Activation of the electrogenic sodium pump in guinea-pig atria by external potassium ions. 1. When cardiac preparations are rewarmed following prolonged hypothermia a transient hyperpolarization occurs in K-containing media. This hyperpolarization is correlated with the active Na efflux. It might be due to electrogenic Na pumping or to extracellular K depletion brought about by the activity of an electroneutral Na-K exchange pump. In order to distinguish between these mechanisms the effect of various extracellular K concentrations ([K](o)) on the membrane potential of guineapig atria was studied before and after hypothermia.2. The membrane potential increased with decreasing [K](o) before cooling. It reached values of -64 and -92 mV at 10.8 and 0 mM-K, respectively.3. The membrane hyperpolarized transiently after hypothermia beyong the potential observed before cooling. Maximal values of about -94 mV were obtained during rewarming in solutions containing 0.4-2.7 mM-K. The membrane potential was significantly lower (-88 mV) in K-free media. It was also diminished at [K](o) higher than 2.7 mM and was measured to be -74 mV at 10.8 mM-K.4. The hyperpolarization of the cell membrane during the first 20 min of rewarming was maximal at 2.7 mM-K and yielded 15.5 mV. The hyperpolarization amounted to 7.2 and 10 mV at 0.4 and 10.8 mM-K, respectively. No hyperpolarization occurred in K-free solutions.5. The rate of decline of the transient hyperpolarization increased with [K](o).6. Variations of membrane input resistance after changes in [K](o) were measured in rewarmed atrial trabecula. The measurements revealed an increase in membrane resistance in lower [K](o).7. It is concluded that the transient hyperpolarization of the cardiac cell membrane during rewarming is due to the activation of an electrogenic Na pump.8. The (relative) strength of the pump current at various [K](o) was derived from the observed dependence of the hyperpolarization and of the membrane input resistance on [K](o). The current is estimated to be half-maximal at about 1.5 mM-K.


Properties of twitch motor units in snake costocutaneous muscle. 1. Single motor units of twitch muscle fibres were studied in isolated nerve-muscle preparations of m. costocutanei inferiores from grass and garter snakes. Preparations were superfused with Ringer solution at a controlled temperature of 22 degrees C.2. The peak and time-to-peak tension (contraction time) were measured for isometric twitches of forty-seven whole muscles and 83 motor units. The sample of motor units was drawn from an estimated total population of 213-355 twitch units. Peak tetanic tensions were also measured. The measurements were made at muscle lengths at which the twitch tension was maximal, and this length was not always the same for whole muscle and unit twitches. In fifty-nine cases 1 and in twelve cases 2 motor units were isolated from each muscle.3. Whole muscle contraction times ranged from 22-61 msec (mean +/- S.D. = 40.3 +/- 9.8 msec) and those for units from 18-92 msec (mean +/- S.D. = 46.9 +/- 15.9 msec). The wide range for whole muscles is discussed.4. The percentage of the whole muscle tetanic tension contributed by each unit (unit size) was calculated. Contraction time was inversely related to unit size.5. Twitch-tetanus ratios were calculated and found not to be related to unit contraction time.6. The conduction velocities of axons innervating 23 motor units were calculated from latency measurements at two points along the length of the nerve. They ranged from 1.9 to 10.4 m/sec. Axon conduction velocity was inversely related to unit contraction time, and directly related to unit size.


Post-tetanic potentiation of twitch motor units in snake costocutaneous muscle. 1. Isometric twitch responses of single motor units in snake costocutaneous muscle have been recorded before and after conditioning tetanic stimulation. 2. Most units showed post-tetanic potentiation of twitch tension, associated with increased maximal rate of rise of twitch tension, and in some cases also associated with prolongation of twitch contraction time. A few units showed a short phase of actual depression of the post-tetanic twich responses, followed by potentiation. 3. The time course and magnitude of post-tetanic changes of twitch tension and maximal rate of rise of tension could be described by the sum of three processes which are assumed to be maximal close to the end of the conditioning tetanus: (i) a rapidly declining potentiation (called here early potentiation, which lasted less than 2 sec) which may have a purely mechanical origin; (ii) a much slower-declining potentiation (called here prolonged potentiation, which lasted up to 15 min); and (iii) a process which lasted up to 60 sec during which twitch potentiation was reduced. The latter process (called here depressed potentiation) was usually apparent as a marked trough in the plots of twitch amplitude versus time after the conditioning tetanus, and occassionally was evident as an actual transient depression of twitch amplitude after the tetanus compared with that before. 4. The effects of the prolonged potentiation and the depressed potentiation on the maximal effect of each process close to the end of the tetanus were extracted by fitting single exponential equations to different portions of the data, using a computer program. 5. Twitch potentiation associated with increased maximal rate of rise of tension seemed to be a separate phenomenon to that associated with prolongation of contraction time, seen when conditioning tetani of higher frequency and numbers of stimuli were employed. The depressed potentiation of twitch tension tended to be partly masked in cases where contraction time was prolonged, but this did not affect the depressed potentiation of maximal rate of rise of tension. 6. The post-tetanic potentiation shown by a unit was related to the contraction time of the unit, in addition to the well known relationship to the initial twitch-tetanus ratio. The depressed potentiation may correlat more closely with the initial twitch-tetanus ratio than with the unit contraction time. 7. The magnitude of maximal depressed potentiation shown by a unit may be directly correlated to that of maximal prolonged potentiation. 8. The time constant of decay for prolonged potentiation of twitch tension tended to be related inversely to unit contraction time and directly to unit size and the maximal value of prolonged potentiation oftwitch tension. The time constant of decay for prolonged potentiation of maximal rate of rise of tension tended to be related to unit size and initial twitch-tetanus ratio, and the time constant of decay for depressed potentiation of rate of rise of tension tended to be related to unit size. 9...


The dependence of membrane potential on extracellular chloride concentration in mammalian skeletal muscle fibres. 1. The steady-state intracellular membrane potential of fibres in thin bundles dissected from mouse extensor digitorum longus or soleus muscles or rat sternomastoid muscles was measured with 3 M-KCl glass micro-electrodes. The steady-state membrane potential was found to depend on the extracellular concentrations of Na, K and Cl ions. 2. The resting membrane potential (3.5 mM-[K]o, 160 mM-[Cl]o) was -74 +/- 1 mV (mean +/- S.E.) and a reduction in [Cl]o to 3.5 mM caused a reversible steady-state hyperpolarization to -94 +/- 1 mV (mean +/- S.E.). 3. The steady-state membrane potentials recorded in fibres exposed to different [K]o and zero [Cl]o were consistent with potentials predicted by the Goldman, Hodgkin & Katz (GHK) equation for Na and K. The results of similar experiments done with Cl as the major external anion could not be fitted by the same equation. 4. The GHK equation for Na, K and Cl did fit data obtained from fibres in solutions containing different [K]o with Cl as the major external anion if the intracellular Cl concentration was allowed to be out of equilibrium with the steady-state membrane potential. 5. It is suggested that an active influx of Cl ions controls the intracellular Cl concentrations in these fibres and hence maintains the Cl equilibrium potential at a depolarized value with respect to the resting membrane potential. 6. The steady-state membrane potential of rat diaphragm fibres was independent of [Cl]o and it seems likely that the intracellular Cl concentration of these fibres is not controlled by active Cl transport.


The permeability of the secretin stimulated exocrine pancreas to non-electrolytes. 1. A method of measuring the permeability of the pancreas by determining the apparent reflexion coefficient (sigmaA) is described, in the isolated pancreas secreting maximally under the influence of secretin. The principle is to add a non-electrolyte to the perfusate which will create an osmotic gradient (RTsigmadeltaC) counter to that of active transport and reduce the secretion rate. This is compared with the effect of an equal concentration (0.1 M) of sucrose (RTdeltaC; sigma = 1). The apparent reflection coefficient is obtained by dividing the percentage reduction in the secretion rate due to the test molecule with that due to sucrose. 2. Sucrose when added to the perfusate inhibits pancreatic secretion. For every 10 mM increase in sucrose concentration, the secretion rate was inhibited by 7.1%. It has been estimated that an osmotic gradient of 131 m-osmole/kg water will cause zero flow rate. This is a measure of the pressure required to counteract the local osmotic gradient set up by active transport, it is equivalent to about 3.4 atm. 3. Non-electrolytes with molecular volumes greater than about 85 cm3 mole-1 are relatively impermeable, below this value they enter the pancreatic juice with increasing ease as the molecular volume decreases. 4. SigmaA for a number of compounds has been measured: urea 0.17; ethanediol 0.27; thiourea 0.51; glycerol 0.69; creatinine 0.81; erythritol 0.91; arabinose 0.96; xylose 0.98; sorbitol 0.98. 5. The addition of non-electrolytes to the perfusate had effects on pancreatic secretion which were a function of sigmaA. For molecules with sigmaA lying between 0.81 and 1.0 an osmotic load of 0.1 M increased both the concentration of sodium plus potassium and the concentration of chloride plus bicarbonate by about 50 m-mole/l. Whereas the cation change is almost exclusively one of sodium that of the anions was preferentially an increase in chloride. For compounds with sigmaA lying between 0 and 0.81 the concentration of sodium plus potassium was proportional to sigmaA. 6. A number of compounds have been described which inhibit pancreatic secretion, other than by an osmotic effect. These include acetaldehyde, thioglycerol, nicotinamide, ribose, dihydroxyacetone, and glyceraldehyde. 7. It is concluded that the pancreas is more permeable than the gall-bladder of rabbit, fish and bullfrog, the proximal tubule of the kidney of rat and the small intestine of bullfrog, but is probably similar to that of small intestine of guinea-pig and man.


Renal handling of phenol red. III. Bidirectional transport. 1. The renal excretion of phenol red and other phenolsulphophthalein dyes (bromophenol blue and bromothymol blue) was studied in clearance experiments on anaesthetized rabbits. 2. Net tubular excretion of phenol red reached a maximal value of 8 mumole/min at a plasma concentration of ultrafiltrable dye of about 0.1 mM and was decreased at higher plasma concentrations. Decreases in net tubular excretion at high plasma concentrations were also obtained for bromophenol blue and bromothymol blue suggesting tubular reabsorption in addition to tubular secretion of the dye. Conclusive evidence for reabsorption was provided by administration of probenecid which caused a fall in the excretion of the dyes below that filtered by the glomeruli. 3. Tubular reabsorption of phenol red during probenecid administration appeared to be proportional to the glomerular load and was increased under experimental conditions leading to a decrease of urinary pH. Experiments involving efflux of phenol red from liposomes gave no evidence of a significant role of transmembrane passage by non-ionic diffusion. It is suggested that the pH dependence of the reabsorptive process is the result of preferential reabsorption of the acid as compared to the basic form of the indicator dye across a hydrophilic pathway in the transporting membranes. 4. Clearance ratio of phenol red to that of p-aminohippurate at low plasma concentrations was about 0.3. They low degree of extraction of phenol red from renal plasma is attributed both to tubular reabsorption and binding of the dye by plasma proteins.


