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Biomedical subjects

J H Adams

Publications and source records attributed to J H Adams.

At least 19 recordsLinked to original sources
PubMed1992

A family of erythrocyte binding proteins of malaria parasites.

Malaria erythrocyte binding proteins use the Duffy blood group antigen (Plasmodium vivax and Plasmodium knowlesi) and sialic acid (Plasmodium falciparum) on the erythrocyte surface as receptors. We had previously cloned the one P. vivax gene, the one P. falciparum gene, and part of one of the three P. knowlesi genes encoding these erythrocyte binding proteins and described the homology between the P. knowlesi and P. vivax genes. We have completed the cloning and sequencing of the three P. knowlesi genes and identified introns in the P. vivax and P. falciparum genes that correct the previously published deduced amino acid sequences. All have similar structures, with one or two exons encoding the signal sequence and the erythrocyte binding domain, an exon encoding the transmembrane domain, and two exons encoding the cytoplasmic domain with the exception of the P. knowlesi beta gene. The regions of amino acid sequence homology among all the genes are the 5' and 3' cysteine-rich regions of the erythrocyte binding domain. On the basis of gene structure and amino acid homology, we propose that the Duffy binding proteins and the sialic acid binding protein are members of a gene family. The level of conservation (approximately 70%) of the deduced amino acid sequences in the 5' cysteine-rich region between the P. vivax protein and the three P. knowlesi proteins is as great as between the three P. knowlesi proteins themselves; the P. knowlesi beta protein just 3' to this cysteine-rich region is homologous to the P. vivax protein but not to the other P. knowlesi proteins. Conservation of amino acid sequences among these organisms, separated in evolution, may indicate the regions where the adhesin function resides.

Amino Acid Sequence↗
PubMed1992

Subcurative chemotherapy and fatal post-treatment reactive encephalopathies in African trypanosomiasis.

The treatment of late-stage African sleeping sickness in man is often complicated by a post-treatment reactive encephalopathy. The bases of this pathological reaction was investigated in a mouse model of African trypanosomiasis. Subcurative treatment with diminazene aceturate, which did not clear parasites from the central nervous system, resulted in a post-treatment meningoencephalitis similar to that seen in man. By contrast, a curative regimen of melaminylthioarsenite and 5-nitroimidazole, which cleared parasites from the central nervous system, did not cause any pathological reaction in the mice. This result indicates that subcurative treatment leads to the development of the post-treatment encephalopathy. Evidence that this may also be the case in man was provided by the detection of trypanosome DNA with the polymerase chain reaction in the brains of 9 patients who had died as the result of a post-treatment reaction. Our findings suggest that more aggressive treatment regimens, which ensure the elimination of trypanosomes from the central nervous system, may prevent post-treatment reactions in patients.

Adolescent↗
PubMed1992

The cerebrovascular response to experimental lateral head acceleration.

A number of microvascular changes, such as the development of astrocyte lucency, increased endothelial pit/vesicle activity, development of crater like lesions, and endothelial microvilli have been reported after injury to the brain. Lateral head acceleration in the non-human primate, however, still provides the best experimental model for human diffuse axonal injury. No attempt has yet been made to document the spatial extent or time course of the microvascular response to acceleration injury to the head. We have examined the brains of baboons 1, 4, 6, and 12 h and 7 days after acceleration injury to the head to analyse the microvascular response. In the experimental animals there was a short-term rise in intracranial pressure followed by a long-term resolution, and a reduction in both mean arterial blood pressure and cerebral perfusion pressure which, however, never dropped below 75% of baseline for more than 5 min after injury in any animal. We found evidence for extravasation of blood in a small number of blood vessels in all parts of the brain. Interendothelial tight junctions are not disrupted. Pit/vesicle activity rises in the 1st h in the occipital cortex, but not until 4 h in the frontal cortex, and remains elevated for at least 7 days. There is little change in the thalamus. Development of microvilli is most rapid in the frontal cortex with peak values at 1 h, but slower in the thalamus and occipital cortex where peak values are only obtained at 6 h. Highest numbers of microvilli occur in parasagittal regions of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Acceleration↗
PubMed1992

Hippocampal pathology in fatal non-missile human head injury.

