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Biomedical subjects

R C Thomas

Publications and source records attributed to R C Thomas.

At least 73 records · Page 4Linked to original sources
PubMed1985

Spectinomycin modification. II. Spectinomycin C-3'-modification via diazoketone intermediates.

The C-3'-carbonyl group of N-protected spectinomycin is efficiently converted into a diazo group via base treatment of the corresponding tosylhydrazone. The diazo group imparts a new synthetically useful reactivity pattern on the sugar ring of the molecule. The synthesis of C-3'-deoxo-, monohalo- and dihalospectinomycins via the intermediacy of these diazo compounds is described. The reduced bioactivity of these analogs as compared to the parent and the C-3'-dihydro and aminospectinomycins established the need for hydrogen bonding groups in this region of the molecule for good activity, further refining the structure activity relationships in the spectinomycin series.

Chemical Phenomena↗
PubMed1985

Spectinomycin modification. III. Spectinomycin analogs with C-3'-branched chain sugars.

A variety of C-3'-branched chain analogs of spectinomycin has been synthesized via the intermediacy of spectinomycin derived diazoketones. In vitro antibacterial assay of these compounds has underscored the importance of hydrogen bonding functional groups in this region of the molecule. The most potent of these analogs had activity greater than or equal to the parent.

Carbohydrates↗
PubMed1984

Acid influx into snail neurones caused by reversal of the normal pHi-regulating system.

Intracellular pH (pHi), and Na+ and Cl- activities were measured with ion-sensitive micro-electrodes in Helix aspersa neurones, and the effects of reducing external pH (pHo) were investigated. When pHo was changed from 7.5 to 6.5 keeping CO2 constant, there was a slow fall in pHi, a rise in internal Cl and a fall in internal Na. These ionic changes are opposite to those caused by normal operation of the pHi-regulating system. These effects of external acidification were inhibited by the application of SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid) or by the removal of external Cl. Raising intracellular Na activity by inhibiting the Na pump increased the rate of fall of pHi in acid solutions. In acid solutions the average rate of acid uptake attributable to reversed pHi-regulation was about three times the rate of loss of internal Na, and about twice the rate of Cl uptake. We conclude that these intracellular ion changes in acid solutions were largely due to a reversal of the pHi-regulating mechanism, so that it carried acid into, rather than out of, the cell interior.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1984

The effect of leakage on micro-electrode measurements of intracellular sodium activity in crab muscle fibres.

The effect of lowering extracellular Na (Nao) on the intracellular Na activity has been measured in single muscle fibres from the crab Carcinus maenas using Na+-sensitive glass micro-electrodes. Measurements have been made with recessed-tip micro-electrodes inserted radially into intact fibres, and with axial electrodes in cannulated fibres. Reducing Nao to one-tenth normal caused local contractions in intact fibres. The apparent steady-state internal Na (Nai) and the fall in Nai when Nao was reduced were found to vary considerably not only between different fibres but also when measured with different electrodes in the same fibre. The steady-state Nai, and the extent and rate of its decrease when Nao was reduced, could be reduced by pushing the Na+-sensitive electrode deeper into the fibre. Cannulated fibres generally had higher internal Na activities than intact fibres, but at comparable levels of Nai the rate of fall recorded from cannulated fibres when Nao was reduced was much slower than with intact fibres. In both intact and cannulated fibres the decrease in Nai was reduced by ouabain. The level of Nai recorded in cannulated fibres was sensitive to depolarization. Depolarizations from -50 to -30 mV resulted in a rise in Nai while further depolarization to 0 mV resulted in a fall in Nai. We conclude that both our results and those of Vaughan-Jones (1977) on undissected fibres are contaminated by leakage into the fibre round the micro-electrode. The true internal Na activity is probably much lower than previously reported.

Animals↗
PubMed1982

Hydrogen ion currents and intracellular pH in depolarized voltage-clamped snail neurones.

Until now the only reported effect of depolarization on the intracellular pH (pHi) of excitable cells in an acidification of the cell cytoplasm. It seems unlikely that this could be a direct effect of membrane potential because pHi is known to be regulated by an electroneutral mechanism and in most cells H+ ions are not in equilibrium with the membrane potential (Em). In any case the membrane conductance to H+ ions would be expected to be small because they are at such low concentrations on either side of the cell membrane. But it is possible that the H+ ion permeability of the membrane increases on depolarization just like that of other ions in the bathing medium depolarization just like that of other ions in the bathing medium (Na+, K+ and Ca2+ for example). To test this idea we have made pHi measurements on molluscan neurones under voltage-clamp. Our findings, presented here, provide evidence for a large increase in H+ ion permeability in depolarized cells. We suggest that this increase in proton conductance may be the basis for the "nonspecific' currents previously described in perfused molluscan neurones and we assess the physiological significance of this newly discovered pathway.

