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Biomedical subjects

P Rooney

Publications and source records attributed to P Rooney.

At least 19 recordsLinked to original sources

The role of hyaluronan in tumour neovascularization (review).

Tumour growth and metastasis are totally dependant upon neovascularization. The target cell for tumour neovascularization is the blood-vessel endothelial cell, and specific angiogenic molecules produced or induced by the tumour are believed to initiate the process. In this report, we review one of these angiogenic molecules, the glycosaminoglycan hyaluronan (HA), which appears to have differing roles in neovascularization depending on its molecular mass. High-molecular-mass HA is anti-angiogenic whereas oligosaccharides of HA, of specific size, actively stimulate endothelial-cell proliferation and migration, 2 of the key events associated with neovascularization, and induce angiogenesis in vivo. We provide details of the action of HA oligosaccharides on endothelial cells, from binding to cell-surface receptors, through activation of signal transduction pathways and gene expression to protein synthesis, cell proliferation and cell migration. We also suggest a model to account for HA of differing molecular mass being present, at different locations, within a single tumour and how this HA aids both general tumour growth and tumour metastasis.

Cell Division

Dexamethasone treatment of lipopolysaccharide-induced meningitis in rabbits that mimics magnification of inflammation following antibiotic therapy.

The objective of adjunct anti-inflammatory therapy of bacterial meningitis is the containment of heightened inflammation caused by lysis of bacteria by antibiotics. This can be modelled by giving two consecutive intra-cisternal injections of lipopolysaccharide (LPS) to rabbits, the first at 0 h to induce inflammation to mimic that occurring during the proliferation of bacteria in the cerebrospinal fluid (CSF), and the second at 6 h to mimic inflammation subsequent to antibiotic-induced bacterial lysis. Injection of 2.5 ng of LPS induced pleocytosis at 4 h which was preceded by a peak of tumour necrosis factor (TNF) activity at 2 h. A subsequent injection of 25 ng of LPS at 6 h induced second peaks of pleocytosis and CSF TNF. Dexamethasone (1.5 mg/kg, i.v.) administered 15 min or 1 h before the second injection of LPS tended only to reduce CSF TNF, but effectively prohibited further pleocytosis. Brain TNF alpha mRNA levels were unchanged at 6 and 7 h after LPS injection, and were unaffected by dexamethasone. These results indicate that the subarachnoid space is distinct from the general circulation in that the TNF-producing cells present do not display a hypo-responsive state towards LPS as occurs when LPS is injected systemically. Furthermore, dexamethasone is able to attenuate the secondary inflammatory response resulting from a second LPS injection without eliminating a second peak of TNF activity.

Animals

Essentials of obstetric anaesthesia.

Obstetric anaesthesia is unique in that there is a "double patient" for whom the anaesthetic staff, medical and nursing, have responsibility. The question must also be asked, "Why anaesthesia in obstetrics anyway?" There is one main reason, with two applications-pain relief for both labour and for operative delivery. It is, therefore, professionally prudent to be aware of the special physical challenges presented.

Anesthesia, Obstetrical

Anaesthesia for neurosurgery--essentials of anaesthesia.

Paul Rooney continues his series of articles on anaesthetics. In approaching the topic of anaesthesia for neurosurgery he is aware of the need for a clear understanding of basic anatomy and physiology of the central nervous system.

Anesthesia

Application of angiogenic oligosaccharides of hyaluronan increases blood vessel numbers in rat skin.

Angiogenic oligosaccharides of hyaluronan were applied to the backs of young, adult male rats and the number of blood vessels, within a depth of 136 microns beneath the base of the epidermis, were evaluated. Application of hyaluronan oligosaccharides significantly increased the mean number of blood vessels/mm skin length in six of 11 treated rats when compared with controls. Application of radiolabeled hyaluronan oligosaccharides to skin of one rat demonstrated a penetration to a depth of approximately 800 microns, suggesting that the blood vessels beneath the epidermis would be exposed to the hyaluronan. Hyaluronan has previously been shown to stimulate endothelial cell proliferation; we demonstrate here that these hyaluronan oligosaccharides also specifically stimulate endothelial cell migration. This action of hyaluronan oligosaccharides may prove useful in retarding blood vessel paucity and degeneration observed during the ageing process and following radiotherapy.

Animals

Adult intubation for beginners.