Axonal conduction velocity and voluntary discharge properties of individual short toe extensor motor units in man. 1. The axonal conduction velocity and the voluntary discharge properties of 120 short toe extensor motor units were studied in man. 2. Electromyographic techniques were used which permitted the identification of individual motor unit potentials after proximal and distal electrical nerve stimulation and during maximum voluntary effort. 3. The necessary selectivity of the e.m.g. recordings was achieved in two circumstances. In some subjects, previous motor nerve lesions distal to the point of stimulation had led to collateral sprouting with larger motor unit potentials. In other subjects an accessory deep peroneal nerve was present, so that lidocaine block of the main motor nerve left a small number of innervated motor units. 4. The axonal conduction velocities of the individual motor units ranged from 30 to 54 m/sec with most motor units between 35 and 45 m/sec. 5. Motor units which voluntarily could be driven continuously at frequencies below 10/sec had axonal conduction velocities between 30 and 45 m/sec. 6. Motor units which on voluntary drive responded only in high frequency bursts had axonal conduction velocities between 40 and 54 m/sec. 7. Motor units with intermediate voluntary discharge properties had intermediate axonal conduction velocities. 8. Thus a relationship was established between voluntary discharge properties and axonal conduction velocity.


Morphology and organization of axon collaterals from afferent fibres of slowly adapting type I units in cat spinal cord. 1. The morphology of the collaterals of single axons innervating Type I slowly adapting receptors was studied by using the intra-axonal injection of the enzyme horseradish peroxidase in anaesthetized cats. The axons were impaled near their dorsal root entrance zone in the lumbosacral cord. The morphology was revealed by subsequent histochemistry. 2. Thirteen Type I axons were stained, nine with receptors in the hairy skin and four with receptors in the glabrous foot pad skin. Twelve axons could be traced back into their dorsal roots and 11 of these divided into rostral and caudal branches shortly after entering the spinal cord. 3. One hundred and twelve collaterals were given off the thirteen axons and all well filled collaterals had a similar morphology. In the dorsal horn they gave rise to wide elliptical areas of terminal arborization (in transverse sections of cord) that were limited to laminae III, IV and the dorsal part of lamina V. The terminal arborizations of collaterals from the same axon were in line in the saggittal plane, but only rarely did the terminal arborizations of adjacent collaterals overlap; usually there was a gap between adjacent terminal arborizations. 4. Synaptic boutons of Type I units from hairy skin were mainly of the "en passant" variety whereas those of Type I units from glabrous skin were generally "boutons terminaux" with very few boutons "de passage". 5. The morphology of axon collaterals of Type I units is compared with that of hair follicle units.


The effect of acute and chronic hypoxia on thoracic gas volume in anaesthetized rats. 1. Thoracic gas volume at end expiration (functional residual capacity, FRC) was measured in chronically and acutely hypoxic anaesthetized rats by a plethysmograph method. 2. FRC, measured during air breathing, was 34-62% larger in rats which had been kept in an environmental chamber in 8, 10 or 12% O2 for 3 weeks than in littermate controls. FRC returned to normal after the rats had returned to air for 9 days. There was no constant difference in the pattern of breathing between control and chronically hypoxic rats. 3. Pressure-volume curves measured post mortem showed no difference in the volume of the lung at 25 cm H2O pressure or in the compliance of the lung between chronically hypoxic and control rats. Thus there was no gross mechanical change in the lung to account for the increase in FRC. 4. Acute hypoxia caused by breathing 12% O2 increased FRC in control but not in chronically hypoxic rats. The increase in FRC in control rats was abolished by combined blockade of the vagus nerves and carotid bodies (with procaine) but not by vagal blockade alone. 5. The combined vagal and carotid body blockade reduced FRC significantly in rats which had been in 10% O2 for 3 days but not in those which had been in 10% O2 for 21 days. 6. Lung area measured from radiographs was not reduced by a muscle relaxant in chronically hypoxic rats. Electromyograms from anterior intercostal muscles and the diaphragm showed no electrical activity in expiration in chronically hypoxic rats which might indicate an active muscular basis for their increased FRC. However when FRC was raised by acute hypoxia in control animals there was also no increase in electrical activity in expiration which could have explained their increase in lung volume. 7. We concluded that the increase in FRC during acute hypoxia in control rats was probably due to a reflex from the carotid body. The increase in FRC in chronically hypoxic rats, which was present while they breathed air, may have had an active muscular component in the early stages but later on there was possibly a structural factor in the chest wall.


The representation of facial temperature in the caudal trigeminal nucleus of the cat. 1. In cats anaesthetized with urethane, extracellular micro-electrode recordings were made in the marginal layer of the trigeminal nucleus caudalis between the level of the obex and the Cl rootlets. 2. Nearly 300 neurones were found whose discharge rate increased with a reduction of facial temperature and a few which were excited by an increase in temperature. Over half of the neurons in each group were specifically sensitive to temperature and the remainder had a weak input from mechanical stimulation of the face. 3. Thermal receptive fields were all ipsilateral and found most frequently on the nose, lips, lower eyelid and pinna. There was a somatotopic organization of the receptive fields according to the three divisions of the trigeminal nerve. 4. On quantitative thermal testing, the neurones showed responses which were similar to those of the skin temperature sensors. 5. The thermal neurones could be antidromically fired by a stimulating electrode in the thalamus.


Nucleoside transport in sheep erythrocytes: genetically controlled transport variation and its influence on erythrocyte ATP concentrations. 1. The permeability of sheep erythrocytes to purine and pyrimidine nucleosides was investigated. Erythrocytes from most sheep (nucleoside-impermeable) were almost completely impermeable to 5 mM inosine whereas cells from approximately 5% of the animals studied (nucleoside-permeable) showed a rapid inosine uptake. Cells from both types of animal were permeable to 5 mM adenosine, although transport was slower in nucleoside-impermeable erythrocytes. 2. Two distinct nucleoside transport routes were present in nucleoside-permeable erythrocytes; a high affinity (apparent Km congruent to 0.2 mM) facilitated diffusion system which transported both purine and pyrimidine nucleosides, and a non-saturable uptake route selective for adenosine. The high affinity system was the major route of adenosine transport at physiological concentrations. 3. Transport by the high affinity system was completely inhibited by micromolar concentrations of dipyridamole and nitrobenzylthioinosine. Dipyridamole had no effect on the non-saturable component of adenosine uptake. 4. The transport differences between nucleoside-permeable and impermeable erythrocytes were due to the absence of the high affinity system from nucleoside-impermeable cells. 5. Nucleoside-permeable cells had a higher intracellular ATP concentration than nucleoside-impermeable erythrocytes, suggesting that the high affinity transport system participates in the energy metabolism of the cell.


Plasma vasopressin levels during hypoxaemia and the cardiovascular effects of exogenous vasopressin in foetal and adult sheep. 1. Fotetal plasma vasopressin levels were measured by bio-assay in chronically catheterized sheep from 110 to 145 days gestation. 2. In foetuses in good condition resting circulating vasopressin concentrations were generally undetectable (less than 5 micromicron./ml.). In 15% of the samples low concentrations (5-10 micromicron./ml.) were observed. 3. Hypoxaemia in the foetus was caused by allowing the ewe to breathe 9% O2-3% CO2 in N2 for 1 hr. Plasma vasopressin levels rose in the foetus to 119 +/- 32 micromicron./ml., whereas the hormone levels in the ewe were not routinely increased. In the foetus, the rise in plasma vasopressin levels was significantly related to the fall in pH and Pa, O2 during the hypoxia. 4. In foetuses in which the cervical vagosympathetic trunks were cut, the rise in plasma vasopressin levels (to 48 +/- 25 micromicron./ml.) during hypoxaemia was less than in intact foetuses. The increase was related only to the fall in arterial pH and the regression coefficient was less than in intact foetuses. 5. During hypoxaemia arterial pressure rose and heart rate fell in the normal foetuses. The rise in arterial pressure was greatest when the plasma vasopressin concentration was highest. 6. Spontaneous episodes of hypoxaemia (Pa, O2 less than 15 mmHg) and/or acidaemia (pH less than 7.30) occurred in four intact foetuses and four foetuses in which the cervical vagosympathetic trunks were cut; all of the latter lambs died in utero. Plasma vasopressin levels were elevated and the concentrations were inversely related to arterial pH. 7. Intravenous infusions of vasopressin to foetuses increased plasma vasopressin levels to 6-202 micromicron./ml.; the rate of clearance of the hormone was three times that in adult ewes. There was a large increase in arterial pressure and bradycardia. The hypertensive effects of vasopressin were relatively much greater in the foetus than in adult ewes.


Blood flow in the resting forearm during prolonged contralateral isometric handgrip at maximal effort. 1. In earlier studies we have shown that muscle contraction performed as handgrip at constant force, one third of maximal voluntary contraction (MVC), induces a rapid vasodilation in the resting contralateral forearm which in all probability is neurogenically mediated, followed by a relative increase in resistance.2. The maintenance of contraction at one third MVC for 2 min requires continuously increasing effort because of fatigue, as also evidence by the e.m.g. The biphasic response of the vascular bed may then be related to the increasing intensity of somatomotor activation which is needed to maintain contraction force, or, alternatively, to differences in vasomotor activity on initiation of and continued muscle activity.3. To elucidate these two possibilities blood flow in the resting forearm was measured during contralateral handgrips at constant maximal effort for 6 min (in which case force will drop) and compared to handgrip at constant force, one third MVC, for 2 min.4. The flow reaction during prolonged contraction at maximal effort was similar to that induced by contraction at constant force with a marked transient lowering of vascular resistance, although maximal vasodilation tended to be more pronounced and occur earlier.5. The results indicate that the rapid decrease in vascular resistance is related primarily to the initiation of somatomotor activity, whereas continued muscle contraction produces a relative increase in vasoconstrictor activity irrespective of changes in contraction effort.