Animals↗
PubMed1982

Albocycline: structure determination by x-ray crystallography.

The structure and absolute configuration of the macrolide antibiotic albocycline (1a) has been determined by X-ray crystallographic analysis on the derived p-bromobenzoate (1b). The absolute configuration of albocycline is 4R, 7S, 12S, 13R.

Anti-Bacterial Agents↗
PubMed1981

A liquid ion-exchanger alternative to KCl for filling intracellular reference microelectrodes.

We have developed a filling solution for silanised microelectrodes consisting of potassium tetrakis (p-chlorophenyl) borate in octanol. Microelectrodes filled with this reference liquid ion-exchanger (RLIE) have equal selectivities to Na and K, and give the same membrane potential as do KCl-filled microelectrodes. The RLIE microelectrodes are more stable, less damaging to the cell membrane and do not leak Cl- ions. Their high resistance, however, makes them unsuitable for recording rapid potential changes or for passing current.

Animals↗
PubMed1981

The effects of chloride substitution on intracellular pH in crab muscle.

1. Intracellular pH (pHi) was measured in crab muscle fibres using pH-sensitive micro-electrodes. The mean stable pHi was 7.19 +/- 00.2 (S.E. of mean) and the corresponding mean membrane potential was -64.6 +/- 0.4 mV (S.E. of mean) at an external pH of 7.5. 2. The effects on pHi of replacing 20% (100 mM) of the external NaCl by the Na salts of various anions were examined. The anions of weak acid (pK'a greater than 4.5) caused large internal acidifications. The anions of strong acids (pK'a less than 2.6) caused little or no change in pHi. The anions of acids with an intermediate pK'a had varied effects on pHi. In particular salicylate (pK'a = 2.97) was found to cause a large fall in pHi. 3. Increasing the external pH reduced the effects of the anions of weak acids on pHi. It is argued that these effects are the result of the entry and subsequent dissociation of undissociated acid molecules. 4. The results with propionate were quantified by comparing them with the effects of 5% CO2 and were found to be smaller than expected. It is suggested that this is the result of substantial membrane permeability to the propionate anion.

Animals↗
PubMed1980

Effect of measured calcium chloride injections on the membrane potential and internal pH of snail neurones.

1. Ion-sensitive micro-electrodes were used to measure changes in intracellular pH (pHi) and internal chloride which resulted from the pressure injection of calcium chloride into identified Helix aspersa neurones. The internal chloride measurement allowed the quantity of calcium chloride injected to be estimated. 2. Application of the metabolic inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCmP) to a calcium-loaded cell caused an increase in the membrane potential comparable to the effect of injecting calcium itself. The effect was not observed in normal cells. 3. When injected in the presence of CCmp, calcium caused a much larger and longer-lasting effect on the membrane potential than that observed in untreated cells. 4. The injection of ruthenium red can increase and/or prolong the hyperpolarization caused by a given quantity of injected calcium. The pHi changes following calcium injection were biphasic and slower than normal. 5. In seven experiments, both hydrogen chloride and calcium chloride were injected into the same cell. The relative changes in pHi corresponded to the production of one hydrogen ion for each calcium ion injected. 6. The relationship between the quantity of calcium injected and the size of the induced hyperpolarization suggested that at least three calcium ions acting cooperatively are required to activate a potassium 'channel'. 7. Injection of barium chloride hyperpolarized the membrane after a delay of about 1 min. After several injections of barium the cell lost this response while retaining its normal response to calcium injection. Injection of barium also caused a slowly developing (biphasic) fall in pHi. 8. We conclude that injected calcium is normally rapidly taken up by mitochondria in exchange for hydrogen ions. If this uptake process is blocked by ruthenium red or CCmP, the calcium is taken up by a second, slower, process which also releases hydrogen ions. When pre-loaded, but not otherwise, the mitochondria will release calcium ions on treatment with CCmP. Injection of barium does not directly affect the membrane conductance, but causes the release of calcium from intracellular binding sites.

Animals↗
PubMed1978

Preparation of [14C]colestipol hydrochloride and its disposition in the human, dog and rat.

Colestipol hydrochloride, a polymeric, ion-exchange type, hypocholesterolemic agent, acting by sequestering bile acids, was labeled with carbon-14. The disposition of the labeled material was studied in the human, dog and rat. The extent of absorption from the gastrointestinal tract, as judged by urinary excretion of radioactivity, was very small and correlated well with the contents of water-soluble and dialyzable materials in the colestipol hydrochloride. Results were consistent with the dialyzable material in the drug being the absorbable species.

Animals↗