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Biomedical subjects

M Hunter

Publications and source records attributed to M Hunter.

At least 127 records · Page 7Linked to original sources

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↗

Progressive exercise testing in closed head-injured subjects: comparison of exercise apparatus in assessment of a physical conditioning program.

Progressive exercise tests were performed on 12 closed head-injured subjects to determine 1) whether results differ when tests are performed on a treadmill, a bicycle ergometer, or mechanical stairs and 2) whether a 3-month general physical conditioning program results in an improvement in exercise performance. The subjects performed progressive exercise tests on each apparatus on entry into a residential transitional rehabilitation program and approximately 3 months later following participation in a physical conditioning program. On both the initial and 3-month exercise tests, maximal oxygen consumption (VO2 max) was significantly greater on the treadmill and the mechanical stairs than on the bicycle ergometer. The mean VO2 max was 74% of the predicted value on the initial exercise test and rose to 85% of the predicted value after the 3-month physical conditioning program. Oxygen consumption per kilogram of body weight at a given power output on a given apparatus showed no statistically significant difference between the initial and 3-month tests, indicating no change in exercise efficiency. On the 3-month test, a statistically significant decrease was noted in heart rate at rest and after the 4-minute period of recovery from maximal exercise on any given apparatus. The data obtained in this study indicate that 1) the treadmill and mechanical stairs are more suitable than the bicycle ergometer for assessing maximal exercise performance and 2) improved physical fitness following a physical conditioning program is associated with an improvement in cardiovascular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Apical potassium channels in Amphiuma diluting segment: effect of barium.

1. Single potassium channels have been studied in the apical membrane of isolated diluting segment tubules of Amphiuma using the patch clamp technique in the cell-attached mode. A kinetic analysis of the interaction of the channel with barium is presented. 2. The channel shows inward rectification, with an inward conductance of 29.2 pS and an outward conductance of 7.5 pS (cell attached, 100 mM-KCl as pipette solution). 3. The channel is mildly voltage sensitive, the open probability of 0.8 at the resting membrane potential being reduced to 0.38 mV at a hyperpolarizing potential of 120 mV. The mean open time also decreased with hyperpolarization (from 51.3 to 11.6 ms at the above potentials). 4. Inclusion of barium in the pipette solution causes a concentration- and voltage-dependent block of the channel. The open probability was reduced by 40 and 79% of control with 0.1 and 1 mM-barium respectively (0 mV pipette potential). This inhibition increases to 70 and 95% at a pipette potential of 80 mV. 5. From the voltage dependence of the blockade by barium, it is estimated that barium ions block at a site one-third of the way across the membrane. 6. Given the high open probability of the channel at resting membrane potentials and the density of the channels on the apical surface of the cells it is concluded that the channels can account for the apical potassium conductance of the diluting segment of Amphiuma.

Animals↗

Stretch-activated channels in single early distal tubule cells of the frog.

1. Single stretch-activated channels have been studied in cell-attached and excised patches from single early distal tubule (diluting segment) cells of Rana temporaria. 2. The channels can be reversibly activated, in both cell-attached and excised patches, by the application of negative pressure to the pipette causing mechanical stretching of the cell membrane. In cell-attached patches, application of 14.8 cmH2O negative pressure to the patch pipette increased reversibly the open probably from 0.11 to 0.87. 3. The channel conductance in the cell-attached configuration with standard Ringer solution in the pipette is 21.3 pS. 4. The channel is non-specific. In excised inside-out patches ion substitution experiments show that the channel does not discriminate between sodium and potassium ions, nor does it appear to select for cations over anions. 5. The channel is voltage sensitive such that depolarizing the cell opens the channel. The open probability at the resting membrane potential, 0.89, was reduced to 0.26 at a hyperpolarizing potential of 100 mV (holding pressure of -20.1 cmH2O or -206 Pa). 6. The sensitivity of the channel to mechanical stretching suggests that the channel may be involved in cell volume regulation.

Action Potentials↗

Acute changes in channel density of amphibian diluting segment.

Intracellular pH is a well-established modulator of the apical membrane potassium conductance of the amphibian diluting segment (early distal tubule). We investigated the modulation of this apical potassium conductance at the single-channel level in everted early distal tubules of the frog. Alkalinization of the bath fluid increased mean channel open probability (NPo) both in the presence and absence of the potassium-hydrogen ionophore nigericin. Reciprocal changes were seen with acidification. Because these effects were observed in cell-attached patches, where the composition of the fluid in the pipette is assumed to remain constant, the observed changes in channel activity were attributed to changes in intracellular pH. Further analysis of the data revealed that the changes in channel activity were produced exclusively by changes in the functional number of channels within the patch (N). We were unable to detect any significant changes in the single-channel open probability (Po). This suggests that the density of channels within a membrane may be far more dynamic than previously assumed.