A study of the composition of pericardial fluid, with special reference to the probable mechanism of fluid formation. The composition of pericardial fluid and simultaneously withdrawn plasma have been measured in rabbits and greyhounds. 1. Sodium and chloride distributions were found to be not markedly different from the ratio predicted for a passive distribution. The small deviation found in greyhounds could be largely corrected by the in vitro dialysis of plasma against pericardial fluid. 2. Calcium and magnesium were distributed in a manner expected from a passive ultrafiltrate of plasma. 3. Pericardial fluid was found to contain between one quarter and one third of the protein of plasma. 4. Separation of the protein constituents demonstrated a far higher proportion of albumin to other proteins in the pericardial fluid. 5. The osmolality of plasma was slightly higher than that of pericardial fluid, as would be expected from a plasma ultrafiltrate. 6. The potassium concentration of pericardial fluid was higher than the plasma concentration in all animals studied. This difference could be abolished, and an expected distribution obtained in the samples from greyhounds, by the in vitro dialysis of plasma against pericardial fluid. This observation for potassium cannot be attributed to haemolysis of blood in pericardial fluid samples or to the use of any inappropriate references. It is suggested that the elevated potassium concentration of pericardial fluid may reflect the lability of the cardiac intracellular potassium during cardiac contraction. 7. The results obtained in this study do not support the concept of an active secretion of pericardial fluid as has been claimed by others. The distribution of ions would appear to be passive and to follow the values predicted by the Gibbs-Donnan relationship.


Discrimination between descriptive models of L-glutamate uptake by the retina using non-linear regression analysis. 1. The uptake of labelled L-glutamate by the isolated rat retina was measured over a large range of external concentrations (1 micron to 1 mM). 2. The results obtained from measurements of the initial velocity of L-glutamate uptake at different concentrations did not follow simple hyperbolic kinetics. 3. The error structure of replicate velocity measurements was examined and found to be normally distributed and heteroscedastic. 4. Descriptive models were fitted directly to data, weighted by the invariance, using non-linear regression analysis. 5. The most suitable suitable descriptive model consisted of a saturable hyperbola (Vm = 285 n-mole.(g wet wt.)-1.min-1, Km = 252 micron) and a linear term (b = 0.45 min-1).


Mechanisms of functional recovery and regeneration after spinal cord transection in larval sea lamprey. 1. Large sea lamprey larvae, close to metamorphosis, regained swimming coordination after several weeks following complete spinal cord transection. Recovery was much faster when animals were kept at 23 than at 12 degrees C. 2. The behavioural recovery involved a regenerative mechanism in the spinal cord, since stimulation of the head resulted in tail curling, even when all tissue other than spinal cord and notocord was stripped away for several cm above and below the transection. 3. Following complete behavioural recovery, stimulation of the rostral cord evoked electrical signals recorded from the cord dorsum for only 10 mm below the transection. 4. Dorsal cells and giant interneurones, which normally project to the brain, could not be antidromically activated across the transection zone. However, giant interneurones could be activated polysynaptically by descending volleys. 5. Twelve of eighteen large reticulospinal axons followed in serial sections regenerated across the glial-ependymal scar, but branched abnormally and migrated away from their customary locations. They became smaller, and were finally lost within 4 mm of the centre of the transection zone. 6. These data suggest that behavioural recovery does not involve long axon tract regeneration. An alternate hypothesis, that short distance sprouting of axons across the transection zone may result in synapse formation with propriospinal interneurones which relay the necessary information, is discussed.


Changes in the intracellular sodium activity of sheep heart Purkinje fibres produced by calcium and other divalent cations. 1. The intracellular Na activity of sheep heart Purkinje fibres was recorded with Na+-sensitive glass micro-electrodes. The effects of various external divalent cations on the intracellular Na activity were investigated. 2. Raising the external concentration of divalent cations (Ca, Mg, Mn, Sr or Ba) from 3 to 16 mM resulted in a decrease in the intracellular Na activity of 10-50%. 3. Raising the external concentration of Ca, Sr or Ba could produce a decrease in the intracellular Na activity even when the Na-K pump was inhibited (with strophanthidin, 10(-5) M); but raising the external concentration of Mg or Mn could not. 4. Mn inhibited the decrease in the intracellular Na activity produced by raising external Ca while the Na-K pump was inhibited. 5. Raising external Ca or adding Mn reduced the rate of rise of the intracellular Na activity on inhibition of the Na-K pump. 6. The removal of external K resulted in an increase in the intracellular Na activity. This increase could be stopped and even reversed by raising external Ca. 7. Removal of divalent cations from the external solution produced an increase in the intracellular Na activity. However, replacing external Ca and Mg by another divalent cation, e.g. Mn, did not result in a rise in the intracellular Na activity, except when the Na-K pump was inhibited. 8. The intracellular Na activity decreased by approximately 50% for a tenfold increase in the external Ca concentration. 9. The extent of the decrease in internal Na activity produced by raising external Ca was directly proportional to the internal Na activity before external Ca was raised. 10. We conclude that external Ca influences the intracellular Na activity in two ways: (a) by changing the passive Na influx: the resultant change in the intracellular Na depends on the activity of the Na-K pump; and (b) by a process where internal Na ions are exchanged for external Ca ions.


Selective impairment of contrast sensitivity in kittens exposed to periodic gratings. 1. Kittens were exposed to a periodic grating orientated vertically during the critical period of their life. 2. At the end of the critical period the amplitude of the response to drifting gratings was found to be reduced at the spatial frequency of exposure in multi-unit and in some single unit recordings at lateral geniculate level. 3. The contrast sensitivity measured with behavioural methods also showed a depression at the spatial frequency of exposure. 4. An analysis of the preferred stimulus orientation of cortical units in area 17 showed that all orientations were represented.


The influence of stimulus velocity on the responses of single neurones in the striate cortex. 1. Using a multi-histogram technique forty-seven response-velocity curves were prepared for a variety of visual stimuli presented to twenty-one cells in the striate cortex of the anaesthetized, paralysed cat. 2. The character of each velocity-response curve varied according to the measurement used in assessing a response. Reasons are advanced for sampling the response over a single bin of short duration at the peak of the discharge in each average response histogram. 3. The sharpness of tuning varied markedly throughout the population of cells but it was not possible to establish any definitive class differences. 4. For simple and complex cell categories there was considerable overlap in both the range of effective stimulus velocities and the distribution of the optimal velocities. An observation not emphasized in the past was that some simple cells responded to very fast stimuli while a number of complex cells were driven by very slowly moving stimuli. 5. Generally changes in stimulus parameters such as the polarity of contrast of a moving edge, its orientation or direction of movement produced only slight modifications in the profile of the velocity-response curve. 6. The abolition of the response of simple cells that failed to be driven by rapidly moving stimuli was shown to be due to the entry of the stimulus into the inhibitory flank distal to the discharge region. When the movement of the stimulus was confined to the discharge region there was little evidence of velocity dependence in the response. The duration over which the inhibition from the distal flank remained effective was evaluated for representative simple cells.


Thermal stimulation of intra-abdominal veins in conscious rabbits. 1. Infusions of hot and cold Hartmann's solution were given into the hepatic portal vein and inferior vena cava of conscious rabbits. Similar infusions were given into an ear vein as controls. The time integral of the displacement of brain temperature was measured. 2. There was no evidence for the presence of warm sensors in the inferior vena cava, portal vein, liver or hepatic vein, and no evidence for a concentration of cold sensors in the inferior vena cava. 3. There may be cold-sensitive elements in the portal vein or the tissue perfused by blood passing through it.


Accumulation of amines by rabbit erythrocytes in vitro. 1. Accumulation of noradrenaline (NA), 5-hydroxytryptamine (5HT) and tyramine by rabbit erythrocytes was measured at 37 degrees C in vitro. 2. Of the amines used only NA was broken down during incubation. This was a result of intracellular catechol-O-methyl transferase activity. 3. NA and 5HT entered the red cells by similar processes which were temperature-sensitive (cooling to 0 degrees C inhibited accumulation) and had saturation kinetics. The entry of NA was partially stereospecific; the (-)-isomer accumulated twice as fast as did (+)-NA. 5HT and NA competed for entry. Tyramine entry was unaffected by cooling, was not saturable and did not affect the entry of either NA or 5HT. NA and 5HT entered the erythrocytes at rates which were proportional to their lipid solubilities. 4. Metabolic inhibitors had no effect on amine transport. Inhibitors of amine transport in other tissues produced only small non-specific reductions of NA accumulation in the red cells. 5. Amine accumulation was a symmetrical process (no amine was retained by the red cells if the concentration gradient was reversed). It is concluded that NA and 5HT enter the cells by facilitated diffusion. The entry of NA and 5HT displayed countertransport, an additional feature of facilitated diffusion. 6. The relationship between the physical properties of the amines and the routes by which they entered the erythrocytes is discussed.


A study of the canine gastric action potential in the presence of tetraethylammonium chloride. 1. The effects of tetraethylammonium (TEA) ion on the action potential of isolated longitudinal muscle of the dog antrum were used to gain some insight into the mechanism of generation of the plateau potential of the action potential complex. The double sucrose gap was used. 2. In concentrations of TEA up to 5 mM, the amplitude of the upstroke potential was increased. In 10mM-TEA there was also an increase in the amplitude of the plateau potential and in the maximum rate of rise of the upstroke potential. 3. Concentrations of TEA (3 mM and greater) increased the duration of the action potential. Five mM-TEA produced spike potentials which occurred only during the plateau potential of the action potential. Each spike caused a contraction. 4. The steady-state voltage-current relation was studied in normal Krebs solution and in TEA containing Krebs solution. In normal Krebs solution the voltage response was not a linear function of the applied current when outward current pulses were used. In TEA solution the voltage response was a linear function of the entire range of applied depolarizing current. 5. In low concentrations of TEA (2-4 mM), when the steady-state voltage-current relation was linear, constant current pulses were applied between action potentials and during the plateau potential to determine if there were a decrease in membrane slope resistance during the plateau. It was found that the amplitude of the electrotonic potential recorded during the plateau was significantly less than the amplitude of the electrotonic potential recorded between action potentials. 6. The rate of repolarization of the plateau potential was studied in normal Krebs solution and in 2 mM-TEA Krebs solution. The rate of repolarization of the plateau potential was slowed in TEA Krebs solution. 7. It is concluded that there is an increase in the membrane conductance during the plateau potential. The repolarization following the plateau potential is due to a TEA-sensitive outward current.