The hippocampus has been known to be involved in fatal non-missile human head injury, although detailed histopathology of this lesion has yet to be described. This report documents the frequency and distribution of hippocampal damage in a consecutive series of 112 fatal human non-missile head injuries. Damage to the hippocampus was noted in 94 cases (84%). Lesions always involved the CA1 subfield and were bilateral in 70 cases. Other subfields of the hippocampus were involved less frequently. Lesions were focal in the majority of cases (58%). Pathological evidence of high intracranial pressure was present in 86% of the cases. Hypoxic brain damage in other regions of the brain was present in 74% of cases. Thus, the hippocampus is frequently damaged in fatal non-missile human head injury. The pattern of this damage is similar to that observed in experimental head injury. Hypoxia and high intracranial pressure are likely to contribute to the occurrence of human traumatic hippocampal damage but other mechanisms, such as excitotoxicity, are likely to be operative.

Adolescent↗
PubMed1992

Changes in the choroid plexus, responses by intrinsic epiplexus cells and recruitment from monocytes after experimental head acceleration injury in the non-human primate.

We have examined, by scanning and transmission electron microscopy, morphological changes in the choroid plexus of the lateral ventricles of the non-human primate brain after lateral head acceleration. We demonstrate passage of plasma and blood cells either through tears in blood vessels and the choroidal epithelium, or through the cells of the choroidal epithelium, 20 min after injury, together with morphological changes in that epithelium. At 3 and 4 h small cells with a reniform nucleus accumulate in the connective tissue core of the choroid plexus. We suggest that these are monocytes. At 6 and 12 h cells can be seen in enlarged intercellular spaces within the choroidal epithelium. These cells possess surface ruffles and we suggest that they are monocytes differentiating into macrophages and epiplexus cells. Further evidence for transepithelial migration of monocytes/macrophages is obtained at 7 days. However, at 28 days all blood has been removed from the surface of the choroid plexus and epiplexus cells possess an appearance typical of that in uninjured animals. The possible sources of epiplexus cells are discussed with reference to studies of responses after brain insult and of development. We have obtained no evidence in support of emperipolesis by monocytes through the choroidal epithelium. We suggest that monocytes/macrophages migrate, via an intercellular route, to differentiate into epiplexus cells, thus providing additional numbers of epiplexus cells after head injury.

Acceleration↗
PubMed1992

Diffuse axonal injury caused by assault.

The case reports of 50 fatal head injuries caused by assault and managed at the Institute of Neurological Sciences, Glasgow, were reviewed. Fifteen cases had diffuse axonal injury. Diffuse axonal injury is a well recognised type of brain damage brought about by a head injury, usually as a result of a road traffic accident or fall from a height. It does not seem to be widely appreciated that it may also occur as a result of an assault. This has important medicolegal implications.

Adolescent↗
PubMed1991

Blocking of the receptor-mediated invasion of erythrocytes by Plasmodium knowlesi malaria with sulfated polysaccharides and glycosaminoglycans.

Invasion of human erythrocytes by Plasmodium knowlesi requires the Duffy blood group antigen. P. knowlesi merozoites synthesize a 135-kDa polypeptide which binds to the Duffy antigen with receptor-like specificity. In this study, we show that the sulfated polysaccharide fucoidan and the glycosaminoglycan dextran sulfate inhibit the binding of the 135-kDa polypeptide to human Duffy-positive and rhesus erythrocytes while the chondroitin sulfates do not. Fucoidan and dextran sulphate also blocked the in vitro invasion of human Duffy b and rhesus erythrocytes cells by P. knowlesi merozoites. These inhibitors were more effective at blocking the binding of the 135-kDa polypeptide to human Duffy b erythrocytes than to rhesus erythrocytes, which correlated with them having a greater inhibitory effect on invasion of merozoites into human than into rhesus erythrocytes. The blocking by these sulfated sugars is not related to charge density on the polysaccharides; fucoidan with a relatively low charge density blocks binding of the 135-kDa polypeptide at 4 micrograms/ml, while the highly negatively charged chondroitin sulfates do not block binding even at the concentration of 1 mg/ml. Furthermore, fucoidan-Sepharose bound and removed the 135-kDa polypeptide from parasite culture supernatants with a selectivity equal to that of the Duffy blood group antigen. The negatively charged sulfate groups on fucoidan and dextran sulfate and the conformation in which they are held possibly mimic similarly charged groups on the Duffy antigen which bind the 135-kDa P. knowlesi polypeptide.

