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Biomedical subjects

D Sanders

Publications and source records attributed to D Sanders.

At least 181 records · Page 10Linked to original sources

Control of intracellular pH. Predominant role of oxidative metabolism, not proton transport, in the eukaryotic microorganism Neurospora.

Recessed-tip microelectrodes were used to measure internal pH (pHi) in the fungus Neurospora, and to examine the response of pHi to several kinds of stress: changes of extracellular pH (pHo), inhibition of the principal proton pump in the plasma membrane, and inhibition of respiration. Under control conditions, at pHo = 5.8, pHi in Neurospora is 7.19 +/- 0.04. Changes of pHo between 3.9 and 9.3 affect pHi linearly but with a slope of only approximately 0.1 unit pHi per unit pHo, stable pHi being reached within 3 min of changed pHo. Despite a postulated high passive permeability of the Neurospora membrane to protons (Slayman, 1970), neither active nor passive H+ transport appears critical to pHi because (alpha) specific inhibition of the proton pump by orthovanadate has little effect on pHi, and (b) cytoplasmic acidification produced by respiratory blockade is unaffected by the size or direction of proton gradient. To convert measured changes in pHi into net proton fluxes, intracellular buffering capacity (beta i) was measured by the weak acid/weak base technique. At pHi = 7.2, beta i was (-) 35 mmol H+ (liter cell water)-1 (pH unit)-1, but beta i increased substantially in both the acid and alkaline directions, which suggests that amino acid side chains are the principal source of buffer.

Butyrates↗

Indication of Gasserian ganglion coagulation for trigeminal neuralgia.

(1) Adequately extensive production of 5-gram analgesia is essential for satisfactory control of pain. (2) 87% of the 95 cases which underwent Gasserian ganglion coagulation have obtained satisfactory control of tic pain. (3) Another 6% of the cases could have satisfactory control with repeated coagulation, judged by the extent of analgesia after the first coagulation. (4) Based on the above findings we can now generally predict efficacy of this procedure.

Adult↗

Duplex Doppler scanning and spectral bruit analysis for diagnosing carotid stenosis.

Spectral phonoangiography provides accurate quantitative noninvasive assessment of carotid stenosis, but only when a carotid bruit is present. Duplex Doppler ultrasound scanning permits imaging of the carotid bifurcation and qualitative assessment of the extent of carotid stenosis. Using these two methods and commercial equipment, we compared the noninvasive results with results of carotid angiograms performed within 2 weeks of the noninvasive studies. Of 299 vessels (common, internal and external carotid) assessed by both methods in 50 unselected patients, the noninvasive combination gave results correct to within 1 mm of the angiographic value in 95% of the vessels studied. These two noninvasive methods in combination allow diagnosis and follow-up of carotid stenosis with accuracy comparable to that of angiography in patients with and without carotid bruits.

Angiography↗

Interpretation of current-voltage relationships for "active" ion transport systems: I. Steady-state reaction-kinetic analysis of class-I mechanisms.

This paper develops a simple reaction-kinetic model to describe electrogenic pumping and co- (or counter-) transport of ions. It uses the standard steady-state approach for cyclic enzyme- or carrier-mediated transport, but does not assume rate-limitation by any particular reaction step. Voltage-dependence is introduced, after the suggestion of Läuger and Stark (Biochim. Biophys. Acta 211:458-466, 1970), via a symmetric Eyring barrier, in which the charge-transit reaction constants are written as k12 = ko12 exp(zF delta psi/2RT) and k21 = ko21 exp(-zF delta psi/2RT). For interpretation of current-voltage relationships, all voltage-independent reaction steps are lumped together, so the model in its simplest form can be described as a pseudo-2-state model. It is characterized by the two voltage-dependent reaction constants, two lumped voltage-independent reaction constants (k12, k21), and two reserve factors (ri, ro) which formally take account of carrier states that are indistinguishable in the current-voltage (I-V) analysis. The model generates a wide range of I-V relationships, depending on the relative magnitudes of the four reaction constants, sufficient to describe essentially all I-V datas now available on "active" ion-transport systems. Algebraic and numerical analysis of the reserve factors, by means of expanded pseudo-3-, 4-, and 5-state models, shows them to be bounded and not large for most combinations of reaction constants in the lumped pathway. The most important exception to this rule occurs when carrier decharging immediately follows charge transit of the membrane and is very fast relative to other constituent voltage-independent reactions. Such a circumstance generates kinetic equivalence of chemical and electrical gradients, thus providing a consistent definition of ion-motive forces (e.g., proton-motive force, PMF). With appropriate restrictions, it also yields both linear and log-linear relationships between net transport velocity and either membrane potential or PMF. The model thus accommodates many known properties of proton-transport systems, particularly as observed in "chemiosmotic" or energy-coupling membranes.