Effects of simulated approval-seeking and avoiding on self-disclosure, self-presentation, and interpersonal attraction. Forty-eight undergraduate women assigned an approval-seeking or approval-avoiding role disclosed significantly more to a male listener (C) than did control Ss given no particular set, with no difference found between seeking and avoiding conditions in intimacy of disclosure. But content analyses indicated that approval-seeking Ss presented themselves significantly more positively, and approval-avoiding Ss significantly more negatively than did controls. These data supported the hypothesis that disclosure may serve as an instrumental affiliative act associated with both interpersonal approach and avoidance motives. The hypothesis that simulated attraction facilitates actual attraction was supported more clearly in analyses of Ss' liking ratings of C than in Ss' ratings of C's attractiveness or desirability as a dating partner. The latter findings are discussed in terms of intimacy implications of the attraction measures used.


Beneficial and detrimental modeling effects on creative response production. Enhancement of creativity through various educational "training" methods or external factors fostering creative production has long been demonstrated. The assumption has been that creativity exists as a given quantity in trait form, or that progressive learning takes place. Social observational modeling is investigated here as a technique that can both increase and decrease level of creative production in the individual despite every opportunity presented to respond freely and without (a) resort to any direct education or reinforcement methods or (b) the presence of environmental constraints. One hundred and twenty female university students were assessed for creativity on one figural and one verbal task of the Torrance Tests of Creative Thinking and the components of fluence, flexibility, originality, and elaboration. Ss then observed either high, low, or no figural creative model performance based on normative responses of past Ss and were reassessed on alternate test forms. Reassessment showed both predicted increases and decreases in component verbal creativity scores.


Sex differences in adolescent life stress, social support, and well-being. The present study compared male and female adolescents in terms of experienced life stress, social support recieved from parents and peers, and emotional and physical well-being. Ss were 93 male and 181 female adolescents obtained from three high schools. Data were collected by anonymous questionnaires. The results showed that female adolescents reported significantly greater life stress, and although they received significantly more social support from peers, they also reported significantly poorer emotional and physical well-being than males. An explanation for these findings in terms of difficulties in the socialization of female adolescents is proposed.


Some correlates of trust.

Some correlates of trust. Trust has been variously defined by behavioral scientists and not very thoroughly investigated. In this study trust was defined as an expectancy held by an individual that the behavior of another person or a group would be altruistic and personally beneficial. An attempt was made, using this conceptual definition, to identify some personality and behavioral correlates of trust. Seven interpersonal relations groups with approximately 10 male and female undergraduates per group were studied with use of the Janis and Field self-esteem inventory, Schutz's FIRO-B scale, and the Rotter internal-external scale. It was discovered that a trusted person is one who is highly influential, has an internal locus of control, a low need to control others, high self-esteem, and is open to being influenced by others.


Reflection-impulsivity and level of maturity. It was hypothesized that scores on the Matching Familiar Figures Test (MFF) are related to level of maturity. To test this hypothesis, 76 latency-aged boys in residential treatment were administered the MFF and a gross motor coordination test and were assessed for soft signs of neurological damage. Also included were age, IQ, and reading scores, along with ratings of behavior problems, activity, and impulsivity levels. A factor analysis yielded a factor (Factor II) consisting of MFF errors, age, soft signs of neurological damage, and gross motor coordination. Another factor (Factor IV) consisted of MFF errors and MFF latency. Factor IV provides support for the reflection-impulsivity construct, while Factor II may suggest that scores on the MFF are partially a function of physiological maturity and that errors contribute more than latency to the determination of reflection/impulsivity.


The unitary construct variously named overinclusion and cognitive style. To assess the relationships among field dependence, overinclusion, and retardedness, 87 individuals were administered Epstein's Overinclusion Test, the Embedded Figures Test, and two tests of retardedness--the O'Connor Finger Dexterity Test and a word association test. Ss included both males and females: 21 noninstitutionalized controls solicited via newspaper advertisements, 23 recently admitted and 21 long-term non-paranoid schizophrenics, and 22 recently admitted individuals with affective disorders. Results supported the direct relationship between overinclusion and field dependence. Sex differences appeared on these same two tests. Contradictory to the third hypothesis, the two tests of retardedness were directly related to both overinclusion and field dependence. These two latter concepts may therefore be manifestations of a single more comprehensive construct.


Locus of control and teacher ratings of behavior problems in preschoolers. The present study investigated the relationship between internal-external control and behavior adjustment in 25 preschool boys and girls. Ratings were completed by the preschool teachers on 11 specific indices of behavior adjustment as observed in school. Results were nonsupportive and, in fact, were contrary to the general hypothesis that high external locus of control would be positively related to greater behavior adjustment problems, as has been found with some groups of older children and adults. Results revealed the need for more longitudinal research investigating the developmental changes of such relationships. The usefulness of employing more specific behavior problem indices rather than a general measure of adjustment-maladjustment was also demonstrated.


Focal point location and inversion perception among New Zealand Maori and Pakeha children at two age levels. The purpose of the investigation was to determine whether differences in focal point dependency in inversion perception exist among New Zealand Maori (N = 42) and Pakeha (N = 44) boys and girls at two age levels. Ss were five- and eight-year-old children individually exposed to 12 figure pairs. The task was to indicate one figure of each pair as appearing upside down. Significant focal point dependency was exhibited for all groups (p less than .01). Significant differences in focal point dependency were found between five- and eight-year-old Pakeha children (p less than .025) and between eight-year-old Maori and eight-year-old Pakeha children (p less than .05).


Moral judgment in retarded and nonretarded school age children. The moral judgment of 135 normal, educable retarded, and trainable retarded boys and girls (ages 6-10, 11-13, and 14-16) was individually assessed to determine the significance of chronological age and IQ on moral development. The results indicated significant differences in mean normal judgment between the groups and each age level. The findings were interpreted as substantiating Piaget's stage theory of moral development and suggesting that within the retarded population, level of intellectual ability is also significantly related to moral judgment.


Hospitalized chronic alcoholic patients without field-dependent performance in the rod-and-frame test. Hospitalized male chronic alcoholics (n = 60) fully employed and with no history of malnutrition were compared with matched nonalcoholic controls (n = 50) on the Rod-and-Frame Test (RFT). The RFT scores of the alcoholics were not significantly worse than those of the controls. This is in marked contrast to earlier reports of RFT field dependence in unemployed, indigent alcoholics and supports Burdick's findings with the Embedded Figures Test.


Physical attractiveness and personality development. A test of the relationship between physical attractiveness and ego development was completed through an interview study of 294 men and women college students. Ss responded to personality measures assessing identity formation, locus of control, and ego functioning and were rated on facial attractiveness and body form scales. Contrary to the physical attractiveness stereotype, attractive and unattractive Ss did not differ in their personality styles.


Work-related motives and self-esteem in American women. Acknowledging the need for additional research on work-related motives and self-esteem in American women, this study investigated the hypothesis that women with a favorable self-esteem would score high in n Ach, in Pow, and n Auto, whereas women with a less favorable self-esteem would score high in n Aff, n Agg, and n Def. Eighty-five female college students completed Gough and Heilbrun's Adjective Check List and Form B of the Coopersmith Self-Esteem Inventory. Data were analyzed by means of chi square tests in conjunction with the coefficient of association asymmetric lambda. The results indicated that, as predicted, women with a favorable self-esteem scored high in n Ach (p less than .001) and n Pow (p less than .001), while contrary to expectation, they also scored high in n Aff (p less than .05). All other relationships were found to be nonreliable. These findings were interpreted as stressing the importance of the relationship between self-esteem and work-related motives in women.


Aggression, performance variables, and anger self-report in ice hockey players. This study partially replicated a former one showing a relationship between aggression and performance among hockey players. With certain penalties used as a measure of aggression, two groups of male college ice hockey players were compared for differences in goals and assists. Those rated high in aggression scored significantly more goals than those low in aggression. The direction of differences in assists was the same but did not reach significance. When the same groups were compared for shots on goals, significant differences were found, favoring the high aggressive group. This findings was discussed in light of energy output and efficiency. Attempts to relate performance and personality measures were not successful when comparisons on a self-report measure of anger were analyzed.


[Results of lymphography in 13 cases of onchocerciasis]. Systematic lymphographic studies in 13 cases of infection with Onchocerca volvulus have enabled a "lymphographic diagram" to be made for each infected patient. The images obtained are similar to those observed in wuchereriasis. The microfilariae in onchocerciasis, however, are not transmitted in the lymphatic system, and the lesions, which vary according to the degree of infestation, show little progression. They are found mainly in the inguino-crural ganglia which are the first main ganglionic relay system for the lower limbs.


[Experimental study of intensifying screens used in diagnostic radiography (author's transl)]. A physical experimental study of intensifying screens for diagnostic radiography was set up. Experimental conditions were identical with those of medical practice. Spectra speeds of several films and spectral emission of intensifying screens were built up. Speeds of screen-film combinations, as well as definitions, were measured. Results are available to range the different screens-film systems after their speed factor, at 40, 70 and 120 kV, with mention of definition of these systems. It so objectively appears that rare-earth intensifying screens make possible a decrease of X-ray exposure for patient under a factor 2 to 2,5 and a less early wearing of apparatus, namely of X-ray tubes.


Clinical study of recurrence rate and survival time of patients with carcinoma of the breast treated by biopsy excision without any other therapy. We report the recurrence rate and survival time in 31 patients with carcinoma of the breast who were treated by limited excision of the primary tumour and no other therapy. At three years the overall recurrence rate in the breast was 28%. One patient was found to have systemic disease and two died of other causes. The overall recurrence rate in the breast at five years was 33%. One patient died of disseminated disease at 6 years 4 months.


Continent ileocaecal urinary reservoir.

Continent ileocaecal urinary reservoir. In 14 cases, a continent ureteroileocaecal urinary reservoir has been constructed. If a long-term ease of self catheterization can be maintained, some patients requiring an urinary diversion might prefer an appliance-free urinary reservoir to a freely draining conduit and urinary appliance. The indications and place for the continent urinary reservoir still need to be studied, modified and proven during the coming years.


Synthesis and biological evaluation of 10-oxa-11-deoxyprostaglandin E1 and 10-nor-9,11-secoprostaglandin F1 and their derivatives. Three 10-oxa-11-deoxyprostaglandin E1 and two 10-nor-9,11-secoprostaglandin F1 analogues were prepared. The compounds were evaluated for pregnancy interruptions, oxytocin-like activity (uterine strip), and antiprostaglandin activity. One of the 10-nor-9,11-secoprostaglandin F1 analogues displayed activity as a PGE2 antagonist in the gerbil colon smooth muscle preparation.


