 micrograms intramuscular, three times a day). In eight subjects without desmopressin there was pronounced diuresis on the first low sodium day, associated with a fall in renal sodium excretion and no change in ileal output or composition. In five (of the original) subjects with desmopressin there was pronounced antidiuresis, no change in renal sodium excretion, and no change in ileal output or composition. In both studies rises in plasma renin activity and salivary aldosterone concentration lagged behind the early decline in renal sodium excretion. We have confirmed the phenomenon of 'low sodium' diuresis after sodium restriction in ileostomy patients and shown that it can be prevented by desmopressin. Desmopressin has no direct or indirect effect on renal sodium excretion or ileal fluid and electrolyte loss in humans.

Aged↗
PubMed1991

Cloning and characterization of a gene encoding pig epidermal growth factor.

A portion of the pig epidermal growth factor (EGF) gene has been isolated and characterized. The nucleotide sequencies of exons 20 and 21, which encode the EGF region of the precursor protein, show 85% similarity with the human EGF gene sequence. In addition, conservation of the intron-exon boundaries between the two species was generally observed. Although the pig exon 21 appeared to lack a single nucleotide at its 5' end relative to the human gene, sequences obtained by direct amplification of the genomic DNA around the 5' end of this exon using the polymerase chain reaction, and from a pig EGF cDNA recombinant isolated from a kidney library, indicated that the deletion was probably a cloning artifact. Comparison of the predicted amino acid sequence of pig EGF with that of EGF from other species, as well as with several other polypeptides which bind to the EGF receptor, indicated conservation of Gly18, Tyr37, Gly39 and Arg41 in addition to all six cysteine residues and Leu47, which are known to be critical for biological activity. A synthetic gene encoding the predicted amino acid sequence of pig EGF was expressed in yeast. The recombinant polypeptide was shown to compete with 125I-labelled mouse EGF for binding to cells and to stimulate DNA synthesis in quiescent monolayers of Swiss 3T3 cells.

Amino Acid Sequence↗
PubMed1991

Psychiatrists injured by patient attack.

The seven staff psychiatrists injured by patient attack in a large forensic hospital in five years were compared with the 47 who were not injured by attack. Thirteen percent of the psychiatrists were injured by patient attack (2.6 percent per year); 5.5 injuries per 100 person-years occurred. This rate is comparable to the rate of injury from patient attack noted among ward nursing staff during the same period. Younger psychiatrists, and psychiatrists more recently out of residency, were more likely to be injured. Male psychiatrists were injured at a rate approximately 50 percent higher than female psychiatrists, and graduates of university-affiliated residencies were three times as likely to be injured as graduates of public-sector residencies, though these differences did not reach statistical significance. A slightly higher rate of injury was noted among graduates from non-North American medical schools. Board-certification and length of service in the hospital were not related to being injured.

Adult↗
PubMed1990

Calcium-activated potassium channels in the luminal membrane of Amphiuma diluting segment: voltage-dependent block by intracellular Na+ upon depolarisation.

Calcium-activated potassium channels in the luminal membrane of Amphiuma diluting segment were studied using the patch-clamp technique in both the cell-attached and inside-out configurations. The open probability (Po) of the channel is sensitive to both membrane potential and cytoplasmic calcium activity; depolarizing potentials and high calcium concentrations leading to an increased Po. In the cell-attached condition, channel openings were observed between pipette potentials of -100 and -240 mV. As the driving force for potassium exit from the cell into the pipette is increased the single channel currents show a biphasic response. First, the currents increase as expected; however, the single channel currents diminish in magnitude at pipette potentials more negative than -120 mV. We propose that this reduction is due to rapid blockade of the potassium channel by intracellular sodium. This proposal is supported by two facts: (a) using inside-out patches it was possible to reduce the single channel currents in a concentration- and voltage-dependent manner, similar to that observed in the cell-attached condition, by raising the sodium concentration of the fluid bathing the cytoplasmic face of the patch; (b) pretreatment of tubules with the loop-acting diuretic furosemide (10(-5) M), an agent known to decrease the intracellular sodium activity, caused an attenuation of the reduction in single channel current seen under control conditions. Given the very low Po of the channels at the resting membrane potential and the sensitivity of the channels to intracellular sodium, it is unlikely that blockade of these channels by intracellular sodium would lead to a physiological regulation of the apical K conductance.

Animals↗
PubMed1990

Stretch-activated channels in the basolateral membrane of single proximal cells of frog kidney.

Epithelial cells are capable of regulating their volume in response to osmotic swelling or shrinkage. In the present paper a channel is described which may be involved in such a volume-regulatory response. Channels were studied in cell-attached patches of the basolateral membrane of cells isolated from frog kidneys using the patch-clamp technique. The open probability of the channels is increased by the application of negative pressure to the rear of the patch pipette or by bathing the cells in hypotonic fluid. In addition, the channels are voltage-sensitive, such that depolarisation increases the open probability. The channels have a conductance of 25 pS with amphibian Ringer as the pipette solution and appear not to discriminate between potassium and sodium. Replacement of chloride by gluconate as the dominant anion in the pipette solution did not affect the current/voltage relationship, suggesting that the channels are cation-non-selective. Inward currents are observed at the resting membrane potential with either potassium or sodium as the dominant cation in the pipette solution: this obviates the channels serving a role as the route for solute exit from the cell during a volume-regulatory decrease response and suggests that they may act as the transduction mechanism sensing changes in cell volume.

Animals↗