Animals↗

Comparison of the accuracy of the Binkhorst, Colenbrander, and SRK implant power prediction formulas.

The prediction accuracy of the Binkhorst, Colenbrander, and SRK formulas were compared in five series from different sources totalling 654 cases. The SRK formula was superior to both the other formulas by having a smaller average error per case, a smaller range of error from highest minus to highest plus, and a smaller proportion of cases with greater than 2 diopters (D) of error in all five series studied. In four of the five series, the SRK formula also had the greatest proportion of cases with less than 1 D of error. The Colenbrander formula was superior to the Binkhorst formula in all five series with regard to average error, proportion of cases with less than 1 D of error, and proportion of cases with more than 2 D of error. The range of error from highest minus to highest plus was equivalent with the two formulas. All available published literature on the accuracy of implant power prediction formulas was reviewed and appears to support our findings.

Humans↗

Role of the plasma membrane proton pump in pH regulation in non-animal cells.

Possible methods by which eukaryotic cells can regulate intracellular pH (pHi) in response to experimental acid loading were investigated by using as a model cell the fungus Neurospora. Attention was focused on the role of membrane transport in such regulation, starting from the fact that this organism possesses a powerful electrogenic proton extrusion pump. Intracellular acidification was forced by introducing butyric acid into the recording medium, and subsequent changes in pHi and membrane potential were determined with intracellular microelectrodes. In separate experiments, membrane current-voltage curves were obtained and resolved--by an explicit kinetic model--into distinct pump and leak components. Decreased pHi causes increased outward pumping of H+ ions, in a manner quantitatively consistent with their role as a substrate for the proton pump. This increased pumping is often manifest as a transient hyperpolarization at the onset of cytoplasmic acidification. With a considerably slower time course, decreased pHi also produces a large increase in membrane leak conductance, which brings about net membrane depolarization and further stimulates the pump (by virtue of the reduced back electromotive force). Although the identity of the ion responsible for increased leak conductance is not yet known, the evident modulation of conductance seemingly plays an important role in stabilizing the intracellular pH: Stimulation of the pump alone would have little net effect on pHi because it would result simply in enhanced backflux of H+ (to which the membrane is most permeable in normal circumstances). An increased leak to nonprotons, however, would allow the pump to accomplish net H+ ejection.

Acid-Base Equilibrium↗

Physiological Control of Chloride Transport in Chara corallina: I. EFFECTS OF LOW TEMPERATURE, CELL TURGOR PRESSURE, AND ANIONS.

The rate of Cl(-) transport at the plasma membrane of the freshwater alga Chara corallina is investigated with respect to possible in vivo controls acting in addition to the two well established ones of cytoplasmic Cl(-) and cytoplasmic pH. In contrast with results from many other plant tissues, halides appear to be the only anions capable of inhibiting Cl(-) transport, either from the outside or inside surfaces of the plasma membrane. Cell turgor pressure was also investigated. It was found that neither the influx of Cl(-) nor that of K(+) or HCO(2) (-) is sensitive to turgor. Internal osmotic pressure is also insensitive to turgor, a situation contrasting with that in closely related brackish water charophytes.After temperature downshift (from 20-4 C) Cl(-) transport displays a slow, time-dependent rise. Return of cells from 4 C to 20 C results in a large stimulation of Cl(-) influx in comparison with cells maintained at 20 C throughout. This stimulation persists for several hours and is also apparent (to a reduced extent) in cells which have had cytoplasmic composition controlled by intracellular perfusion. The stimulation therefore arises, in part, from a change in plasma membrane properties. The results are discussed with respect to recent work on membrane fluidity as a function of temperature.

Journal Article↗

Physiological Control of Chloride Transport in Chara corallina: II. THE ROLE OF CHLORIDE AS A VACUOLAR OSMOTICUM.