Synthesis and antiarrhythmic activity of 2-dialkylaminoalkyl-9-phenyl-1H-indeno[2,1-c]pyridine derivatives. Some dihydro- and hexahydro-2-dialkylaminoalkyl-9-phenyl-1H-indeno[2,1-c]pyridines were prepared and found to possess significant antiarrhythmic activity. Hydrogenation of the dihydro compounds 4 produced the allcis-hexahydro isomers 5 which were consistently active in three assays against induced ventricular arrhythmias. On the other hand, the H9H9a-trans isomers, which were obtained by basic equilibration of the cis isomers, were less effective.


Synthesis of O-alkylated lysine-vasopressins, inhibitors of the antidiuretic response to lysine-vasopressin. [Mpa1,Tyr(Et)2]-LVP (1-deamino-2-O-ethyltyrosine-8-lysine-vasopressin), [Mpa1,Tyr(n-Pr)2]-LVP, [Tyr(n-Bu)2]-LVP, [Mpa1,Tyr(n-Bu)2]-LVP, and [Mpa1,Tyr(n-hexyl)2]-LVP were synthesized in solution by the p-nitrophenyl ester method. The previously prepared [Tyr(Et)2]-LVP was resynthesized. All compounds possessed weak agonistic properties in both antidiuretic (0.5-2.0 IU/mumol) and pressor (0.5-3.0 IU/mumol) assays. In the rat none of the analogues inhibited the antidiuretic action of LVP when the two substances were given together in a single injection. However, when administered in low subthreshold doses, most of the deamino compounds suppressed the antidiuresis induced by a continuous infusion of LVP. Complete inhibition was obtained with [Mpa1,Tyr(Et)2]-LVP. The antagonistic potency seemed to decrease with increasing size of the alkyl substituent and [Mpa1,Tyr(n-hexyl)2]-LVP showed no antagonism. The molar inhibitor-LVP ratio for maximal inhibition was well below 100. Neither of the two amino analogues showed a clear-cut antagonism in the antidiuretic assay. Furthermore, none of the reported compounds was antagonistic to LVP in the rat pressor assay.


Discriminant analysis and structure-activity relationships. 1. Naphthoquinones. Discriminant analysis has been used to study the data for naphthoquinones as antitumor agents in three different animal tumor systems. In each case the most significant variables for classifying the compounds into two groups according to their antitumor activities were determined by a stepwise procedure. The usefulness of discriminant analysis in the design of drugs is discussed.


Effects of molecular modification on hypocholesteremic activity of 1,3-bis(substituted phenoxy)-2-propanones and related derivatives. A series of 1,3-bis(substituted phenoxy)-2-propanones, long-chain ketones, and related derivatives has been synthesized, and it has been found that certain analogues produce significant lowering of serum cholesterol levels in Sprague-Dawley rats. These compounds possess no estrogenic properties and are nontoxic at 10 mg/kg/day. Physical studies on these compounds include an attempt to correlate hypocholesteremic activity with the lipophilic, electronic, and steric properties of the compounds. The 1-octanol-H2O partition coefficient was measured for certain derivatives and the pi constant for the substituents was calculated. Hammett's sigma constants for aromatic substituents were obtained from the literature. The only correlation found to exist is between hypocholesteremic activity and steric size and position of the aromatic substituents in the propanones.


Potential organ or tumor imaging agents. 16. Fluorinated androstanes and the prostate. A series of substituted 5alpha-androstan-17beta-ols was synthesized and evaluated for their potential use in the development of a prostate imaging agent. The ability of the synthesized compounds to compete with [3H]-5alpha-dihydrotestosterone for rat prostate androgen receptor protein served as the screening assay. For 3-substituted derivatives, the order of binding to the androgen receptor protein was =O greater than -OH greater than H approximately or equal to F. 3beta-Fluoro-5alpha-androstan-17beta-ol was found to have approximately 5% the androgenic activity of testosterone propionate in the castrated rat. The low biological activity for the 3beta-fluoro derivatives, coupled with the synthetic obstacles associated with introducing fluorine-18, has led us to search for more suitable halo steroids as potential radiodiagnostics.


Ferrocenyl polyamines as agents for the chemoimmunotherapy of cancer. A series of ferrocenyl polyamines, compounds intended to bind to the tumor cell surface nucleic acid and elicit an immune response, was synthesized and screened for antitumor activity. Target ferrocenyl polyamines 1a,b,2, and 3, bearing 2-, 3-, and 4-amino groups, respectively, were readily obtained in yields of 31-58% from their corresponding ferrocenyl polyamides (5a-d) by reduction with diborane in THF; lithium aluminum hydride was not an effective reducing agent in this case. Although the target compounds failed to prolong the life ofmice with P-388 lymphocytic leukemia, three of the intermediate amides (5b-d) did exhibit low but significant activity (T/C = 123, 132, and 120%, respectively).


2,3-Dihydroxy-9-amino-9,10-dihydrophenanthrene, a rigid congener of dopamine and isoapomorphine. A rigid dopamine congener, 2,3-dihydroxy-9-amino-9,10-dihydrophenanthrene, was synthesized and tested for the ability to dilate the renal artery in dogs. The compound was found to be inactive in this assay at molar doses 1000 times greater than required for dopamine. This result is similar to isoapomorphine. The title compound was also examined for its ability to stimulate rat striatal adenylate cyclase. In concentrations of 10-100 micrometer no effect was observed. The phenanthrene also showed no ability to block dopamine-induced stimulation of adenylate cyclase.


Antitubercular 2,8-bis(alkylaminomethyl)phenazines. The preparation and antitubercular properties of a series of 2,8-bis(alkylaminomethyl)phenazines are described. These compounds all inhibited the growth of Mycobacterium smegmatis ATCC 607 in vitro. 2,8-Bis(dibutylaminomethyl)phenazine (5c) was also active against a lethal Mycobacterium tuberculosis H37Rv infection in mice.


2-(Alkoxyaryl)-2-imidazoline monoamine oxidase inhibitors with antidepressant activity. Unlike the related noncyclic amidines which are broad-spectrum cestocides, a number of 2-imidazolines substituted in the 2 position by alkoxyaryl groups were not highly active in screening tests against the mouse tapeworms Hymenolepsis nana and Oochoristica symmetrica. Certain of the 2-(4-alkoxynaphthyl)-2-imidazolines and 2-(6-alkoxy-2-naphthyl)-2-imidzolines, however, had activity interpreted as antidepressant in the mouse. This activity paralleled in vitro irreversible inhibitory activity against mouse brain MAO for those where no substitution is present on the imidazoline ring. This irreversibility probably has a different origin from that postulated to explain the irreversible MAO inhibition of proparglic, cyclopropyl, and other "chemically reactive" MAO inhibitors.


Voltage-gated cation conductance channel from fragmented sarcoplasmic reticulum: steady-state electrical properties. The interaction of fragmented sarcoplasmic reticulum (SR) with an artificial planar phospholipid membrane under conditions known to induce fusion of phospholipid vesicles raises the conductance of the planar bilayer by several orders of magnitude. Measurements of steady-state electrical properties of bilayers thus modified by SR show that two types of conductance pathways are present. One is a voltage-independent pathway which may be somewhat anion-selective. The other is a voltage-gated ionophore showing selectivity to small monovalent cations. This latter ionophore is fully oriented within the artificial bilayer and is inhibited asymmetrically by divalent cations. It is also inhibited below pH6. The ionophore displays single-channel conductance fluctuations between two states. "open" and "closed", with an open-state conductance of 1.4 x 10-10 mho in 0.1 M K+. The physiological function of this ionophore is unknown.


Activity coefficients of intracellular Na+ and K+ during development of frog oocytes. The chemical activities, (a), of Na+ and K+ were determined in large mature and in small immature frog oocytes, using open-tipped micropripettes and ion-selective microelectrodes. The average chemical concentrations, c, of Na+ and K+ were determined by spectrophotometry and by electron probe X-ray microanalysis. The apparent activity coefficient (gammaapp) was calculated for each ion as the ratio, a/c. With development, (aNa/ak) decreased four to fivefold and (cNa/cK) increased six to sevenfold. In the large mature oocytes, gammaapp was measured to be 0.08 +/- 0.02 and gammaappK lay within the range 1.15 +/- 0.03 to 1.29 +/- 0.04, constituting the smallest value for Na+ and largest value for K+, respectively, thus far reported. This intracellular value of gammaappK was substantially greater than the activity coefficient of K+ in the external medium (0.76). The data suggest that the inequality of gammaappNa and gammaappK in this and probably other cells reflects the development of subcellular compartmentalization of ions. Possible intracellular sites of ionic compartmentalization are considered.


Kinetic properties of electrostatic pores with orientable dipoles, for Na+ and K+ transport through biological membranes. The model, used previously to account for the transport of K+ ions through squid axon membranes under steady-state conditions, is extended to the description of the kinetic behavior of Na+ and K+ currents, for sudden variations of the applied potential. Theoretical curves are obtained by numerical integration of the electrodiffusion equation for ions within pores, with variable boundary conditions resulting from a progressive reorientation of dipoles at the pore surface. The pores are supposed to be selective and the dipole parameters are allowed to be different for Na+ and K+ pores. The K+ current varies with time, in agreement with the K+ dipole parameters deduced from the steady-state results of Gilbert and Ehrenstein (1969). The dipole parameters for Na+ current are deduced from the steady-state results of Armstrong, Bezanilla & Rojas (1973), where the inactivation phase of the Na+ current is suppressed by introducing pronase in the inside solution. The dipole reorientation is relavent to explain the sigmoid shape of the activation phase of the Na+ current, while the inactivation phase seems to resort to another physical mechanism. The predictions based on this model agree with the experimental results for the steady-state negative resistance and the gating current, associated both with a reorientation of surface dipoles, as well as the activation phase of the Na+ current using a consistent set of parameters for all these comparisons.


Quercetin inhibits hexose transport in a human diploid fibroblast. The flavonol quercetin, a phloretin analog, inhibits transport of 2-deoxyglucose and 3-O-methylglucose in a cultured human diploid fibroblast. This inhibition is related to transport itself and not to the reported effects of flavonoids on membrane-bound ATPases. From concentration-inhibition curves at several pH's we conclude that uncharged (acid) quercetin (pK = 7.65) is the inhibitory form of the molecule (K1 = 10micron). Quercetin, unlike phloretin, is rapidly degraded in 0.1 N NaOH; the degradation products are weakly inhibitory to hexose transport.


