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Biomedical subjects

J M Lawrence

Publications and source records attributed to J M Lawrence.

At least 91 records · Page 5Linked to original sources

Membrane specializations and extracellular material associated with host astrocytes in peripheral neural transplants.

The work of Aguayo and colleagues [Aguayo, David and Bray (1981) J. Exp. Biol. 95, 231-240] demonstrates that grafts of peripheral neural tissue are able to induce regenerative elongation of cut axons in the adult central nervous system. Elucidation of the mechanism of this response requires an understanding of the cellular interactions induced by these types of transplant. In previous studies [Zhou, Lawrence, Morris and Raisman (1986) Neuroscience 17, 815-827; Zhou, Lindsay, Lawrence and Raisman (1986) Neuroscience 17, 803-813] we have transplanted decapsulated adult superior cervical sympathetic ganglia or nodose ganglia into either the septal nuclei or the choroid fissure of adult syngeneic rat hosts. We found that host astrocytes invade the transplants along Schwann cell fascicles and around blood vessels. This raises the questions of what form the migrating astrocytes take, what routes they follow, and what is their fate. In the present study we have taken advantage of the fact that at longer survivals astrocytes accumulate as "paravascular cuffs", and we show that they have several specialized ultrastructural features, such as plasmalemmal caveolae, desmosomes, hemidesmosomes and accumulations of extracellular material. The specific stimuli inducing (or enhancing) these astrocytic specializations and their significance in relation to the wider morphogenetic events induced by peripheral neural transplants remain to be elucidated. However, the observations are further evidence of the remarkable mobility and plasticity of central astrocytes in transplantation situations, and in particular emphasize the involvement of the cell surface and its relationship to extracellular matrix.

Animals↗

Altered locomotor activity in neuropsychiatric patients.

Movement was monitored continuously for 24-48 hours in representative neuropsychiatric patients, using a wrist-worn portable piezoelectric activity monitor with solid-state memory. Striking differences were observed in both circadian and more rapid (ultradian) rhythms between these patients and normal controls of a similar age. We found a loss of circadian rhythm following stroke, and a marked 4-hour activity rhythm in patients with dementia and brain tumor. These results may provide insights into the neural substrate of activity rhythms and may lead to better care of neuropsychiatric patients.

Affective Disorders, Psychotic↗

Extent of survival and vascularization of adult superior cervical sympathetic or nodose ganglia transplanted into the septal nuclei or choroid fissure of adult rats.

Adult superior cervical sympathetic ganglia were auto-transplanted, and adult nodose ganglia were homografted into the septal nuclei or the choroid fissure of adult Wistar rats. At times from 4 h to 9 weeks after operation, the distribution of surviving transplanted neurons was compared with the development of the transplant vascularization, as visualized by transcardial Indian ink filling of the host vascular system. Within 24 h, the ganglionic neurons and Schwann cells of the interior of the transplants in both sites were necrotic. The surviving neurons and Schwann cells formed a shell, occupying those areas of the transplant periphery which were in direct contact with the host circulation. Occasional ink-filled vessels were evident at this time in transplants in the choroid fissure, but there were none in the septal nuclei, where vessels did not appear until the next day. Blood vessels reached the centre of the ganglia by 3-4 days in the choroid fissure and one week in the septal nuclei, the finest diameter capillaries forming last. At longer survivals there was a slow loss of neurons, notable between 1 and 2 months, and leading progressively (especially in the septal transplantation site) to the disappearance of all but a very small number of ganglionic neurons. The general findings were similar for both types of ganglion, and in both sites, but the initial cell loss was much greater for both types of ganglia in the septum (over 90%) as compared with about a 50% loss in the choroid fissure. The initial rapid cell loss was probably a result of ischaemia. The subsequent, slow progressive loss may be associated with failure to make or receive neuronal connections, or the absence of appropriate growth factors.

Animals↗

Migration of host astrocytes into superior cervical sympathetic ganglia autografted into the septal nuclei or choroid fissure of adult rats.

Adult astrocytes and their processes, identified by glial fibrillary acidic protein immunohistochemistry and by electron microscopy, migrate into superior cervical ganglia auto-transplanted into the choroid fissure or septal nuclei of adult rats. Migration routes were along the blood vessels, and along the Schwann cell bundles of the transplant. Ultrastructurally, astrocytic processes could be seen to lie in direct contact with Schwann cell processes within the basal lamina enwrapping the Schwann cell and its associated axons. Around the region of the host/transplant interface, the astrocytes were transformed into flattened cells with many short, irregular, fringe-like processes, but within the depths of the transplant mass they resumed a more stellate configuration. Glial fibrillary acidic protein immunoreactivity was present within the intrinsic satellite and Schwann cells of the grafted ganglia, but at a much lower level than in the host astrocytes. It is concluded that reactive astrocytes from adult host central nervous system migrate into peripheral ganglionic transplants, where they differentiate and establish organized arrangements with the ganglionic elements.

Animals↗

Vascular and astrocytic reactions during establishment of hippocampal transplants in adult host brain.

Hippocampal primordia were transplanted into the hippocampus or septum of adult rats, and the development of the transplant vasculature studied by light microscopy after India ink perfusion, by immunohistochemistry of collagen type IV (as a marker for basal lamina), and by electron microscopy. From the basal lamina of all vessel types arise streamers of basal lamina which clothe the external plasmalemmal surfaces of adjacent astrocytic processes and invaginate them, suggesting that the astrocytic processess may be involved in directing the assembly of this basal lamina. A few host blood vessels reach the transplants by one day after operation, and probably re-perfuse existing transplant vessels. Two main types of vascular reaction occur over the next week. The first is the formation of wide-diameter reactive vessels with an expanded perivascular space, engorged with mesodermal cells (such as macrophages). The second is the formation of dilated, thin-walled, marginal vessels, from which numerous fine capillaries arise. The formation of astrocyte-apposed basal laminar streamers may be important in the development of channels along which the endothelial cells of the newly growing capillaries later migrate. By one month after operation, the transplant vasculature consists of small capillaries whose size, distribution and density are comparable to those of the host. This paper describes the vascular changes which occur when embryonic central nervous transplants become established in the brain of adult hosts, and indicates that one of the characteristic features is the formation of basal lamina-lined channels invaginating the perivascular astrocytes.

