Ataxia telangiectasia with hepatocellular carcinoma in a 15-year-old girl and studies of her kindred.

We studied a case of familial ataxia-telangiectasia in a 15-year-old girl who had a clinical history of cerebellar ataxia and recurrent pulmonary infections. She was found at autopsy to have a hepatocellular carcinoma, which has been described twice previously in the literature as occurring with this disorder. Family studies on the majority of her seven siblings (the product of one father and two mothers who were identical twins) showed one brother to have classic features of cerebellar ataxia, IgA deficiency, markedly elevated alpha-fetoprotein levels, and characteristic chromosomal abnormalities. This boy also died later of hepatocellular carcinoma in 1984. An affected sister had previously died of a respiratory tract infection.

Early diagnosis by liver scan of a right-sided traumatic diaphragmatic hernia.

A case of right-sided diaphragmatic rupture from blunt trauma in a 37-year-old man is described. Diagnosis was established by a liver scan obtained in the acute stage of injury. Primary repair was followed by uneventful recovery. Attention is called to this test for its potential in evaluating the integrity of the right diaphragm.

Phosphate fluxes in single muscle fibres of the spider crab, Maia squinado.

1. The rates of influx and efflux of [32P]orthophosphate (Pi) have bben measured in single muscle fibres of the spider crab, Maia squinado. 2. Rates of influx of 32Pi from salines containing 0 . 11 to 0 . 37 mM-Pi ranged from 0 . 11 to 0 . 41 p-mole cm-2 sec-1. 3. After injection of [32P]orthophosphate there was an early rapid phase of 32P efflux which was maximal after about 5-10 min, then a gradual decline until a low steady-state efflux rate was established after about 100 min. The rate of decline of 32P efflux was similar to the rate of equilibration of injected 32Pi with arginine phosphate and ATP. 4. The steady-state rate of 32P efflux was typically about 0 . 70 p-mole cm-2 sec-1 when the sarcoplasmic Pi concentraion was 5 m-mole kg-1. Exposure of mucle fibres to conditions which caused contraction and increased the sarcoplasmic concentration of Pi also increased the rate of 32P efflux, which appeared to be linearly related to sarcoplasmic Pi concentration. 5. The results are compared with previous measurements of phosphate fluxes in nerve.

The effect of ouabain on amino acid and orthophosphate influxes in squid giant axons.

1. Some effects of ouabain on the uptake of 14C-labelled amino acids and 32P-labelled orthophosphate into squid axons have been investigated. 2. Ouabain in artificial sea water reduced the uptake of glycine, L-alanine, L-arginine, L-aspartate and L-glutamate. After a period of 3 hr in ouabain the inhibition of glycine and L-glutamate uptake was appreciable. 3. After 3 hr in ouabain the axoplasmic Na concentration had increased by only about 14% and the K concentration had fallen by only about 9%. It therefore seems unlikely that changes in the Na and K gradients across the membrane due to ouabain are the reason for the inhibition of amino acid uptake. This was confirmed when the axons were made to conduct impulses at 200/sec for 40 min. There was no subsequent inhibition of glycine and L-glutamate uptake, even though the axoplasmic Na increased by about 42% and the K decreased by about 37%. 4. A detailed investigation of the time course of the inhibition of amino acid uptake by ouabain in which intracellular scintillator techniques were used, showed that there was no inhibition for 30--100 min, and then it occurred fairly quickly. This course of events was not affected by the protein synthesis inhibitor cycloheximide. It is unlikely that the inhibition of orthophosphate uptake is subject to a similar delay since this had reached a maximum after 40 min. 5. It is concluded that the inhibitory effects of ouabain on amino acid uptake in squid axons are not due to effects on the Na and K gradients brought about by inhibition of the Na-K pump. The delay in the inhibiton may reflect the operation of an intracellular regulatory mechanis, which is initiated when ouabain inhibits the pump but which takes time to operate. If the formation of an inhibitory second messenger molecule is involved this is unlikely to be a protein.

Glycine fluxes in squid giant axons.

1. The influx of a number of amino acids into squid giant axons has been studied. Particular emphasis has been placed on glycine and to a lesser extent glutamate. 2. To facilitate the study of the uptake of 14C-labelled amino acids a technique was devised in which the 14C taken up was measured directly in the intact axon with a glass scintillator fibre. This technique gave results similar to the usual technique in which the axoplasm was extruded for the assay of radioactivity. 3. The changes in glycine influx with extracellular glycine concentration suggests that two saturating components are present, one with high affinity and one with low affinity. 4. The glycine influx does not seem normally to be sensitive to the removal of extracellular sodium by replacement with choline. A Na-sensitive component appeared, however, after a period of immersion in artificial sea water. There was also some depression of glycine influx if Na were replaced by Li. 5. Glutamate uptake was greatly reduced by removal of extracellular Na in confirmation of work by Baker & Potashner (1973). Orthophosphate uptake was also greatly reduced by removal of extracellular Na. 6. CN reversibly inhibited glycine uptake after a delay, indicating that part of the uptake mechanism may require ATP. 7. 14C-labelled glycine injected into squid axons was found not to exchange to any serious extent with other compounds over periods of a few hours. The glycine efflux could therefore be studied. This was found to be markedly increased by extracellular glycine and by certain other neutral amino acids applied extracellularly in the artificial sea water. 8. The enhanced glycine efflux in extracellular glycine was not affected by ouabain and CN. 9. It is suggested that glycine uptake in squid axons involves two components. One is sensitive to CN and ouabain and probably derives energy from ATP break-down. The other is probably an ATP independent exchange diffusion system in which other amino acids as well as glycine can exchange for glycine. Both these systems are independent of extracellular Na concentration. A third Na-dependent system may appear under certain conditions.