A chamber attached to the SEM for fracturing and coating frozen biological samples. A chamber for introducing, fracturing and coating frozen biological samples has been developed as an attachment to the sepcimen chamber of a scanning electron microscope. Together with a eucentric-tilt cold-stage, this chamber constitutes a complete system for viewing fractured biological surfaces of the type normally only seen by replica techniques. An air-lock on the chamber accepts a transfer module to allow insertion of the frozen sample without frost build-up. Fracturing is carried out with a precisely adjustable cooled knife under a 10--100X binocular microscope. The sample can tilt and rotate while being coated with carbon or metals evaporated from rechargeable sources introduced through the air-lock. Cooling in the chamber is provided by a cylindrical copper tank filled with liquid nitrogen. The chamber has its own LN2 trapped high vacuum system. After preparation the sample can be placed directly into the SEM through an isolation valve. The cold-stage utilizes a Joule-Thomson refrigerator. The sample can be kept below 103 K at all times though there are provisions for heating it in the fracturing and cold-stage positions. A system of controls, sensors and interlocks simplifies the operation of the system.


Interference reflection microscopy of adhesion of Amoeba proteus. A simple method of observing the adhesive behaviour of large cells by means of interference reflection microscope is described, and some observations of monopodial Amoeba proteus are presented. Amoebae may contact with the substratum at any point along the long axis of the cells. Points of contact are usually few, small and temporary. Frequently the cell surface within the contact points oscillates, changing the separation distance from the substratum.


Electron microscope fluoro-autoradiography: improvement of efficiency. The fluorographic process for enhancement of the autoradiographic detection of beta-ray emitted by tritium has been successfully adapted to electron microscope autoradiography. An original scintillator plastic film helped to increase the detection yield of electrons up to 80% without alteration of the morphological aspect of the autoradiograms, and without increasing background fog or causing apparent loss of resolution.


A simple and inexpensive culture device for cell growth, quantitative microscopy and autoradiography. An inexpensive culture chamber suitable for subsequent preparations for cytochemical or radiographic work is demonstrated. The chamber consists of two glass microscope slides suitably prepared for cell growth and a gasket of silicone rubber. The slides and gasket are sealed and held together with two ordinary spring letter clips or clothes-pins. Cells may be inoculated by piercing the gasket with a hypodermic needle, or by removing the top slide and adding cells directly. Long-term cultivation with medium replacement is easy and efficient and addition of isotopes or other materials may be done aseptically.


Comparison of age-specific mortality from breast cancer in males in the United States and Japan. Mortality data on breast cancer in males from the United States and Japan were analyzed. The logarithm of the mortality rate increased in a linear fashion with the logarithm of age and had a slope of about 5. Mortality in Japan was about one-fourth that in the United States, but the relationship to age was similar.


Cancer incidence in a religious isolate of Alberta, Canada, 1953-74. Members of a religious isolate who live in approximately 240 farming colonies in the Canadian prairie provinces and the United States border states were studied. The sect's 6,700 members living in the province of Alberta, Canada, comprise more than 30% of this sect's population of North America. The numbers of their cancer cases ascertained from 1953 to 1974 in Alberta were compared to those expected from Alberta Cancer Registry rates. The overall incidence of registered cases of cancer among the religious isolate's females was significantly less than expected (48 observed, 74.2 expected), and in the males the overall incidence of cancer did not differ from that expected (52 observed, 56.5 expected). Significantly fewer cases of lung cancer than expected were found in males, and significantly fewer cases of carcinoma in situ of the cervix uteri were found in females. Finally, significantly higher incidence of stomach cancer was found in the sect's males. Data on a family with two cases of stomach cancer contributed to this observed excess of stomach cancer.


Correction of modal DNA values obtained by microspectrophotometry and tests for their shifts. The technical problems in the application of statistical analyses of the nuclear DNA contents measured by plug or two-wavelength Feulgen microspectrophotometry were discussed. The skewness of the nuclear DNA content unimodally distributed in a cluster could be corrected by logarithmic transformation. A mean value of the logarithmically transformed DNA contents was a more logical characterization of cancer than a graphically obtained mode of nontransformed values. Equations were derived to estimate the number of cells in the G1- and S-phases of mitotic cycles contained within the cluster and to estimate the correction factor of the mean of transformed values of cells in the G1-phase. Thus statistical tests for a shift in the nuclear DNA content of the cells in question in the G1-phase from that of control cells were made possible.


Spontaneous human mononuclear cell cytotoxicity to cultured tumor cells: reproducibility of serial measurements with the use of a chromium-51-release microcytotoxicity assay. Twenty-three healthy human adults with naturally occurring (spontaneous) mononuclear cell cytotoxicity (MCC) to cultured human tumor cells were evaluated in a serial study over 23 months to determine whether their initial MCC levels remained stable. A 3-hour 51Cr-release microcytotoxicity assay, in which the HBT-3 cancer-derived cell line with HeLa markers and the ALAB breast cancer-derived cell line were used, was standardized and its suitability for such serial studies was evaluated. The data showed that the 51Cr-release assay is reproducible and suitable for use in serial studies of MCC. The intrinsic technical error for a single assay averaged 12.5% (2-26%) coefficient of variation. The greatest sources of technical variation with time were the passage level of the target cells and the temperature at which the effector cells were stored and handled. When these technical factors were controlled, naturally occurring MCC was fairly reproducible with time. Of the healthy individuals with initial high or low MCC levels, 61% tended to retain these levels in a stable fashion, but the remaining 39% studied showed fluctuations of MCC greater than 33% coefficient of variation.


Morphologic evidence for retrovirus production by epithelial cells derived from a human testicular tumor metastasis. Ultrastructural examination of primary and subcultured epithelial cells established in vitro from an abdominal metastasis of a human testicular tumor revealed particles with the morphology of retroviruses. These structures, found only after extensive scanning of the cells, were observed budding from microvilli and from the outer cell membrane and as extracellular particles. Production of these virus particles was stimulated by the incubation of cells in culture medium containing 5-iodo-2'-deoxyuridine and dexamethasone.


Synergistic cytotoxicity for L929 cells of polyriboinosinic-polyribocytidylic acid and amphotericin B methyl ester. A synergistic impairment in cell growth of L929 mouse fibroblasts resulted from treatment with a combination of amphotericin B methyl ester and polyriboinosinic-polyribocytidylic acid. This effect, which may result from the altered membrane permeability induced by polyenes, may augment the therapeutic efficacy of polyribonucleotides as antitumor compounds.


Production of adenocarcinomas of the small intestines of Wistar rats fed panfuran-S containing 3-di(hydroxymethyl)amino-6-(5-nitro-2-furylethenyl)-1,2,4-triazine. Panfuran-S in the diet produced a high incidence of invasive and metastatic adenocarcinomas of the duodenum and the jejunum in outbred Wistar rats. Depressed growth and incidence of cancer production were dose-dependent. Adenocarcinomas of the duodenum were present in 2 of 18 (11%) rats that received 1,750 ppm 3-di(hydroxymethyl)amino-6-(5-nitro-2-furylethenyl)-1,2,4-triazine (DHNT) in the diet and in 11 of 19 (58%) rats that received 3,500 ppm DHNT. Adenocarcinomas of the jejunum were present in 10 of 18 (56%) and 16 of 19 (84%) rats that received 1,750 and 3,500 ppm DHNT, respectively, for 35-37 weeks. The only other tumors observed were squamous cell papillomas of the forestomach. Histologically, most of the adenocarcinomas appeared tubular or papillary and were similar to adenocarcinomas in the small intestine of man and also to human intestinal-type adenocarcinoma of the stomach. This system provided a useful experimental model for the study of the pathogenesis of carcinoma of the small intestine.


Mammary nodules in beagle dogs administered investigational oral contraceptive steroids. Of 172 beagle dogs administered oral contraceptive steroids for 5-7 years, 114 developed 1,156 nodules in the mammary gland region. Most of these nodules arose 2.5-3.5 years after initiation of treatment. Approximately 16% of the nodules were transient and disappeared spontaneously from the mammary gland during the study. A total of 925 nodules were present in 99 dogs at the time of death or necropsy. These nodules were classified as benign mammary dysplasias (7.0%), lobular or intraductal hyperplasias (31.4%), simple adenomas (20.8%), complex adenomas (25.4%), benign mixed tumors (5.3%), malignant tumors (3.6%), or nonmammary lesions (6.5%). Histologically, the mammary nodules were representative primarily of the hyperplasias and tumors that occur spontaneously in the mammary glands of the dog. The only major exception was the presence of 82 simple adenomas that had basaloid features. Most of the contraceptive-related mammary nodules developed in dogs receiving the combination of progestion and mestranol at 10 or 25 times the proposed human dosage. Control dogs and dogs receiving mestrenol alone had few mammary nodules. Combinations of anagestone acetate and mestranol and chloroethynyl norgestrel (WY-4355) and mestranol produced large numbers of nodules at 10 and 25 times the proposed human dosage, whereas ethynerone plus mestranol produced large numbers of nodules only at 25 times the proposed human dosage. Ethynerone, when given alone at 25 times the proposed human dosage, was associated with fewer mammary nodules. Malignant neoplasms were seen in dogs given 10 and 25 times the proposed human dosage of anagestone acetate plus mestranol and 25 times the proposed human dosage of WY-4355 plus mestranol and ethynerone plus mestranol. This study strongly associates certain combinations of progestin and mestranol with mammary neoplasia in dogs.


In situ Fc receptor-bearing cells in two murine tumors. I. Isolation and identification. The in situ inflammatory response was studied in 2 different tumors, the T1699 mammary adenocarcinoma in inbred DBA/2 mice and a sarcoma induced in inbred C57BL/6 mice by murine sarcoma virus. The presence of Fc receptors (FcR's) on infiltrating host cells was determined by rosette formation with antibody-coated sheep red blood cells (EA). Differences in FcR-binding activity among various cells were detected with the use of EA prepared with a range of antibody concentrations. Cells bearing FcR represented one-third or more of the inflammatory cell population in both tumors. The FcR-positive cells were heterogeneous in regard to both cell type and FcR activity. Monocytes and macrophages had greater FcR activity than did lymphocytes. Different populations of FcR-positive cells could be isolated by their EA-binding characteristics.


Involvement of chromosome No. 2 in chromosome changes in primary leukemia induced in rats by N-nitroso-N-butylurea. Cytogenetic studies were done on 34 primary leukemias induced by N-nitroso-N-butylurea (NBU) in outbred Long-Evans rats. The results revealed leukemia cells with No. 2 trisomy and long No. 2 chromosome, which characterized the leukemias induced by polycyclic hydrocarbon carcinogens such as 7,12-dimethylbenz[a]anthracene and 7,8,12-trimethylbenz[a]-anthracene. These findings suggest a common mode of action of different carcinogenic chemicals at the chromosome level, although the lower incidence of these chromosome changes and of erythroblastic leukemias with NBU suggests subtle difference in their actions.