Animals↗

Effects of spinal cord transection on synapse numbers and biochemical maturation in rat lumbar sympathetic ganglia.

The effects of interruption of descending central pathways on the morphological and biochemical ontogeny of peripheral sympathetic ganglia were examined in the sixth lumbar (L6) sympathetic rat ganglia. Previous studies defined the normal maturation of presynaptic choline acetyltransferase (CAT) activity, postsynaptic tyrosine hydroxylase (T-OH) activity, and total protein in the L6 ganglion. In the present investigations ganglion synapse numbers and adrenergic neuron numbers were examined in transected and sham-operated littermate controls 6 weeks after surgery at 10 days of age and correlative biochemical studies were performed. Spinal transection resulted in a reduction in synapse number on ganglion cell bodies (53.5% reduction) and neuronal processes (55.8% reduction). This abnormality in synapse number was associated with a reduction of CAT activity to 56% of control. Although T-OH activity also failed to develop normally and was 25% of control, there was no associated alteration in adrenergic neuron number. These studies suggest that descending central pathways regulate the maturation of presynaptic cholinergic terminals (and hence synapse number) in sympathetic ganglion and that CAT activity serves as an accurate marker for these terminals. Additionally, the ontogeny of ganglion T-OH activity is altered by central lesions and this effect is not secondary to a decrease in adrenergic neuron number.

Animals↗

Clotted false lumen: reappraisal of indications for medical management of acute aortic dissection.

Evidence of a clotted false lumen in patients with acute aortic dissection has been considered to be a primary indication for medical rather than surgical therapy. A review of recent publications shows that 14 of 15 such patients survived with medical management. We present three patients who had radiographic, surgical, or necropsy evidence of acute aortic dissection with a clotted false lumen, who suffered further dissection in spite of adequate medical therapy. Our experience indicates that this condition is not as stable as it has been considered in the past. Consequently, we believe that great caution should be exercised in the application of medical therapy and in the follow-up of patients who demonstrate evidence of a clotted false lumen in an acute aortic dissection. Surgical treatment is indicated at the earliest sign of clinical or radiographic deterioration during medical therapy.

Acute Disease↗

Reduction of Nitrate and Nitrite in Lambsquarters (Chenopodium album) Biotypes Resistant and Susceptible to Atrazine Toxicity.

The nitrite-reducing activity of the normal susceptible biotype of lambsquarters (Chenopodium album L.) was strongly inhibited by atrazine in the assay medium, both in the case of the in vivo assays of leaf discs in light, and in vitro photoreduction assays of crude extracts. In vitro assays of crude extracts with methylviologen or ferredoxin supplying the reducing potential were not inhibited by atrazine. In the resistant biotype, inhibition of nitrite reduction did not occur with any of the above assays. Thus, it appears that atrazine does not inhibit nitrite reductase itself, but rather the availability of photosynthetically supplied electrons for the reduction. Atrazine had no effect when added to the media for either in vivo or in vitro assays of nitrate reduction by either the susceptible or resistant biotype.Young lambsquarters plants were treated with atrazine by spraying the leaves at a rate which was lethal for susceptible plants after 5 or 6 days, but had little effect on the resistant biotype. Nitrite did not accumulate in either biotype, but remained present at the level of about 0.1 microgram nitrite N per gram fresh weight. The nitrate content of susceptible-type leaves did increase to two or three times the initial level, during the first four days after spraying. Usually the only visible effect on the plants during this time was a decreased growth rate. Twenty-four hours after spraying the following activities had fallen to 25% or less of the activities of solvent-sprayed control plants: in vivo nitrite reductase, in vivo nitrate reductase, in vitro NADH-nitrate reductase, in vitro reduced flavin mononucleotidenitrate reductase, and in vitro NADH-diaphorase. In these atrazine-treated plants, in vitro nitrite reductase activity with reducing potential supplied by methylviologen was not affected, nor were any of the above activities in leaves of atrazine-treated resistant plants. The abrupt fall in nitrate reductase represents an effect of atrazine not directly related to inhibition of photosynthesis.

Journal Article↗

Decentralization of the superior cervical ganglion in neonates impairs the development of the innervation of the iris. A quantitative ultrastructural study.

The superior cervical sympathetic ganglion was decentralized unilaterally by section of the preganglionic chain in 2- or 4-day-old rats. Twenty-one days post-operatively the dilator muscle of the iris was examined electron microscopically. Quantitative estimates demonstrated that there was a reduction both in the numbers of axon bundles and of individual axons in the iris innervated by the deafferented ganglion as compared with its fellow of the contralateral control side.

Animals↗

Adenocarcinoma of the frontal sinus with extension to the brain in a horse.

A space-occupying intracranial mass was diagnosed in a horse. The clinical findings included blindness, circling to the right, apprehension, anorexia, weight loss, and leaning against the stall. On ophthalmoscopic examination, the most striking observation was complete bilateral devascularization of the retinas. The horse was euthanatized and necropsied. Necroscopy revealed the mass to occupy the olfactory and frontal areas of the left hemisphere of the brain and part of the left frontal sinus. Microscopically, the mass was an adenocarcinoma and probably arose from the lining epithelium of the sinus or from the subepithelial glands.

Adenocarcinoma↗