The turnover of phosphorus compounds in crab muscle fibres.

1. The exchange of 32P injected into single crab muscle fibres as either orthophosphate or ATP has been studied. The results have been analysed in terms of a simple kinetic model. 2. The exchange of 32P between ATP and arginine phosphate is considerably faster than that between ATP and orthophosphate during rest and during contraction in caffeine. 3. The rate constants obtained at rest after the injection of either orthophosphate or ATP labelled with 32P were of the same order. They were also of the same order as those which have been obtained previously for squid axons. 4. The exchange during caffeine contraction of 32P unjected as orthophosphate gave rate constants which were consistent with an increased rate of splitting of ATP and with the rate constants needed to account for the observed net formation of orthophosphate. The results obtained after the injection of 32P-labelled ATP during caffeine contraction were less clear cut.

The efflux of calcium from single crab and barnacle muscle fibres.

1. The efflux of calcium, as the isotope (45)Ca, has been investigated from single muscle fibres from the barnacle Balanus nubilus and from the crab Maia squinado.2. If the isotope was initially injected with sufficient calcium (5-65 mM) to cause a contraction, the efflux did not follow first order kinetics. There was an early rapid phase which reached a peak after 5-10 min and then declined slowly over a period of 50-150 min to a low residual value.3. Injection of the isotope with the calcium-binding agent EGTA, so that the injected free calcium concentration was ca. 2 x 10(-8)M, abolished the initial rapid loss of calcium. The efflux rose to give a steady value after 10-15 min and its magnitude was similar to the value of the residual efflux.4. The rate constant for the low residual loss was ca. 7 x 10(-4) min(-1) for Maia and ca. 17 x 10(-4) min(-1) for Balanus. The rate constant predicted a calcium efflux of 0.4 p-mole/cm(2).sec for Maia and 1-2 p-mole/cm(2).sec for Balanus at 16-25 degrees C based on the total fibre calcium concentration.5. The residual calcium efflux was not affected by 0.5 mM ouabain or 0 potassium salines applied externally. It was stimulated, some 10-15 times in Maia and to a lesser extent in Balanus, by salines containing 600 mM potassium or 2-5 mM caffeine. The increased efflux was associated with a brisk contraction.6. External application of salines containing 20, 40 or 60 mM potassium or 0.5 mM caffeine in Maia produced some stimulation of the residual efflux but no visible contraction.7. Pre-treatment of Maia fibres with 40 mM potassium or 0.5 mM caffeine salines abolished the ability of the fibres to respond to higher concentrations of these agents. A depletion of a releasable calcium fraction by these subthreshold stimuli could explain this phenomenon.8. Electrical stimulation, the injection of 50 mM calcium chloride or 50 mM caffeine produced an elevated calcium efflux which was associated with a contraction.9. Intracellular injections of EGTA only lowered the residual efflux by up to half its initial value. This suggests that calcium can be released rapidly within these muscle fibres and that the sarcoplasmic calcium concentration is not much altered from its normal value by the injection.10. The experiments suggest that in Maia, changes in the calcium efflux reflect in magnitude, but not in time course, the internal calcium changes which can be observed with the calcium-sensitive protein, aequorin.

The resting membrane potential of the somatic muscle cells of Ascaris lumbricoides.

1. The resting membrane potential of Ascaris muscle fibres, which is normally relatively insensitive to ion changes in the medium, has been measured under a wide variety of conditions.2. The results have been interpreted in terms of a form of the constant field equation containing additional terms for the contribution of ions and charged groups other than potassium, sodium and chloride.3. Normally the contribution of the additional terms is large and tends to outweigh the contributions of potassium, sodium and chloride.4. The contribution of the additional terms is considerably reduced in the absence of sodium and in the presence of gamma-amino butyric acid and acetylcholine.5. It is suggested that the additional terms may represent the contribution of an electrogenic active transport mechanism to the factors determining the membrane potential.

The influx of orthophosphate into squid giant axons.

1. The influx of (32)P, applied externally as orthophosphate, into the axoplasm of squid giant axons has been studied.2. An average orthophosphate influx of 20.9 f-mole/cm(2).sec is obtained if the (32)P found in the axoplasm is assumed to be indicative of orthophosphate which has crossed the axolemma.3. The influx does not show very much dependence on external orthophosphate concentration in the range 0.02-0.5 mM.4. The influx is reduced by cyanide, 2,4-dinitrophenol, ouabain and by the absence of external potassium.5. The (32)P appears to arrive in the axoplasm as orthophosphate.6. It is concluded that there is an inward movement of orthophosphate into the axons which is mediated by an active transport process and that this may have some connexion with the active transport of sodium and potassium.