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Biomedical subjects

J Diamond

Publications and source records attributed to J Diamond.

At least 199 records · Page 11Linked to original sources
PubMed1978

Antimotility and antisecretory activity of some aryl substituted amidinoureas.

A number of aryl substituted amidinoureas have been prepared and examined for their gastrointestinal spasmolytic, antimotility, antidiarrheal and antisecretory effects. In general, antisecretory and antimotility effects have been found to be associated with each other in these compounds. The structure-activity relationships found show that substitution of the aromatic ring in positions other than 2 and 6 correlates poorly with potency, and potency of such compounds is low. In contrast to this, 2,6-disubstitution confers high potency. The potency of 2,6-disubstituted compounds declines sharply with increasing weight of substitution of the amidinourea chain, with the important exception of the N-alkoxyamidinoureas. Increasing the molecular weight of an N-alkoxy substituent has a much less profound effect than the corresponding increase has in an N-alkyl substituent. High potency in an amidinourea may well be related to low basicity (or a high pKa value for its conjugate salt) but there is insufficient data to support this hypothesis fully. The actual tautomeric structure of an amidinourea probably affects its potency and this is discussed briefly.

Amidines↗
PubMed1977

Neuronal transport in salamander nerves and its blockade by colchicine.

Neuronal transport and the effects of colchicine on it has been studied in salamander spinal nerves. Cholinesterase (ChE) accumulation above the cut region of a nerve at 12.5 degrees C was shown to depend upon two processes. One caused a transient increase which declined to zero by 24 h; the other was explained by axoplasmic transport. At 22 degrees C the transient change was not observed, but the rate of accumulation attributable to transport increased. The Q10 for this transport over the range 12.5 degrees C--22 degrees C is approximately three. The ChE accumulation in the sensory component of the mixed nerve was about equal to that in the motor. The rate of fast axoplasmic transport of labeled leucine was 56 mm/day at 22 degrees C; if ChE moves at the same rate, then only 7% of the total enzyme is carried by fast axoplasmic transport. The transport of ChE was reduced by at least 50% when nerves were bathed in a 75 mM solution of colchicine for 30 min; this treatment is known not to cause subsequent degeneration of these nerves. The rate of slow flow of labeled material after bathing the nerve trunk in tritiated colchicine was found to be approximately 0.5 mm/day.

Animals↗
PubMed1977

Conjugated polyene fatty acids on fluorescent probes: spectroscopic characterization.

This paper is the first in a series which extends introductory studies of parinaric acid and its phospholipid derivatives as membrane probes (Sklar, L.A., Hudson, B., and Simoni, R.D. (1975), Proc. Natl. Acad. Sci. after U.S.A. 72, 1649; (1976), J. Supramol. Struct. 4, 449). Parinaric acid has a conjugated tetraene chromophore and exhibits many spectroscopic properties common to linear polyenes. Its absorption spectrum is characterized by a strong near-ultraviolet transition with vibronic structure, which is strongly affected by solvent polarizability. The fluorescence emission occurs at considerably lower energy than the absorption and the wavelength of the emission is nearly independent of the solvent. The fluorescence quantum yield and lifetime are strongly affected by temperature and solvent. These spectral features are interpreted in terms of an excited electronic-state order such that a weak transition occurs at longer wavelengths than the strongly allowed transition which dominates the absorption. The sensitivity of the fluorescence quantum yield an lifetime to environment is shown to be due primarily to variations in the nonradiative rate, although changes in the radiative rate constant are also observed and interpreted. The absorption spectrum (epsilon max greater than 65 000) is in the 300-320-nm range, a region relatively free of absorption due to intrinsic biological chromophores. Shifts of several nanometers are characteristic of different environments. These shifts are compared to similar effects observed for a series of diphenylpolyenes for which new data are given and are correlated using a simple but adequate theory of solvent shifts. The intrinsic (or radiative) fluorescence lifetime is near 100 ns in a wide variety of environments. This is much longer than the intrinsic lifetime calculated from the absorption spectrum and strongly supports the proposed excited-state order.

Fatty Acids, Unsaturated↗
PubMed1977

A quantitative study of the mechanosensory innervation of the salmander skin.

