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Biomedical subjects

J Pearce

Publications and source records attributed to J Pearce.

At least 19 recordsLinked to original sources

Solution structure of the fifth repeat of factor H: a second example of the complement control protein module.

Modules which share the same consensus sequence are assumed to have common structural features, at the secondary and tertiary level. In order to test the extent of such similarities, it is necessary to examine the structures of several examples from each module family. Recently, the first three-dimensional structure of a complement control protein (CCP) module (the 16th repeat of human factor H, H16) was determined using a combination of two-dimensional NMR and simulated annealing [Norman, D.G., Barlow, P.N., Baron, M., Day, A.J., Sim, R.B., & Campbell, I.D. (1991) J. Mol. Biol. 219, 717-725]. Using the same techniques, the three-dimensional structure of a second CCP module (the 5th repeat of human factor H, H5) has now been determined. The primary sequence of H5 contains 17 residues which are identical and in equivalent position to those in H16. Thirteen of these 17 are part of the consensus sequence. The similarities between the secondary structure of H5 and that of H16 are extensive. This implies that the consensus sequence dictates a particular secondary structure. The tertiary structure of H5, a compact hydrophobic core wrapped in beta-strand and sheet, bears much overall resemblance to that of H16. However, there is a deletion in the first strand of H5, and an insertion in a loop, resulting in slightly shorter overall length. This is associated with a rearrangement of residues within the hydrophobic core. The side chain of the highly conserved Tyr29, which occupies a central position within the core of H16, lies on the periphery of the core of H5.

Amino Acid Sequence

Prison medicine.

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Family Practice

Choroid plexus carcinoma--responses to chemotherapy alone in newly diagnosed young children.

Choroid plexus carcinoma (CPC) arising in the infant poses several treatment dilemmas. The tumor is often not totally resectable at presentation given its large size and tendency to invade adjacent brain. Because of its predisposition to regrow and metastasize, some form of postoperative cytotoxic therapy is required. Chemotherapy (CHT), as opposed to radiotherapy (RT), has a more desirable risk/benefit role in infants, since it is relatively sparing of late neurologic sequelae. Three young male children presented with large intraventricular CPC at 9, 18, and 27 months of age. One child had subarachnoid metastases at diagnosis and the other two had localized disease. Subtotal resections were accomplished and all three required VP shunts. Initial CHT consisted of four monthly courses of cisplatin (20 mg/m2) and etoposide (100 mg/m2), both administered intravenously, daily, for five days. After four courses, two children had complete responses and one had stable disease. Additional CHT was given but one child developed a local recurrence and another diffuse CNS metastases. Both died with intratumoral hemorrhages at 5 and 57 months following diagnosis. The third child remains in continuous remission 46 months after diagnosis. None of the children received RT. Chemotherapy may permit long term deferral of RT. More aggressive CHT regimens should be explored in infants with CPC.

Antineoplastic Combined Chemotherapy Protocols

Sequence and embryonic expression of the murine Hox-3.5 gene.

The murine Hox-3.5 gene has been mapped and linked genomically to a position 18 kb 3' of its most 5' locus neighbour, Hox-3.4, on chromosome 15. The sequence of the Hox-3.5 cDNA, together with the position of the gene within the locus, show it to be a paralogue of Hox-2.6, Hox-1.4 and Hox-4.2. The patterns of embryonic expression for the Hox-3.5 gene are examined in terms of three rules, proposed to relate a Hox gene's expression pattern to its position within the locus. The anterior boundaries of Hox-3.5 expression in the hindbrain and prevertebral column lie anterior to those of Hox-3.4 and all other, more 5'-located Hox-3 genes. Within the hindbrain, the Hox-3.5 boundary is seen to lie posterior to that of its paralogue, Hox-2.6, by a distance equal to about the length of one rhombomere. Patterns of Hox-3.5 expression within the oesophagus and spinal cord, but not the testis, are similar to those of other Hox-3 genes, Hox-3.3 and Hox-3.4.

Amino Acid Sequence

A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants.

