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Biomedical subjects

M E Lewis

Publications and source records attributed to M E Lewis.

At least 127 records · Page 7Linked to original sources

Pacemaker-induced hypotension.

We report a case of hypotension and decreased cardiac output resulting from artificial ventricular pacemaker rhythm. Hemodynamic deterioration was associated with loss of normal time relationships between atrial and ventricular contraction and paradoxical fall in systemic vascular resistance despite a low output state. The therapeutic implications of this unusual response are discussed.

Aged↗

Reinnervation of the denervated striatum by substantia nigra transplants: functional consequences as revealed by pharmacological and sensorimotor testing.

Embryonic substantia nigra (SN) was transplanted to the neostriatum in adult rats subjected to a unilateral or serial bilateral destruction of the nigrostriatal dopamine (DA) pathway. The survival of the graft and the growth of DA-containing fibers from the graft into the host brain was studied by fluorescence histochemistry and micro-fluorometry. The motor asymmetry, and the contralateral 'sensory neglect' induced by a unilateral destruction of the nigrostriatal DA pathway, were monitored in the transplanted rats and in non-transplanted controls through repeated measurements of the amphetamine-and apomorphine-induced rotational behaviour, and through analysis of the rats performance in a number of sensorimotor tests. Finally, the development of aphagia and adipsia after a serial bilateral destruction of both nigrostriatal DA pathways were followed in rats bearing bilateral SN transplants and in lesioned non-transplanted controls. The results show that large parts of the dorsal neostriatum can be reinnervated by DA-containing axons from the intracortical transplant and that this new DA input can fully compensate for the amphetamine-induced motor assymmetry that resulted from the initial destruction of the innate nigrostriatal DA pathway. The fluorescence microscopical observations provide strong evidence that the compensation of the amphetamine-induced rotational response was specifically related to the re-establishment of a new DA input to the denervated neostriatum, and that the degree of rotational compensation was well correlated to the magnitude of ingrowth into the neostriatum. Subsequent surgical removal of the SN transplant reinstated the initial rotational behaviour. In sharp contrast to the marked compensation in motor asymmetry, the transplanted rats showed no tendency to recover in their sensorimotor performance. Thus, while the sensorimotor deficit had recovered in the control group a marked contralateral 'sensory neglect' remained in the transplanted animals. Furthermore, removal of the transplant produced a significant improvement in their sensorimotor performance within 3 days. In the bilaterally transplanted animals the presence of the transplants did not prevent the development of severe adipsia, aphagia and akinesia following the destruction of the remaining contralateral nigrostriatal pathway. In fact, the recovery from the consummatory deficits tended to be better in the lesioned control rats than in the transplanted ones. It is concluded that SN transplants reinnervation the dorsal part of the neostriatum are able to replace the innate SN in normalizing some aspects of the rats motor behaviour, while their sensorimotor deficits and deficits in consummatory behaviour were unaffected. It is suggested that this dissociation of transplant-induced recovery is due to the failure of the SN transplants to reinnervate those parts of the neostriatum which are most directly implicated in sensorimotor and consummatory behaviour.

Animals↗

Renin-like effects of NGF evaluated using renin-angiotensin antagonists.

Intracranial injection of angiotensin II (AII) or activation of the cerebral isorenin-angiotensin system with intracranial renin causes an immediate thirst and a delayed sodium appetite in the rat. Nerve growth factor (NGF), a polypeptide trophic factor for peripheral sympathetic and sensory neurones, has also been reported to be a potent stimulus to thirst and sodium appetite when injected into the brain of the rat. Lewis et al. drew attention to the marked similarity between the effects of 2.5S NGF and renin on thirst and sodium appetite and suggested that the NGF responses were mediated by the cerebral isorenin-angiotensin system. We report here that NGF-induced thirst and sodium appetite, as well as increased blood pressure and increase ornithine decarboxylase activity in the brain and liver, depend on the formation of AII (see also ref. 6).

Angiotensin II↗

Herpes zoster mandibularis.

A case of Herpes zoster of the mandibular nerve in an 80 year old man is reported. Herpes zoster infection affecting only the mandibular branch of the trigeminal nerve is rare. It is proposed that the distribution of lesions is a consequence of a unique latent site of the virus within neurons of the gasserian ganglion innervating the mandibular division of the trigeminal nerve.

Aged↗

Induction of ornithine decarboxylase by renin-free nerve growth factor.

Renin-free nerve growth factor causes the induction of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) in superior cervical ganglia from neonatal rats but not in the brain of mature rats. Less pure preparations of nerve growth factor induce the enzyme in both brain and ganglia. The induction of ornithine decarboxylase in the central nervous system appears to be due to renin, not to nerve growth factor itself.

Angiotensin II↗

Nerve growth factor: effects on D-amphetamine-induced activity and brain monoamines.

Adult male rats were given 6-hydroxydopamine lesions of the nucleus accumbens, followed immediately by injections of saline or nerve growth factor (NGF; 125 B.U.) near the substantia nigra. Such lesions were previously reported to attenuate the locomotor response to D-amphetamine. NGF-treated rats showed an enhanced response to D-amphetamine (1.5 mg/kg) when tested 15 days postoperatively. Levels of dopamine and norepinephrine in the striatum and nucleus accumbens were equivalently depressed in the two lesion groups, indicating that the apparent recovery of the NGF-treated rats was probably not due to catecholaminergic neuronal regrowth. Intracerebral NGF administeration enhanced the response to D-amphetamine 15 days later in rats without lesions, and also appeared to result in increased turnover of brain norepinephrine and serotonin at 3, but not 15, days postadministration. NGF might increase dopamine turnover at 15 days, but the evidence obtained did not convincingly confirm or negate this possibility. The results in brain-damaged and intact rats, and also modify the apparent turnover of brain monoamines.