Animals↗

Consequences and treatment of ovarian failure after total body irradiation for leukaemia.

OBJECTIVE: To assess the incidence and severity of physical and psychosexual symptoms in young women due to ovarian failure caused by total body irradiation for leukaemia and the women's response to hormone treatment. DESIGN: Postal questionnaire and interview. SETTING: Leukaemia unit of oncology hospital. PATIENTS: Consecutive series of 46 English speaking women who had developed ovarian failure after total body irradiation and bone marrow transplantation as treatment for leukaemia. RESULTS: Of the 36 responders, 33 reported some symptoms, vaginal dryness being the most common (29). This profoundly affected sexual function. Although 22 women had had sexual intercourse within six months after treatment, 16 were less interested in and 18 experienced difficulties with sexual intercourse. Anxieties about sterility, femininity, and appearance were common and reduced self confidence. Almost half reported that they had changed their social habits and restricted their social activities. Treatment seemed effective in abolishing symptoms in 24 women, but vaginal dryness remained a problem in three. Two women failed to respond and intercourse remained impossible. CONCLUSIONS: Such patients are vulnerable and access to gynaecologists and endocrinologists soon after treatment would be valuable. The optimal treatment regimen and the long term benefits of treatment have yet to be established.

Adolescent↗

Testicular seminoma. Results of the Yale University experience, 1964-1984.

Eighty-three testicular seminoma patients were treated with radiation therapy from 1964 through 1984. Seventy-nine (95%) of the 83 patients had early disease that included 61 Stage I, 15 Stage IIA (pelvic or paraaortic lymph node involvement less than or equal to 5 cm), and 3 Stage IIB (pelvic or paraaortic lymph node involvement greater than 5 cm) patients. The 15-year actuarial survival for this group of Stage I and II patients was 95% (+/- 5%). Stage I patients were treated with a mean paraaortic/pelvic dose of 2924 cGy and only one patient developed recurrent disease. This recurrence was at the margin of the radiation field and probably represents a marginal miss. The Stage IIA patients were treated with slightly higher doses (mean, 3335 cGY) to the paraaortic/pelvic region and there were no recurrences. The three Stage IIB patients received tumor doses of 3245 cGy, 4090 cGy, and 4500 cGy, respectively, and there were no recurrences. Low dose prophylactic mediastinal and supraclavicular irradiation (mean, 2320 cGy) was used in 17 (94%) of the 18 Stage II patients and there were no mediastinal or supraclavicular recurrences. Four patients presented with advanced disease (one Stage III, three Stage IV) and the only disease-free survivor was treated with cisplatinum-based combination chemotherapy and radiation therapy. Three patients developed minor complications from the radiation therapy: one patient had persistent scrotal and leg edema and two patients treated with prophylactic mediastinal irradiation had chronic low leukocyte counts. Two of the 79 Stage I and II patients developed a second malignancy: one had bronchogenic carcinoma at the margin of a mediastinal field, and one had diffuse histiocytic lymphoma both in and out of the radiation therapy fields. The 15-year actuarial probability of developing a second malignancy was 3.3%. Radiation therapy after operation is a successful treatment option for most patients with Stage I and II seminoma.

Cisplatin↗

Crystallization and preliminary X-ray studies of an aspartate aminotransferase mutant from Escherichia coli.

Mutant aspartate aminotransferase V39L (Val39 replaced by Leu) from Escherichia coli has been crystallized into a monoclinic cell from a polyethylene glycol solution (pH 7.5) by vapor diffusion. The space group and the unit cell dimensions have been determined using a precession camera, a CAD4 diffractometer and a Nicolet Xentronics area detector to be P2(1) with a = 86.8 A, b = 79.9 A, c = 89.4 A, beta = 118.74 degrees. The crystals diffract to better than 2.3 A and are suitable for X-ray structure analysis.

Aspartate Aminotransferases↗

Apical K+ channels of frog diluting segment: inhibition by acidification.

The apical potassium conductance of the amphibian diluting segment is regulated by the intracellular pH. Alkalinisation of the cytosol, whether directly by bathing the cell in an alkaline medium, or following activation of an apical Na/H exchanger by aldosterone, results in an increase in the K conductance. Early distal tubules were isolated from slices of Frog kidneys and the apical membranes exposed by everting the tubule with the aid of microperfusion pipettes. Single channels in the apical membrane were studied in the cell-attached configuration while the tubules were bathed in Ringer with a pH of either 7.4 (control) or 6.6 (acid). Under control conditions single channel currents were readily seen at the resting membrane potential. Upon acidification of the superfusion solution the open probability of the channels was decreased from 0.76 to 0.15. Thus the reduction in apical conductance is brought about, at least in part, by a reduction in the open probability of the channels upon cellular acidification.