Animals↗
PubMed1991

Focal axonal injury: the early axonal response to stretch.

The development of a model for axonal injury in the optic nerve of the guinea pig has allowed analysis of early morphological changes within damaged axons. We provide evidence that the initial site of damage after stretch is the nodes of Ranvier, some of which develop 'nodal blebs'. The development of nodel blebs is correlated with the loss of subaxolemmal density, disruption of the neurofilament cytoskeleton and aggregation of membranous profiles of smooth endoplasmic reticulum. Nodal blebs are numerous 15 min after injury but less so at later survivals. The glial-axonal junction is intact at early survivals in damaged nodes. Marked accumulation of membranous organelles occurs in the paranodal and internodal regions adjacent to damaged nodes between two and six hours and is correlated with disruption of the myelin sheath. Axotomy and the formation of degeneration bulbs occurs between 24 and 72 h. The area of axonal injury is invaded by phagocytic cells by 72 h and large numbers of myelin figures occur within the neuropil until 14 days. The results are compared with those of other studies of diffuse axonal injury and other neuropathies. The time course of axonal changes is more rapid than during Wallerian degeneration. Our data from longer surviving animals is exactly comparable with published data. We are confident that the principal site of axonal injury is the node of Ranvier. We suggest that damage at the node results in disruption of axonal transport, which in turn leads to a cascade of events, culminating in axotomy between 24 and 72 h after the initial insult.

Animals↗
PubMed1991

Cloning of the Plasmodium vivax Duffy receptor.

Plasmodium vivax and Plasmodium knowlesi merozoites invade only Duffy blood group-positive human erythrocytes. Soluble P. vivax and P. knowlesi merozoite proteins of 135 kDa bind specifically to Duffy blood group determinants. The gene encoding a member of the Duffy receptor gene family of P. knowlesi has been cloned. We report here the molecular cloning of the presumptive Duffy receptor gene of P. vivax, using the P. knowlesi gene as a probe. There is a single gene in P. vivax which codes for a protein of 1115 amino acids. The deduced amino acid sequence predicts a putative signal sequence at the amino-terminus and a transmembrane region followed by 45 amino acids at the carboxy-terminus. The three introns found at the 3' end of the P. knowlesi gene were conserved in P. vivax, including high homology for the sequences of the introns. Comparison of the portion of the proteins amino to the transmembrane region between P. vivax and the partial sequence of P. knowlesi indicated at least three domains. Two homologous regions were separated by a non-homologous region. The cysteines in the homologous regions were conserved in number and position, indicating that the folding is similar and suggesting that these regions may be the Duffy blood group binding domains. In both P. vivax and P. knowlesi, the non-homologous region is hydrophilic and proline-rich, although the position of the prolines is not conserved. As prolines tend to stiffen a protein, this region may act as a 'hinge region' similar to those in the immunoglobulin gene family.

Amino Acid Sequence↗
PubMed1991

Selective vulnerability of hippocampal neurons in acceleration-induced experimental head injury.

Traumatically induced subtotal hippocampal neuronal loss traditionally has been considered a consequence of intracranial hypertension and impaired cerebral perfusion. We have examined the frequency and distribution of hippocampal lesions in an acceleration model of brain injury in 54 anesthetized nonhuman primates undergoing physiologic monitoring and subjected postinjury to comprehensive neuropathologic examination. Hippocampal lesions occurred in 32/54 animals (59%). These lesions always involved the CA-1 hippocampal subfield and were bilateral in 24 animals. Hippocampal involvement was not associated with marked elevation of intracranial pressure or depression of cerebral perfusion pressure. These lesions occurred in the absence of involvement of other brain regions considered selectively vulnerable to hypoxic insults. Hippocampal damage occurred in 46% of animals with mild injury characterized by brief periods of unconsciousness and no residual neurologic deficit. Ninety-four percent of animals with severe injuries and prolonged posttraumatic coma had hippocampal involvement. Traumatically induced selective neuronal necrosis of the hippocampus is a specific lesion not explained by the conventional mechanistic theories of head injury. An alternative hypothesis, such as excitotoxicity involving glutamate or other neurotransmitters, may account for the lesions demonstrated in this study.

Acceleration↗
PubMed1991

The microvascular response to stretch injury in the adult guinea pig visual system.