Animals↗

Short-latency drinking and increased Na appetite after intracerebral microinjections of NGF in rats.

NERVE GROWTH FACTOR (NGF) is a polypeptide trophic factor for peripheral sympathetic and sensory neurones(1,2). Apparent NGF(3-5) and NGF receptors(6,7) have also been identified in the brain, and intracerebral administration of NGF in the adult rat produces marked biochemical(8) and morphologica(9,10) changes in brain tissue. These findings, taken together with the observations that central injections of NGF facilitate behavioural recovery from brain damage(11,12), indicate that this polypeptide may have an important role in brain function. It has been observed that rats given intraventricular injections of up to 2.3 microg NGF drink copiously (M.E.L. and G. Guroff, unpublished observations). Perkins et al.(13) reported that diencephalic application of crystalline NGF (1-15 microg) resulted in an intense polydipsia. The present report confirms the observations of M.E.L. and Guroff, and extends the findings of Perkins et al.(13) by using solutions of NGF instead of crystals. It also describes for the first time a second phenomenon produced by intracranial administration of NGF, namely an intense appetite for aversive concentrations of sodium solutions.

Journal Article↗

Nerve growth factor increases activity of ornithine decarboxylase in rat brain.

Intraventricular administration of nanogram quantities of nerve growth factor to adult rats results in a marked increase in the activity of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) in the brain. The increase occurs in all major brain regions and the activity is maximal by 7.5 hr after administration. The enzyme response to nerve growth factor increases in magnitude during maturation; the relative increase in ornithine decarboxylase activity in adult animals is much greater than that in young. Neither insulin nor bovine growth hormone was able to increase ornithine decarboxylase activity to the same extent as did nerve growth factor. When brain was separated into neuronal- and glial-enriched fractions, induction of ornithine decarboxylase was found in both, but a greater increase was observed in the glial fraction.

Journal Article↗

Carnivoran paleoguilds of Africa: implications for hominid food procurement strategies.

Tool-using hominids, as carnivorous animals, would have been part of the various carnivore guilds present in Plio-Pleistocene Africa. Hominid dietary strategies must be understood within the larger context of carnivore behavior and ecology, as carnivorans could have affected the abilities of hominids to procure meat and/or marrow. The functional anatomy of extant and fossil carnivorans was examined to infer behaviors in fossil carnivorans that would have impacted on hominid dietary strategies in terms of carcass availability. Comparisons of guild structure were carried out to examine changes in carnivoran interactions and their implications for hominid behavior. Plio-Pleistocene carnivorans engaged in a wider range of behaviors than modern carnivorans. The sabertoothed felids Dinofelis and Megantereon probably did not provide much larger carcasses than modern species. Another sabertooth, Homotherium generated larger carcasses, but may have disarticulated and transported these carcasses. Fossil representatives of modern taxa may not have been equivalent ecologically within the carnivoran guild. Overall, hominids in eastern Africa probably had a greater range of scavenging opportunities than did those of southern Africa during the Plio-Pleistocene. Local and continent-wide extinction events in large-bodied carnivoran guilds from 1 to 2 Ma had a substantial effect on carcass availability and the risk to hominid scavengers. These structural changes in the carnivore guild may have provided an opportunity for hominids to widen their niche with respect to dietary behavior.

Africa↗

Visualization of opiate receptors and opioid peptides in sequential brain sections.

Autoradiographic and immunocytochemical studies were carried out on adjacent sections from formaldehyde-perfused rat brains in order to directly correlate the distribution of opiate receptors and opioid peptides. Perfusion fixation of the brains resulted in a partial loss of specific [3H]naloxone binding with essentially no change in the pharmacological properties of the remaining sites. When the distribution of sites was compared to that of enkephalin immunoreactivity in adjacent sections, striking correlations were observed in a number of areas throughout the neuraxis. Adjacent section autoradiography-immunocytochemistry should provide a useful tool for relating the anatomical distribution of opiate receptor subtypes to different opioid peptide neuronal systems.

Animals↗

Dynorphin immunocytochemistry in the rat central nervous system.

The distribution of dynorphin in the central nervous system was investigated in rats pretreated with relatively high doses (300-400 micrograms) of colchicine administered intracerebroventricularly. To circumvent the problems of antibody cross-reactivity, antisera were generated against different portions as well as the full dynorphin molecule (i.e., residues 1-13, 7-17, or 1-17). For comparison, antisera to [Leu]enkephalin (residues 1-5) were also utilized. Dynorphin was found to be widely distributed throughout the neuraxis. Immunoreactive neuronal perikarya exist in hypothalamic magnocellular nuclei, periaqueductal gray, scattered reticular formation sites, and other brain stem nuclei, as well as in spinal cord. Additionally, dynorphin-positive fibers or terminals occur in the cerebral cortex, olfactory bulb, nucleus accumbens, caudate-putamen, globus pallidus, hypothalamus, substantia nigra, periaqueductal gray, many brain stem sites, and the spinal cord. In many areas studied, dynorphin and enkephalin appeared to form parallel but probably separate anatomical systems. The results suggest that dynorphin occurs in neuronal systems that are immunocytochemically distinct from those containing other opioid peptides.

Animals↗