The extent to which Cl(-) is replaceable as the major anionic constituent of the vacuole of Chara corallina was investigated. It was found that external Cl(-) is not essential in order for nongrowing cells to increase internal osmotic pressure. After growth of cells in low (9 micromolar) Cl(-), the vacuolar Cl(-) concentration is one-half that of cells grown at normal external Cl(-) concentration (850 micromolar). In contrast, both internal osmotic pressure and total concentration of the major cations, K(+) and Na(+), in the same cells were found to be only slightly sensitive to the external Cl(-) concentration. Thus, it is proposed that, at limiting external Cl(-) concentration, the cell is able to transport or synthesize another anion for vacuolar use rather than utilize a neutral solute.Although the total vacuolar (K(+) + Na(+)) concentration is relatively insensitive to low Cl(-) conditions, a large increase in K(+) was recorded. This increase in K(+) was offset by a correspondingly large fall in Na(+). This is unrelated to any mechanistic dependence of Na(+) on Cl(-) for entry into the cell but may indicate a control system acting on vacuolar sequestration of both Na(+) and Cl(-). Cells grown in low Cl(-) display an ability to take up Cl(-), at enhanced rates, from the medium. The enhancement of Cl(-) influx is maintained for several hours after external Cl(-) is raised to a high level and indicates the existence of a control on Cl(-) influx acting in addition to that of cytoplasmic Cl(-) concentration, which has a shorter decay time.The results are discussed in relation to similar work on higher plants.

Journal Article↗

Pathophysiology of "tethered cord syndrome".

The tethered cord syndrome is a clinical entity manifested by progressive motor and sensory changes in the legs, incontinence, back of leg pain, and scoliosis. In order to elucidate the pathophysiology involved in the tethered cord, the reduction/oxidation ratio (redox) was used in vivo of cytochrome alpha,alpha 3 to signal oxidative metabolic functioning in human examples of tethered cord and in animal models. Studies in experimental models indicate marked metabolic and electrophysiological susceptibility to hypoxic stress to lumbosacral cord under traction with greater weights (3, 4 or 5 gm). Similar effects were demonstrated in redox behavior of human tethered cord during surgical procedures. The authors conclude that symptoms and signs of tethered cord are concomitant with lumbosacral neuronal dysfunction which could be due to impairment of mitochondrial oxidative metabolism under constant or intermittent cord stretching. It is assumed that prolonged or accentuated neuronal dysfunction may lead to structural damage to the neuronal perikarya and later of the axons. Untethering procedures in human tethered cord improve oxidative metabolism, and probably facilitate the repair mechanism of injured neurons.

Action Potentials↗

Castleman disease: unusual manifestations of an unusual disorder.

Castleman disease was originally described in 1954 as a form of localized mediastinal lymph-node hyperplasia. It has also been reported as a solitary mass in the hilar region or peripheral lymph nodes. The authors describe 4 cases, 3 in the chest and 1 in the neck. The intrathoracic lesions involved (a) the middle portion of the superior mediastinum with extension into the neck, (b) the posterior paravertebral mediastinum with extension into the posterior intercostal spaces, and (c) the extrapleural posterior chest wall, respectively: this last case is unusual in that the tumor recurred in the same site several years after removal. The clinical, radiological, and pathological features are presented.

Adolescent↗

Dextran 40-containing incubation media: effect on lens electrolyte and water balance.

The effect of dextran 40 on lens swelling and electrolyte balance in lenses stressed by incubation in Ca++-free media was studied. Dextran 40 substantially inhibited lens swelling, Na+ gain, and K+ loss caused by six-hour incubation in Ca++-free media. After an additional 12-hour incubation in Ca++-enriched media, the water and electrolyte balance in the dextran 40-incubated group was essentially the same as that of lenses that were never exposed to a Ca++-free media. Those lenses that were not incubated in dextran 40 demonstrated significant residual lens swelling and electrolyte imbalance. It is concluded that dextran 40, by virtue of its oncotic effect, inhibits colloidal osmotic swelling and exerts a protective effect on lens function under a stress situation.

Animals↗

Bronchiolo-alveolar carcinoma: a correlative clinical and cytologic study.

From 1970 to 1977, 101 patients with bronchiolo-alveolar carcinoma were admitted to the Toronto General Hospital. Cytology preparations from 97 patients were reviewed and analyzed in correlation with biologic behavior of the tumours. The value of cytologic diagnosis was reassessed. It appears that routine cytology methods were of limited value in the investigation of patients with a peripheral solitary tumor and therefore, percutaneous fine needle aspiration with positive results in 92% of cases examined, was the only useful cytologic examination for this type of lesion. For multicentric tumors, routine cytology methods achieved positive results in 87.9% of cases and fine needle aspiration 100%. Based on cytomorphologic features, bronchioloalveolar carcinoma can be subclassified into three types: secretory, nonsecretory and poorly differentiated. In this series, 84% of solitary tumors were secretory or nonsecretory type with favorable prognosis, and 16% of solitary tumors were poorly differentiated type with poor prognosis. 55.2% of multicentric tumors were poorly differentiated type and 77.3% of multicentric tumors showed positive lymph nodes at surgery. Our results demonstrate that patients with multicentric or poorly differentiated tumors had poor prognosis.

Adenocarcinoma, Bronchiolo-Alveolar↗