Modifiers of position-effect-variegation in Drosophila encode proteins that are thought to modify chromatin, rendering it heritably changed in its expressibility. In an attempt to identify similar modifier genes in other species we have utilized a known sequence homology, termed chromo box, between a suppressor of position-effect-variegation, Heterochromatin protein 1 (HP1), and a repressor of homeotic genes, Polycomb (Pc). A PCR generated probe encompassing the HP1 chromo box was used to clone full-length murine cDNAs that contain conserved chromo box motifs. Sequence comparisons, in situ hybridization experiments, and RNA Northern blot analysis suggest that the murine and human sequences presented in this report are homologues of the Drosophila HP1 gene. Chromo box sequences can also be detected in other animal species, and in plants, predicting a strongly conserved structural role for the peptide encoded by this sequence. We propose that epigenetic (yet heritable) changes in gene expressibility, characteristic of chromosomal imprinting phenomena, can largely be explained by the action of such modifier genes. The evolutionary conservation of the chromo box motif now enables the isolation and study of putative modifier genes in those animal and plant species where chromosomal imprinting has been described.

Amino Acid Sequence

Growth of inhibitory innervation in a lobster muscle.

The fine structure of inhibitory innervation to a limb muscle was examined in larval, juvenile, and adult lobsters. The innervation is essentially similar in qualitative features among these different stages, although there are some marked quantitative changes associated with growth. From being localized to discrete regions in the larval muscle, the inhibitory innervation spreads to groups of muscle fibers in the early juvenile muscle and to single fibers in the late juvenile and adult muscles. Concurrently, its neuromuscular synapses enlarge in area, become perforated, and acquire more active sites of transmitter release. Inhibitory nerve terminals occur in close proximity to their excitatory counterparts in the muscles of larval and early juvenile stages, although in later stages this juxtaposition occurs preferentially in some muscle fibers but not others. The inhibitory innervation is, nevertheless, much more restricted in occurrence than is the excitatory innervation.

Aging

Studies on the uptake, partition and retention of ionic and fallout radiocaesium by suckling and weaned lambs.

In the first part of this study 9 one week old lambs were fed, ad libitum, a liquid milk replacer diet containing 950 Bq 137Cs kg-1, for a period of 21 days. Absorption of the 137Cs from the milk replacer was over 90% during this period. The lambs were weaned onto a silage diet and then allocated to 2 groups (A and B). Group A was fed silage contaminated with fallout radiocaesium and group B with the same silage additionally contaminated with ionic 134CsCl. After a 3 week period the diets offered were changed over between the groups. During the silage feeding period the uptake of added ionic 134Cs was approximately twice that of fallout 134Cs present in the silage. These studies highlight the difficulties in using studies with the ionic form of the isotope to predict the animals' response to fallout contaminated feed.

Aging

Studies of the transfer of dietary radiocaesium from silage to milk in dairy cows.

Four experiments were carried out to examine the transfer of radiocaesium from silage to milk by dairy cows. Three experiments assessed the effects of stage of lactation, yield and the feeding of forage only on this transfer. It was found that maximum milk radiocaesium concentrations were achieved rapidly (within 5 days) after the start of feeding contaminated silage. The transfer coefficients (Fm) were low ranging from 0.002 to 0.003 d l-1. The fourth experiment examined the effects of alternately feeding silages, of relatively high and low radiocaesium contents, on a 2 d cycle on the milk radiocaesium content. It was observed that the milk radiocaesium content changed rapidly in response to the amount of radiocaesium ingested.

Accidents

Investigations of the use of clay minerals and prussian blue in reducing the transfer of dietary radiocaesium to milk.

Two experiments were performed with lactating dairy cattle to assess the efficacy of clay minerals and Prussian Blue (AFCF form) in controlling the transfer of dietary radiocaesium to milk. In Experiment 1, bentonite was included in the diet at 0, 300, 600 and 900 g d-1 and the transfer of radiocaesium from silage to milk was determined. Bentonite inclusion significantly (P less than 0.001) depressed the transfer of radiocaesium to milk with no benefit in increasing the dietary inclusion above 600 g d-1 when a 73% reduction was observed. In Experiment 2, the effectiveness of bentonite (300 g d-1), clinoptilolite (300 g d-1) and Prussian Blue (3 g d-1) as dietary additives was compared. All treatments significantly (P less than 0.001) depressed the transfer of dietary radiocaesium to milk. Clinoptilolite was less effective than bentonite and both treatments were considerably less effective than Prussian Blue, the reductions being 35%, 62% and 85% respectively.

Aluminum Silicates

The effects of prussian blue provided by indwelling rumen boli on the tissue retention of dietary radiocaesium by sheep.