Animals↗

Hypertension and asthma: psychological aspects.

Essential hypertensive and asthmatic patients, plus normal non-clinical controls, were compared on a number of psychological measures in order to identify the relationship between psychological distress, coping strategies and compliance behaviour. The hypothesised relationship between chronic clinical ailments and psychological distress was confirmed. The association between the presence of physical symptoms in the symptomatic condition, asthma, and greater psychological distress was also confirmed. The coping strategies adopted by the patients did not discriminate between the two clinical groups. Compliance with medication was negatively correlated with measures of psychological distress. Compliance with an appropriate healthy lifestyle was not correlated with medication compliance, although it too was negatively correlated with other measures of psychological distress.

Adaptation, Psychological↗

Staff injuries from inpatient violence.

A one-year study of staff injuries from inpatient violence at a large forensic state hospital found that 121 staff members sustained 135 injuries. Nursing staff sustained 120 of the injuries, for a rate of 16 injuries per 100 staff, and professional staff sustained three injuries, for a rate of 1.9 injuries per 100 staff. The majority of injuries to nursing staff (9.9 per 100 staff) were sustained while containing patient violence, and the rest were the result of assault (6.1 per 100 staff). Male nursing staff were nearly twice as likely as female staff to be injured and nearly three times as likely to receive containment-related injuries. The highest rates of injury were noted among ward nursing leadership. Injuries by assault were more likely than containment-related injuries to be head injuries, to cause more than three weeks' absence from work, and to affect more recently hired staff. The usefulness of the methodology in analyzing patterns of staff injury from inpatient violence is discussed.

Absenteeism↗

Cytoplasmic pH determines K+ conductance in fused renal epithelial cells.

The mineralocorticoid hormone aldosterone maintains acid-base balance and K+ homeostasis by regulating H+ and K+ secretory mechanisms in kidney epithelial cells. We have shown recently in the amphibian distal nephron that aldosterone activates a Na+/H+ exchange system in the luminal cell membrane, thus leading to transepithelial H+ secretion and cytoplasmic alkalinization. Since H+ secretory fluxes were paralleled by K+ secretion, it was postulated that the hormone-induced increase of intracellular pH activates the luminally located K+ channels. In "giant" cells fused from individual cells of the distal nephron, we measured simultaneously cytoplasmic pH and cell membrane K+ conductance during acidification of the cell cytoplasm. The experiments show that cell membrane K+ conductance is half-maximal at an intracellular pH of 7.42 and that a positive cooperative interaction exists between K+-channel proteins and H+ (Hill coefficient = 6.5). Moreover, the cellular K+ conductance is most sensitive to cytoplasmic pH in the range modified by aldosterone. This supports the hypothesis that intracellular H+ activity, regulated by the Na+/H+ exchanger, serves as the signal to couple aldosterone-induced K+ secretory flux to H+ secretion in renal tubules.

Animals↗

Respiratory effect on the blood volume of pulmonary capillaries.

We measured the density variations of aortic blood from rabbits ventilated by a positive end inspiratory pressure of 6 mmHg or a negative box pressure of the same magnitude. When calculated from the density variations, the fluctuations in blood volume of the pulmonary capillaries within one cycle as induced by an intermittent positive pressure ventilation were found to be similar to the ones induced by an intermittent negative pressure ventilation. Using these volumetric fluctuations as a means to assess the transpulmonary pressure and the transmural pressure across the pulmonary capillaries, we conclude that the switching of the ventilation method did not alter the cyclic fluctuations of these pressures.

Animals↗

Whole-cell potassium currents in single early distal tubule cells.

The apical membrane potassium conductance of amphibian early distal tubules is sensitive to changes in the intracellular pH, with cellular acidification causing a decreased conductance. With the whole-cell patch-clamp technique, we have measured the total potassium conductance of single isolated early distal tubule cells of the frog. With symmetrical potassium gluconate solutions, the whole-cell current was found to be strongly rectifying, with an inward conductance of 12.9 nS (at intracellular pH between 7.6 and 8.0) and an outward conductance of 1.0 nS. The inward current was almost totally inhibited by the addition of 10 mM Ba2+ to the bath solution. The use of pipette solutions with pH between 7.0 and 8.0 showed a positive correlation between intracellular pH and conductance. In contrast, acidification of the extracellular solution caused no significant change in conductance.

Animals↗