We have investigated by physiological means the characteristics and organization of the mechanoreceptors in the skin of the salamander hind limb. A controlled mechanical stimulator with a tip diameter of a few microns was used to activate single mechanoreceptors, and afferent impulses were recorded from whole spinal nerves. 2. The mechanoreceptors of the skin are rapidly adapting. When random spots on the skin were tested, the stimulus strength needed to evoke an impulse varied from one location to another. The histogram of percentage occurrence of these critical stimuli in a given skin has the same form whether the sampled spots are 50 mum apart and are all included in a small area, or whether the spots are sampled as much as 1 mm apart across the entire limb. The histogram is skewed, with the highest-percentage occurrence in the low-threshold range. 3. One interpretation of the findings is that there is a single population of mechanoreceptors, of uniform threshold, spaced far enough apart for a stimulator of small diameter to be situated between them. By locating a low-threshold spot, and then determining the increase in stimulus required to excite it at a known distance away, it was possible to estimate the relationship between the strength of the stimulus and the receptive field size of such a population of receptors; we were then able to infer the average receptor spacing and receptive field size. The values are approximately 250 and 75 mum respectively. 4. From appropriate maps of detailed systematic surveys of the skin sensitivity to touch it was possible to define discrete low-threshold areas. These areas had approximate radii in the range 50-75 mum, and their centres were about 200-250 mum apart; these values are consistant with those predicted above. We conclude that the experimentally determined sensitive areas represent the receptive fields (at threshold) of individual mechanosensory endings. There are approximately twenty to thirty of them per square millimetre. 5. Receptive fields of single mechanosensory axons (i.e. of sensory 'units') were measured by an occlusion technique using two prodders. These fields vary from 0-05 to 2-5 mm2, and are generally organized as discrete areas with only a little overlap among them. Individual axons supply from five to seventy-five mechanoreceptors. 6. The findings provide a basis for quantitative studies of plasticity involving the mechanosensory system of the salamander skin.

Action Potentials↗
PubMed1977

The effects of nerve section and of colchicine treatment on the density of mechanosensory nerve endings in salamander skin.

We have shown that when one of the spinal nerves supplying the salamander hind limb is cut or treated with colchicine, the fields of the remaining nerves enlarge in area; whereas nerve section produces Wallerian degeneration, the colchicine-treated nerves conducted action potentials normally and their peripheral fields remained unchanged in area (Aguilar, Bisby, Cooper & Diamond, 1973). Since colchicine-treatment reduced neuronal transport, and nerve-section eliminated it, we proposed that nerve sprouting is regulated by factors normally conveyed to the endings by axoplasmic transport. 1. We have now investigated the effects of colchicine on the thresholds and distribution of individual mechanosensory endings in the skin. If reduction of neuronal transport were enough to cause the threshold to be increased to the point of total unresponsiveness, then this could be a sign of an early stage of degernation in those terminals. It could then be hypothesized that products of degeneration were providing a stimulus for adjacent nerves to sprout. 2. Quantitative physiological studies of the effects of colchicine doses known to interfere with fast axoplasmic transport, indicate that in some experiments the terminal field of the treated nerve was invaded by sprouting fibres from neighbouring axons, when its own endings were unchanged in number, distribution and sensory thresholds. In other experiments the colchicine-treated nerve endings showed an increase in threshold but their function was otherwise unchanged; a similar adjacent nerve sprouting occurred. In a final group, colchicine caused total unresponsiveness of some endings of the treated nerve. 3. When a region of skin was partially denervated by nerve section, the physiological analysis indicated that the number of new mechanosensory endings which sprouted from the remaining axons exactly matched the number lost by nerve degeneration: furthermore the distribution of the endings was normal. It therefore appears that sprouting ceased when the original density of mechanosensory endings in the skin was restored. 4. The possibility that the drug induced sprouting as a consequense of a direct action on the skin is unlikely. With [3H]colchicine, we found that the accumulation of label in the skin of the untreated limb, in which sprouting did not occur, equalled that of the opposite limb. 5. The present results lend support to the original hypothesis of Aguilar et al. (1973), which proposed that collateral sprouting of intact nerves occurs when the supply of neuronally transported factors becomes inadequate to balance out the effects of a postulated target-tissue stimulus. In the Discussion other examples of collateral nerve sprouting, such as that following adjacent denervation, are shown to be explainable by this hypothesis.

Action Potentials↗