The UKCC's 'Scope of Professional Practice' validly points out that, 'Practice takes place in a context of continuing change and development' partly 'as a result of new approaches to professional practice'. Consequently, demands are made on educational institutions to prepare professionals for new practice. One of the new skills, which is now being taught to nurses on the Anaesthetic Nursing Course at the Eastern Area College, is that of endotracheal intubation. Bearing in mind the all-important proviso that 'As a registered nurse, midwife or health visitor, you are personally accountable for your practice', it is essential that post registration education 'equips practitioners with additional and more specialist skills necessary to meet the special needs of patients and clients'. This article is therefore designed as an introduction to the basic rationale, anatomy and procedural skills necessary for safe intubation.

Humans

Cartilage and bone formation in repairing Achilles tendons within diffusion chambers: evidence for tendon-cartilage and cartilage-bone conversion in vivo.

Rodent Achilles tendons were subjected to midpoint tenotomy and allowed to recover for various times in situ before the operated tissue was removed, placed into a Millipore diffusion chamber, and inserted intraperitoneally into syngeneic hosts. Diffusion chambers were then removed at weekly intervals, such that the total time after the operation (i.e., time allowed to recover in situ plus time within the diffusion chamber) was up to 8 weeks, and examined histologically. Ectopic cartilage was produced within the diffusion chamber after a total of 4 weeks but only if the first 2 weeks of recovery were in situ. With increasing time, calcified cartilage, osteoid, and bone were also observed. Overall, the evidence suggests that the cartilage forms via a direct conversion from tendon tissue and that the bone may form as a result of differentiative changes of hypertrophic chondrocytes.

Achilles Tendon

Pre-irradiation of tissue culture flasks leads to diminished stem and progenitor cell production in long-term bone marrow cultures.

Empty plastic tissue culture flasks were exposed to X-irradiation doses of 0.3-10.0 Gy, prior to the establishment of long-term bone marrow cultures. During the course of a 10 week culture period, all irradiated plastic flasks exhibited a dramatic decrease in the number of both haemopoietic stem cells and myeloid progenitor cells, in the non-adherent layer, when compared with controls. This decrease was not due to a decrease in the number of non-adherent cells produced. Histological examination of non-adherent cells showed an increase in mature granulocytic cells with few blast cells. Morphologically, the adherent layers of irradiated flasks demonstrated a delay in appearance or absence of fat cell production. X-irradiation of glass tissue culture flasks had no deleterious effect.

Adipose Tissue

Inverse relationship between hyaluronan and collagens in development and angiogenesis.

The extracellular matrix plays a vital role in regulating normal tissue development and function--largely via the specific arrangement of macromolecules such as collagens, proteoglycans, glycosaminoglycans and glycoproteins. Previous reports have concentrated on associations between combinations of collagens/proteoglycans, collagens/glycoproteins and proteoglycans/glycosaminoglycans whilst little information is available on associations between collagens and free glycosaminoglycans. In this review, we discuss possible associations between collagens and the glycosaminoglycan hyaluronan; macromolecules which are known to exhibit changes in amount and composition during development and under pathological conditions. We demonstrate two types of collagen/hyaluronan association in vivo: the first, during the formation of extracellular matrix structures where neither collagens nor hyaluronan are degraded, resulting in the regulation of collagen fibrillogenesis, and the second, involving an inverse correlation between collagen synthesis and hyaluronan degradation and vice versa. We suggest that associations between collagens and hyaluronan play an important role in the initiation and maintenance of angiogenesis and put forward a model of cartilage vascularisation which relies on these associations.

Animals

Angiogenic oligosaccharides of hyaluronan enhance the production of collagens by endothelial cells.

The present study demonstrates a relationship between angiogenic oligosaccharides of hyaluronan (HA) and the production of collagens during the process of angiogenesis in vivo and in vitro. The addition of angiogenic oligosaccharides of HA to the chorioallantoic membrane of the chick embryo induced a deposition of collagen fibrils. The treatment of sub-confluent cultures of bovine aortic endothelial cells with the same oligosaccharides (1 microgram/ml) increased the uptake of [3H]proline by approximately 60%. SDS-polyacrylamide gel electrophoresis of treated cultures demonstrated the enhanced synthesis of type I and type VIII collagens. The production of type VIII collagen was confirmed by western blotting and immunocytochemistry using antibodies to sheep and bovine type VIII collagen. Type VIII collagen is a short chain collagen that has a high degree of homology to cartilage-specific type X collagen. The biological functions of type VIII and type X collagens are unknown. We have suggested that the two collagens play a role in the process of angiogenesis.

Animals

Endochondral ossification and de novo collagen synthesis during repair of the rat Achilles tendon.