Histogenesis of symmetrical 1,2-dimethylhydrazine-induced neoplasms of the colon in the mouse. CF-1 female adult mice were given weekly sc injections of 20 mg symmetrical 1,2-dimethylhydrazine (DMH)-2HCl/kg body weight and killed at various intervals after commencement of the injection. [3H]thymidine (TdR) was given before the animals were killed. The histogenesis of colon neoplasms was investigated by means of autoradiographs prepared from sections of Epon-embedded descending colon, which were stained with periodic acid-Schiff reaction and iron hematoxylin. By 9 weeks after initiation of DMH treatment, the distal 5 cm of the colon became enlarged, the mucosa thickened, and the crypts were elongated and hyperplastic. In the hyperplastic crypts, the number of proliferating cells increased, but the distribution of these cells followed a previously discussed slow cut-off model of Cairnie et al. as for the normal crypts. Differentiation and transformation of epithelial cells occurred, but somewhat aberrantly. Hyperplasia of the crypts occurred diffusely, but neoplastic lesions that began to appear by 9 weeks after the intiial treatment were isolated. An isolated crypt from which a neoplasm developed was first repopulated by what appeared to be altered, undifferentiated "stem" cells. These cells did not differentiate, continued to divide, and eventually upon migration accumulated in the upper part of the crypts, where an earliest identifiable neoplastic lesion was observed. Once such a lesion was formed, it expanded in various directions, depending on the local environments, and formed a polypoid or discoid lesion. The biologic behavior of the neoplasm seemed to be determined by the downward progression of its leading edge. When it penetrated the muscularis mucosae, the neoplasm became highly invasive. In the murine model, the invasive adenocarcinomas were observed by 26 weeks after commencement of DMH treatment.


Resistance to syngeneic lymphoma cells as a result of immunization with chemically modified allogeneic lymphoma cells in mice. Immunization with trinitrophenyl (TNP)-derivatized allogeneic lymphoma cells resulted in significant immunity to poorly immunogenic syngeneic lymphoma cells. Neither TNP-treated nor X-irradiated syngeneic lymphoma cells were immunogenic under similar experimental conditions. Immunization with untreated allogeneic lymphoma cells produced only minimal levels of resistance to challenge with syngeneic lymphoma cells. The complete set of antigens responsible for the immunity was carried exclusively on transformed lymphocytes because allogeneic TNP-derivatized lymph node and thymus cells also did not immunize. The immunity was transferred to nonimmune inbred BALB/c and A/J mice by spleen cells from immune donors. The Winn assay was used to measure the antilymphoma immunity in vivo. When immune spleen cell-lymphoma mixtures were inoculated sc at a ratio of 1,000:1, nonimmune mice were completely protected. Reactivity of immune lymphocytes to syngeneic lymphoma cells was also demonstrated in vitro by the 51Cr-release method. Immunization with TNP-derivatized allogeneic lymphoma cells resulted in measurable immune resistance to inocula of viable syngeneic tumor cells in excess of 100 times the tumorigenic dose. Induction of immunity to syngeneic lymphoma cells strictly required that the immunizing cells be histoincompatible at the major H-2 locus and possess tumor-specific antigen(s). Maximum immune sensitivity was observed only after chemical modification of the immunizing allogeneic lymphoma cells.


Mouse natural cell-mediated cytotoxicity to human leukemia: independence of serum source used for target-cell culturing and cytotoxicity assay. Human hematopoietic target-cell lines known to be lysable in short-term 51Cr-release assays by natural killer (NK) cells occurring in spleens of normal, nonimmune CBA/J and A/J mice were adapted to grow in culture medium supplemented with human AB serum or with normal mouse serum (NMS). After a culture period of more than 8 weeks, the resulting AB serum- or NMS-grown sublines exhibited the same degree of sensitivity to mouse NK cells in direct or competition assays as the original lines kept in fetal calf serum. Susceptibility of the various target cell lines was also independent of the type of serum supplement used during the cytotoxicity assay. Preabsorption of the serum supplement with in vitro cultured cell lines identical to the target cells left NK cytotoxicity to these lines intact. In this heterologous system, no changes in the expression of NK relevant target structure(s) could be detected in sublines grown in sera from different species, but target susceptibility seemed to be preserved.


Immunologic studies on a pancreatic oncofetal protein. Immunization of rabbits with a human fetal pancreas extract produced precipitating antibody against an antigen present only in fetal pancreas and extracts of human pancreatic carcinoma. Pancreatic oncofetal protein (POP) migrated on immunoelectrophoresis in the alpha1-alpha2 region, thus making possible its detection by counterimmunoelectrophoresis. POP was found in the 12,000 X g supernatant of fetal pancreas and could be precipitated with (NH4)2SO4 at concentrations between 30 and 45%. The antigen was partially purified by consecutive centrifugation at 12,000 X g, 40% (NH4)2SO4 precipitation, and ion-exchange chromatography. Treatment of the POP with trypsin completely abolished its antigenic activity; this suggested that the antigen was a protein or a moiety closely associated with protein.


Cytology and quantitative cytochemistry of a poliferative atypical hemocytic condition in Mytilus edulis (Bivalvia, mollusca). Proliferative lesions were found in 16 of 994 Mytilus edulis mussels obtained from the mouth of the River Lynher at Plymouth, England. These lesions were characterized by infiltration and replacement of the connective tissue by enlarged, atypical, mitotically active, basophilic, hemocyte-like cells. Cytologic examination indicated the involvement of two cell types in this disorder, both of which were similar in appearance to the much smaller, normal basophallic agranular hemocyte. The abnormal cells were rich in cytoplasmic RNA and had significantly higher DNA levels than normal hemocytes as determined by scanning microdensitometry. A few of the atypical cells contained small cytoplasmic granules that were positive for lysosomal hydrolases. This condition was observed sequentially from what is believed to be the earliest stage of the disease, in which only a few atypical cells were present, to the terminal stage, in which the connective tissue was almost completely replaced and the digestive gland cells were necrotized. Some potentially carcinogenic aromatic hydrocarbons have been identified in the substrate of the mussel bed by gas-liquid chromatography-mass spectrometry analysis.


Effects of combined radiotherapy and immunotherapy with the use of pyran copolymer on murine fibrosarcoma. A weakly immunogenic, 3-methylcholanthrene-induced, subcutaneous fibrosarcoma syngeneic to inbred C3H/HeJ mice was used. Pyran copolymer was injected either directly into the tumor, ip, or iv as soon as tumors appeared or when tumors were 8 mm in diameter. One, three, or five doses of pyran copolymer at 10 or 20 mg/kg/dose were injected, with multiple doses being given every other day. Pyran copolymer injected intratumorally once, three times, or five times significantly retarded tumor growth and prolonged the survival times of the hosts. Of the other routes and doses, only pyran copolymer given three times iv significantly retarded tumor growth, but none of these significantly prolonged the survival times of the hosts. Pyran copolymer alone did not induce any complete regression of tumor. Local tumor irradiation with a single exposure to 2,000 rads of X-ray induced complete regressions in some mice, but a higher percentage of tumor cure was observed when tumor irradiation was followed by pyran copolymer treatment.


Dose response to intrarectal administration of N-methyl-N-nitrosourea and histopathologic evaluation of the effect of two retinoids on colon lesions induced in rats. Male F344 rats, 8 weeks of age, were given 16 intrarectal administrations of N-methyl-N-nitrosourea (NMU) at one of three dose levels over a period of 8 weeks. Five days after the final NMU instillation, rats were placed on one of three diets: chow with gelatin beadlets, chow with beadlets containing 0.024% 13-cis-retinoic acid, or chow and beadlets with 0.006% of the trimethylmethoxy phenyl analog of retinoic acid ethylamide. Groups of 20-40 rats were killed at 22-26 weeks after the first carcinogen treatment. The number of rats with colon carcinoma and the number of tumors per rat were dose related. In addition, "blind" histopathologic evaluation of four predesignate colon locations revealed a dose-related incidence of microscopic preinvasive and invasive colon carcinomas. The feeding of diets containing these two retinoids did not significantly alter the incidence of these parameters of carcinogenesis or the mean histopathologic score at predesignated colon locations for preinvasive or invasive neoplastic lesions. Over 90% of the colon neoplasms induced were invasive tubulopapillary adenocarcinomas. The diameters of the tumors correlated significantly with degrees of invasion of the colons. Only 1 tumor (a signet ring carcinoma) metastasized to the peritoneal cavity. Only 2 of 300 rats treated with NMU had tumors at sites other than the colon.


Antitumor of a boiled scallop extract.

Antitumor of a boiled scallop extract. A fraction from a boiled scallop extract modified by a sonication procedure exhibited marked antitumor activity when it was injected intradermally into either ICR or C3H/He mice that had been given sc implants of sarcoma 180 and Ehrlich carcinoma. The active moiety was heat-stable and noncytotoxic. In contrast, preparations from raw scallop showed lower antitumor activity and were heat-labile.


Effect of bile acids and neutral sterols on benzo[a]pyrene-induced tumorigenesis in skin of mice. The effect of neutral sterols and bile acids were determined in the classic mouse skin tumor induction system by applying each sterol or acid with benzo[a]pyrene to the skin of Swiss mice three times per week for 60 weeks. The mice were killed 63 weeks after the experimenta was begun. Most of the chemicals had an inhibitory effect on skin tumor formation by benzo[a]pyrene. Unconjugated bile acids had higher inhibitory action than did conjugated bile acids. The inhibition decreased in the following order of acids: chenodeoxycholic, lithocholic, deoxycholic, and clinic. Within the group of conjugated acids, taurine conjugates were more effective inhibitors than were glycine conjugates. The neutral sterols cholesterol, coprostanol, and coprostanone showed relatively similar, moderate inhibitory effects.


Incidence of spontaneous ileocecal immunocytomas in hybrids of LOU/C rats and rat strains with low spontaneous tumor incidence. Monoclonal immunoglobulin-secreting tumors (immunocytomas or plasmacytomas) appear in many species, but they occur at a low incidence and usually originate in lymphoid tissues. However, in the rat, the incidence of malignant spontaneous immunocytomas (or plasmacytomas) was high and the tumors consistently arose in the ileocecal lymph nodes. In inbred LOU/C/Wsl rats, these immunocytomas developed in twice as many males (31%) as females (16%). The susceptibility of the rats to immunocytoma was under genetic control; e.g., LOU/C/Wsl rats had a dominant locus (or loci) of susceptibility that could induce immunocytoma in inbred AUG/Wsl or inbred A X C9935/Wsl rats. However, inbred Okamoto/Wsl rats had at least one dominant locus of resistance that did not exist in LOU/C/Wsl, LOU/M/Wsl, AUG/Wsl, or A X C9935/Wsl rats.