In a variety of brain injury models, both reactive axonal change and microvascular abnormalities occur. Development of a stretch injury model in the guinea pig optic nerve has allowed for the characterization of the early axonal response to injury. In this same model, we have now attempted to characterize those morphologic changes occurring in the visual system microvasculature after injury. Thirty adult guinea pigs were subjected to axonal stretch injury and killed at posttraumatic survival periods ranging from 10 minutes to 14 days. Twenty animals were examined by scanning electron microscopy (SEM) for the detection of posttraumatic changes in the surface morphology of the microvasculature, and 10 animals were processed for transmission electron microscopy (TEM) analysis. Through this approach, increased pit vesicle activity and formation of endothelial microvilli were recognized within 10 minutes of injury. Pit vesicle activity returned to control levels by 2 hours. The formation of endothelial microvilli was widespread, affecting the microvessels in both the stretched and unstretched optic nerves and in the chiasm. The greatest response developed most slowly in the stretched nerve, and it was faster but less marked in the unstretched nerve and chiasm. Microvilli were more numerous in larger vessels. Related astrocytic swelling/lucency was not apparent until 6 hours after injury. The astrocyte response was less marked than that documented after brain injury. The results of this investigation demonstrate a widespread microvascular response to stretch injury of the guinea pig optic nerve. Comparison with the documented responses to traumatic brain injury indicates different rates of response to different types of insult.

Animals↗
PubMed1991

Glial swelling following human cerebral contusion: an ultrastructural study.

The ultrastructural features of cerebral contusion seen three hours to 11 days after head injury were studied in 18 patients undergoing surgery. Massive astrocytic swelling ("cytotoxic" oedema) was seen three hours to three days after injury, maximal in perivascular foot processes, and compressing some of the underlying capillaries. The tight junctions were not disrupted. Neuronal damage was most marked three to 11 days after injury. The pathophysiological mechanisms leading to oedema formation and neuronal degeneration are discussed.

Adult↗
PubMed1991

Localisation of calcium ions and calcium-ATPase activity within myelinated nerve fibres of the adult guinea-pig optic nerve.

There is no published description of the distribution of free Ca2+, nor of the distribution of Ca(2+)-ATPase activity associated with the maintenance of low axoplasmic Ca2+ concentrations, in normal central myelinated nerve fibres. We have used the oxalate-pyroantimonate technique to localise free Ca2+, together with the lead-citrate technique to localise Ca(2+)-ATPase activity within myelinated fibres from the adult guinea-pig optic nerve. Pyroantimonate precipitate occurred within the axoplasm at nodes of Ranvier and the internode, at areas of myelin disruption, within Schmidt-Lanterman incisures (SLI) and glial paranodal loops. But precipitate was absent from the axoplasm beneath SLI and at the paranode. Ca(2+)-ATPase activity was localised in axonal smooth endoplasmic reticulum (SER), the outer membrane of mitochondria, the nodal axolemma, the glial membranes of the paranodal loops, the SLI and the external aspect of the myelin sheath. We have demonstrated large domains within the axons of CNS fibres where calcium is present or absent. Moreover, we have shown that, where calcium is absent, there is localisation of Ca(2+)-ATPase activity, which would serve to remove calcium from the adjacent axoplasm. Our results are compared with information obtained from PNS fibres and some differences of distribution discussed.

Animals↗
PubMed1990

The Duffy receptor family of Plasmodium knowlesi is located within the micronemes of invasive malaria merozoites.

Plasmodium vivax and Plasmodium knowlesi merozoites invade human erythrocytes that express Duffy blood group surface determinants. A soluble parasite protein of 135 kd binds specifically to a human Duffy antigen. Using antisera affinity purified on the 135 kd protein, we cloned a gene that encodes a member of a P. knowlesi family of erythrocyte binding proteins. The gene is a member of a family that includes three homologous genes located on separate chromosomes. Two genes are expressed as major membrane-bound products that give rise to soluble erythrocyte binding proteins: the 135 kd Duffy binding protein and a 138 kd protein that binds only rhesus erythrocytes. These different erythrocyte binding specificities may result from sequence divergence of the homologous genes. The Duffy receptor family is localized in micronemes, an organelle found in all organisms of the phylum Apicomplexa.

Amino Acid Sequence↗