Ectopic endochondral ossification is the inevitable consequence of midpoint tenotomy of the rat Achilles tendon. After tenotomy, the tendon stumps retract and the intervening space fills with granulation tissue. The initiation of chondrogenesis is indicated by pre-chondrocytic cells forming a "whorled" pattern, both at the tendon stumps and within the granulation tissue and later clearly differentiating into cartilage nodules. The chondrocytes rapidly "hypertrophy" exhibiting an orientation similar to that in epiphyseal growth plates. The nodules of cartilage are then replaced, by bone. During this total process, a temporal and spatial pattern of new collagen synthesis can be demonstrated, both biochemically and immunocytochemically. Both the cartilage and the subsequent bone closely resemble the tissue in developing long bones enabling this model to be used to study the initial switching on of normal chondrogenesis and osteogenesis in a system not normally programmed to do so.

Achilles Tendon

Bone-marrow-derived chondrogenesis in vitro.

Bone marrow stromal cells from embryonic, neo-natal and adult chickens were grown in vitro over a 21-day period. Marrow stromal cells from embryonic and neonatal chicks produced clonally derived chondrocytic colonies. The cells within the colonies were surrounded by a refractile, Alcian-blue-positive matrix and their cartilagenous nature was shown biochemically and immunocytochemically by the synthesis of collagen types II and X. The ability of chick bone marrow cells to form chondrocytic colonies decreased during development and was lost by adulthood. In addition to chondrocytic colonies, fat cells and fibroblasts were also observed in the cultures. Our data demonstrate that chick bone marrow stroma contains cells that are capable of differentiating along different pathways within the same culture, providing further evidence for the presence in bone marrow of a stromal stem cell.

Aging

The development of the perichondrium in the avian ulna.

The development of the perichondrium surrounding the ulna of chick embryos was examined between stages 26 and 34 (Hamburger & Hamilton, 1952), i.e. 5.5-8 d of incubation. The first appearance of a barrier between cartilage and adjacent tissue was observed at stage 27 when cells were arranged circumferentially around the central flattened core, but no true perichondrium was seen until chondrocyte hypertrophy began at stage 30. At this stage, cells in the barrier became elongated parallel to the long axis of the rudiment and overlapped. With further cell hypertrophy, the perichondrium consolidated and by stage 31 a distinct, compact structure, several cells thick and exhibiting cell-cell contacts had formed around the hypertrophic cell region. By stage 32, overlapping perichondrial cells could be seen surrounding the flattened cell region and this structure consolidated as cell hypertrophy spread from the centre towards the ends of the rudiment. The rounded cell zone at the epiphyses never formed a distinct perichondrium during the time course of this study. This differential structure of a compact perichondrium surrounding the hypertrophic cell region, a loose perichondrium surrounding the rounded cell region and an intermediate perichondrium surrounding the flattened cell region may facilitate the morphogenesis of the rudiment by acting as a constraining sheath restricting radial expansion but favouring longitudinal expansion.

Animals

Randomized trial of Codetron for pain control in osteoarthritis of the hip/knee.

Patients suffering from pain due to osteoarthritis of the hip and knee participated in a double-blind placebo controlled trial using daily Codetron home care units for 6 weeks over the tibial, saphenous, popliteal and sciatic nerves, and tender points. Seventy-four percent of patients in the real Codetron (Group A) and 28% of the patients in sham Codetron (Group B) improved their pain level more than 25% as measured by visual analogue scale. The difference in pain improvement in the two groups was statistically significant (p less than 0.02 using Fisher's exact probability ratio). Other functional parameters proved to be insensitive to change in this study. This is highly suggestive of beneficial effect of nonhabituating Codetron as a complementary modality in the therapy of chronic pain conditions such as osteoarthritis.

Adult

Cartilage morphogenesis in vitro.

The morphogenetic capacity of prechondrogenic mesenchyme from two developmentally distinct sources was investigated in high density micromass cultures. We confirmed an earlier report (Weiss & Moscona, 1958) that scleral mesenchyme formed cartilage sheets whilst limb bud mesenchyme formed distinct cartilage nodules. It was thus suggested by these authors that this morphogenesis was tissue type specific. However, by varying cell density at inoculation (which controls cell configuration) and by varying the relative amount of prechondrogenic mesenchyme present in cultures we found that dramatic changes in morphogenesis could be brought about. Viewed in these terms we suggest that cartilage morphogenesis in vitro is dependent on cell configuration and the presence of non-chondrogenic cell types and hence is not necessarily a function of an intrinsic morphogenetic potential of the constituent cells.

Animals