Inhibition of 1,2-dimethylhydrazine-induced neoplasia of the large intestine in female CF1 mice by carbon disulfide. Disulfiram, diethyldithiocarbamate, and bis-(ethylxanthogen) inhibit symmetrical 1,2-dimethylhydrazine dihydrochloride (DMH)-induced neoplasia of the large bowel in female CF1 mice. These three compounds contain a carbon disulfide (CS2) moiety in their structure. In the present study, CS2 itself was found to inhibit DMH-induced neoplasia of the large bowel in female CF1 mice. Thus a relatively simple compound is now available for investigation of the mechanism of inhibition of DMH-induced neoplasia by a group of sulfur-containing inhibitors having common structural features.


Amoebic liver abscess in Wessex--a retrospective survey of 24 cases. The clinical features and response to treatment of 24 patients with amoebic liver abscess in Wessex are presented. Two patients died before adequate treatment could be instituted, but 6 of the remaining 22 patients (27%) did not respond to single courses of conventional anti-amoebic therapy. Possible reasons for this high failure rate are discussed. It is concluded that although Metronidazole is a highly effective anti-amoebicide, there remains a place for other drugs such as Emetine. The importance of early diagnosis of Amoebic Liver Abscess is emphasised.


Hazards of cortisone therapy in hepatic amoebiasis. Twelve cases were presented as amoebic liver abscess. They were clinically diagnosed and confirmed by screening, selective hepatic angiography and aspiration of abscess cavity. History of cortisone therapy was obtained in 66 per cent of the cases within a period of 1--3 months. Corticosteroids being immunosuppressive drugs may turn dormant amoebic hepatitis into liver abscess.


The value of mediastinoscopy--experience of 374 cases. The diagnostic value of 374 mediastinoscopies with biopsies from 1958-1971 is shown. The procedure has been evaluated earlier. The observation period in this report is so long that the clinical diagnoses are very reliable and give the material special interest. Over 90 per cent of sarcoidosis cases were diagnosed. The procedure is also shown to be of great value in investigating doubtful radiographic changes in the lungs and mediastinum. Mediastinoscopy showed tumor invasion of the mediastinal lymph glands in 79 of 216 patients with lung cancer so that 79 patients were spared thoracotomy. Mediastinoscopy can also be used to assess tumor spread in the planning of radiotherapy. In order to carry out a satisfactory lung diagnosis it is necessary to use mediastinoscopy.


Spontaneous perilymphatic fistula.

Spontaneous perilymphatic fistula. Sudden hearing loss from spontaneous perilymphatic fistula in a child managed by prompt surgical intervention and with recovery of hearing has not previously been reported. The historical and contemporary theories of fistula formation are reviewed. A child with spontaneous oval window rupture associated with a congenital malformation of the stapes and cochlear aqueduct is described together with his complete recovery of hearing following surgical repair. Some rationales explaining the mechanism of oval window rupture in this patient are suggested.


[Recurrent meningitis and cerebrospinal fluid fistula across the footplate of the stapes]. The clinical observation of a patient who presented an association of recurrent meningitis, unilateral deafness, and congenital anomaly of the ear is presented. The surgical exploration permitted us to find a CSF leak through the footplate of the stapes. The present concepts concerning especially the diagnosis and treatment of this pathology are discussed.


Sound localization: value in localizing lesions of the auditory pathway. Reports in the literature suggest that patients with otosclerosis, neural lesions such as acoustic neuroma, pontine lesions, and temporal lobe lesions may show abnormal sound localization ability. In the present experiment, 15 normal subjects and 22 patients with various auditory pathway lesions had sound localization testing using special apparatus. The results confirmed that patients with otosclerosis were unable to localize low frequency sounds. Those with temporal lobe lesions made judgments not significantly different from normal subjects. Patients with unilateral sensorineural deafness made errors localizing high frequency sounds. Those with acoustic neuromas made greater errors than those without, but the difference between these two groups just failed to reach statistical significance. The number of cases was however small, and further studies are in progress to attempt to define numerical criteria to assist clinical decisions with regard to the selection of patients for invasive investigations such as oil cisternogram.


The effects of indomethacin on inner ear fluids and morphology. Metabolic disturbances may affect inner ear fluid homeostasis in various ways. The membrane sodium-potassium pump must play a role in this homeostasis, and as this pump derives energy from A.T.P. it may also depend somewhat on the presence of prostaglandins, through their stimulatory effect on the adenylate cyclase system. Salicylates suppress prostaglandins; and Indomethacin is even more potent in this respect. Could the temporary ototoxic effects of salicylates and Indomethacin be due to prostaglandin suppression? Further, could energy system problems involving prostaglandins be related to the development of endolymphatic hydrops? These questions prompted this study. Sublethal doses of Indomethacin were given to 14 guinea pigs in order to maximally suppress prostaglandins. Samples of perilymph and endolymph were analyzed for sodium and potassium concentrations and compared to normal controls. No significant differences were found in either acute (two to 24 hour) or chronic (three week) experiments. Light microscopic examination of serially sectioned cochleae in similarly treated animals showed, in a few cases, somewhat questionable distension of Reissner's membrane. Electron microscopy or the organ of Corti did not demonstrate any abnormalities. The study suggests that Indomethacin does not produce significant inner ear electrolyte shifts or endolymphatic distension, at least over the short term.


Heterotopic salivary pleomorphic adenoma. The occurrence of heterotopic salivary tissue in the head and neck is briefly reviewed, and an additional case of heterotopic cervical pleomorphic adenoma added to the literature.


Primary pleomorphic liposarcoma of the larynx. Liposarcoma is a rare tumor in the larynx. A case of such lesion occurring in a 52 year old male patient is described. This is the second case to be reported in the world literature. The patient underwent hemilaryngectomy and later total laryngectomy for a recurrent tumor and is living and well six years after diagnosis.


Carcinoma of the lip--a case presentation. An unusually advanced case of squamous cell carcinoma of the lip is presented. Case management involved the use of a radiosensitizing agent, radiotherapy, surgical resection, and reconstruction. Two years later the patient is free of disease.


Open reduction of nasal fractures.

Open reduction of nasal fractures. Open reduction of nasal fractures has been defined and discussed from a clinical standpoint. Specific advantages of the procedure are mentioned with the suggestion that perhaps more of these procedures should be performed. Reference is made to the authors' series of 788 cases, with analysis of type of injury, age group, and procedure performed.


Altered E2 glycoprotein of Sindbis virus and its use in complementation studies. We have detected a Sindbis virus variant that contains a smaller-molecular-weight form of the viral glycoprotein E2. The molecular weight of the PE2 precursor and the glycosylation pattern of the smaller E2 are normal, thus indicating that this E2 is formed by an aberrant proteolytic cleavage. The altered E2 was detected in an RNA+ temperature-sensitive mutant that was defective in proteolytic cleavage, but the abnormal PE2-to-E2 reaction could be separated from the ts mutation and is not itself a temperature-sensitive defect. We used the variant E2 as a marker to monitor the complementation reaction between an RNA+ and an RNA- mutant and discovered that complementation was not reciprocal; the RNA defect was corrected by the RNA+ mutant gene products but the RNA+ defect was not complemented by any RNA- gene products. Other studies have shown that the smaller E2 is not preferentially selected during viral maturation and budding. No significant changes have been detected in the biological activity of virions with this altered E2 protein. Comparison of the electrophoretic migration of the E1 and E2 Sindbis viral glycoproteins in a two-dimensional polyacrylamide slab gel system that was first run in the absence of sulfhydryl-reducing reagent and then with beta-mercaptoethanol indicated that the mobility of E1, but not that of E2, was significantly altered by reduction.


Stoichiometry and specificity of binding of Rauscher oncovirus 10,000-dalton (p10) structural protein to nucleic acids. A structural protein of Rauscher oncovirus of about 8,000 to 10,000 daltons (p10), encoded by the gag gene, has been purified in high yield to apparent homogeneity by a simple three-step procedure. The purified protein was highly basic, with an isoelectric point of more than 9.0, and its immunological antigenicity was chiefly group specific. A distinctive property of the protein was the binding to nucleic acids. The stoichiometry of p10 binding to Rauscher virus RNA was analyzed using both 125I-labeled p10 and 3H-labeled RNA. The protein-RNA complex, cross-linked by formaldehyde, was separated from free RNA and free protein by velocity sedimentation and density gradient centrifugation. A maximum of about 140 mol of p10 was bound per mol of 35S RNA, or about one molecule of p10 per 70 nucleotides. This protein-RNA complex banded at a density of about 1.55 g/ml. The number of nucleic acid sites bound and the affinity of p10 binding differed significantly among the other polynucleotides tested. The protein bound to both RNA and DNA with a preference for single-stranded molecules. Rauscher virus RNA and single-stranded phage fd DNA contained the highest number of binding sites. Binding to fd DNA was saturated with about 30 mol of p10 per mol of fd DNA, an average of about one p10 molecule per 180 nucleotides. The apparent binding constant was 7.3 X 10(7) M(-1). The properties of the p10 place it in a category with other nucleic acid binding proteins that achieve a greater binding density on single-stranded than on double-stranded molecules and appear to act by facilitating changes in polynucleotide conformation.


Synthesis of defective viral DNA in HeLa cells infected with adenovirus type 3. Virus-specific DNA fragments that are shorter than the full-length viral genomes have been isolated from HeLa cells productively infected with adenovirus type 3. A number of predominant size classes could be detected by gel electrophoresis and hybridization, and the array of sizes was similar or identical to the selection in DNA purified from incomplete particles of this serotype (E. Daniell, J. Virol. 19:685-708, 1976). A large fraction of these short DNA molecules contained long inverted terminal repetitions, as did DNA molecules from incomplete particles. Restriction analysis showed that these subgenomic molecules consist of sequences from the two molecular ends of the normal genome. These results suggest that the predominance of left-hand end fragments seen in packaged incomplete DNAs results from selective packaging, whereas the predominance of certain size classes of intracellular viral DNA is a function of prepackaging events. The incomplete DNAs were generated at all times during viral DNA replication, and the yield relative to complete DNA did not seem to vary significantly with time or multiplicity of infection or when the virus was propagated on different human cell types.