A study was carried out to examine the effects of a form of Prussian Blue, provided by indwelling rumen boli, on the tissue retention of dietary radiocaesium by sheep. A single bolus providing 20-24 mg PB d-1 achieved a 42% reduction in tissue radiocaesium content. Multiple boli were not successful due to their loss from the rumen. The preparation used did not affect the health and well being of the animals.

Animals

Highly active neuromuscular system in developing lobsters with programmed obsolescence.

The primary locomotory apparatus in the three larval stages of the lobster, Homarus americanus, are paddlelike structures on the thoracic appendages called exopodites, which beat almost continuously. Consequently their power and return-stroke muscles are examples of highly active but short-lived neuromuscular systems. The muscles, which are well vascularized, are of the fast type with 2-3-micron sarcomere lengths and 6 thin filaments surrounding a thick one. The most striking feature, however, is the large volume of mitochondria making up 40-50% of the fiber. They appear as simple cylinders packed several layers deep along the periphery of the fiber and as large, multibranched forms distributed throughout the fiber and subdividing it into smaller units. The motor innervation to the return-stroke muscle is via 3 excitatory axons, which generate large junctional potentials and twitch contractions. The muscle is densely populated with large neuromuscular synapses, most of which have a well-defined active site or dense bar denoting the site of transmitter release. Altogether this motor system is specialized for prolonged activity. Atrophy of the neuromuscular system occurs by the late larval third stage. The muscle fibers lose their identity, fuse, and become vacuolated. The myofibrils condense and erode and the mitochondria are lost. Atrophy of motor innervation is gradual with individual axons dropping out. The largest axon providing most of the innervation is the first to degenerate. Early degenerative changes affect the axon and neuromuscular terminals but not the synaptic contacts, dense bars, and vesicles, which appear intact. Continued atrophy in the postlarval fourth stage reduces the exopodites to vestiges. Thus the return-stroke muscle of the larval exopodites in which muscle fiber and motoneurons are identifiable permits study of the interaction between a neuron and its target muscle undergoing programmed obsolescence.

Animals

Remodeling of nerves during claw reversal in adult snapping shrimps.

Adult snapping shrimps, Alpheus heterochelis, undergo a reversal of their claw laterality following removal of the major claw, a process in which the existing minor claw transforms into a major and a new minor regenerates at the old major site. During such reversals the nerves to the ganglion are remodeled from one claw type to the other. Conversion of the nerves from the minor to the major type occurs within several days after removal of the contralateral major claw and involves the rapid addition of large numbers of sensory axons together with deletion of a few. Thus modeling of the nerves is essentially complete within the first intermolt in tandem with changes in the motoneurons but well ahead of changes in the muscle and external morphology. Conversion of the major nerves to the minor type is via massive degeneration of sensory axons during the first and second intermolts because of the loss of their peripherally located cell bodies. This is followed by proliferation of largely unmyelinated axons in the third intermolt, some of which become myelinated in the subsequent intermolts. Thus remodeling of the major nerves to minor, which is associated with the loss of a claw and the regeneration of a new minor claw, is a more traumatic and prolonged process compared to the remodeling of the minor nerves to major which is associated with the transformation of an existing claw.

Animals

Neural attrition following limb loss and regeneration in juvenile lobsters.

Lobsters have considerable regenerative capacity, being able to regrow an entire, albeit smaller, limb in one intermolt. Whether there is a corresponding downscaling in the hemiganglion and its nerves to the regenerate side compared with its contralateral intact side was examined in juvenile lobsters which had undergone single or multiple (2, 4, and 6) cycles of limb loss and regeneration on the one side. The limbs studied were the enlarged thoracic chelipeds or claws which appeared as paired symmetrical cutter-type claws. The size of the regenerate limb, as indicated by its propus length, was approximately 30% smaller than its intact counterpart. Correspondingly, the total number of axons in the nerves to the regenerate side was smaller than on the intact, contralateral side. Such attrition was also by about 30% in lobsters experiencing a single cycle of limb loss and regeneration, but was considerably greater with multiple cycles. Tissue degeneration was occasionally seen in the nerves to the regenerate side but not in the ganglion. The paired hemiganglia were equivalent in all respects except in the size of the neuropil, which was smaller on the regenerate side compared with the contralateral intact side. Neuropil attrition was most marked with multiple cycles of limb loss and regeneration. Such attrition in nerve and neuropil are most likely due to the reduced number of sensory elements in the newly regenerated, but smaller, limb.

Animals