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Biomedical subjects

P Harrison

Publications and source records attributed to P Harrison.

At least 109 records · Page 6Linked to original sources
PubMed1996

In vivo muscle protein synthesis rates in the American lobster Homarus americanus during the moult cycle and in response to 20-hydroxyecdysone

Simultaneous measurements of in vivo rates of protein synthesis (Ks) in claw, leg and abdominal muscles were made in the American lobster Homarus americanus at three stages of the moult cycle. Ks values are significantly elevated during the premoult (stage D2-D3) and fall during the intermoult (stage C4) periods in all three muscles. Postmoult (stage A/B) levels are not significantly elevated above intermoult levels. Intermoult levels are between 0.3 and 0.4 % protein synthesized per day. In the premoult animals, the ribosomal activity (milligrams protein synthesized per microgram RNA per day) of the claw, abdominal and leg muscles is elevated three- to fivefold. The claw muscle maintains an elevated ribosomal activity into the postmoult stage whereas, by this stage, that of the other muscle tissues has fallen to intermoult levels. The RNA/protein ratios of the three muscle groups from intermoult, premoult and postmoult animals do not show any significant differences. 18S ribosomal RNA levels fluctuate slightly, with no consistent pattern over the moult cycle. In vivo injection of premoult concentrations of 20-hydroxyecdysone (20-HE) into intermoult lobsters results in elevated Ks values and ribosomal activity for the muscles after 3 days. RNA/protein ratios remain constant in the muscles in response to injections of 20-HE in vivo. In vitro preparations of leg muscle treated with 20-HE did not show similar elevated rates of protein synthesis.

Journal Article↗
PubMed1996

Spontaneous graft-versus-host disease following autologous peripheral blood progenitor cell transplantation in chronic myeloid leukaemia.

Myeloablation followed by haemopoietic reconstitution using autologous peripheral blood progenitor cells (PBPC) is applicable to some patients with CML, particularly where there is no allogeneic stem cell donor available, and interferon alpha has failed to achieve a significant cytogenetic response. Cells lacking the Philadelphia (Ph) chromosome can be collected at the early phase of myeloid recovery after intensive chemotherapy, and reconstitution after autografting can be associated with prolonged suppression of the Ph positive clone. It is possible that mechanisms other than this "in vivo purge' may contribute to disease control, for example an autologous graft-versus-leukaemia effect. We report two patients in whom significant autologous graft-versus-host disease (auto-GVHD) has occurred, which has not previously been described as a spontaneous event after PBPC autograft for CML. We postulate that mononuclear cells collected in an early phase of recovery after intense myelosuppression have the capacity to produce self-reactivity after autografting. These cells, which may include autoreactive T lymphocytes or antigen-presenting dendritic cells, might mediate a useful graft-versus-leukaemia effect.

Adult↗
PubMed1996

Inhibition of the acute-phase response in vivo by anti-gp130 monoclonal antibodies.

The acute-phase response is believed to be an important systemic defence reaction to inflammation during infection, trauma, injury or neoplasia. Although the interleukin-6 (IL-6) family of cytokines appear to be the major regulators of the acute-phase reaction, the exact biological significance of this process remains unknown. In this study, a panel of monoclonal antibodies (Mabs) was raised against the extracellular domain of human gp130 (the common signal transducing chain of the IL-6 cytokine family) in order to inhibit the biological activity of IL-6-like cytokines in vivo. Mabs designated 4B11 and 2H4 were most effective in the inhibition of the in vitro acute-phase response on hepatoma cells and prevented the IL-6-induced growth inhibition of A375 cells. Administration of the antibodies to dogs at a dosage of 8 mg/kg/d showed that 2H4 was a potent inhibitor of the IL-6-induced (40 micrograms/kg/d) acute-phase response, abrogating IL-6-mediated increments in fibrinogen, C-reactive protein and the platelet count. This antibody, the first described to abrogate the acute-phase response in vivo, may not only permit development of a new anti-inflammatory strategy, but provides an excellent tool for defining the function of acute-phase proteins in inflammation and infection.

Acute-Phase Reaction↗
PubMed1995

Laboratory medicine needs higher profile with medical students, MDs, pathologists say.

Laboratory medicine is a troubled specialty these days, buffeted by the conflicting pressures of reduced funding for more work and a declining physician population. A consortium of laboratory physicians has produced a report on the future of pathology and laboratory medicine, which explores the problems facing the specialties and some potential solutions. Raising the profile of laboratory medicine among medical students and eventual unification of pathology and the various arms of laboratory medicine are among the suggested solutions.

Canada↗
PubMed1995

Differential regulation of von Willebrand factor exocytosis and prostacyclin synthesis in electropermeabilized endothelial cell monolayers.

We have developed a system to permeabilize human umbilical vein endothelial cells in monolayer culture by application of a high-voltage electric field. The permeabilized preparation allows access of small molecules (M(r) < 1000) without loss of large cytosolic proteins. Electropermeabilized cells exocytose highly multimeric von Willebrand factor from secretory granules in response to added Ca2+ (EC50 = 0.8 +/- 0.02 microM), with levels comparable with those observed on stimulation of intact endothelial cells by physiological agonists. MgATP2- potentiates Ca(2+)-driven von Willebrand factor secretion. Other nucleoside triphosphates, but not non-hydrolysable analogues, can replace ATP. Electropermeabilized cells also synthesize and release prostacyclin in response to added Ca2+ (EC50 = 0.3 +/- 0.08 microM), but nucleoside triphosphates markedly inhibit, whereas nonhydrolysable GTP analogues increase, Ca(2+)-driven prostacyclin synthesis. We conclude that elevation of the intracellular [Ca2+] is sufficient to cause efficient exocytosis of von Willebrand factor from permeabilized cells, despite evidence that additional second messengers are needed in intact cells. We find no evidence in endothelial cells for a guanine nucleotide-binding protein promoting exocytosis, although one is clearly involved in stimulating Ca(2+)-driven prostacyclin synthesis.

Calcium↗
PubMed1995

Barer and Stoddart revisit the issue of funding academic health centres.

Four years after Drs. Morris Barer and Greg Stoddart presented their landmark report, Toward Integrated Medical Resource Policies for Canada, to the country's deputy ministers of health, not much progress has been reported on the reformation of Canada's academic health centres. A recent survey of respondents consulted for the original report showed "a deafening lack of responses" that indicated the situation has improved since the report was issued. Government respondents had a more positive opinion than administrators of the centres.

Academic Medical Centers↗
PubMed1995

The relationship between plasma and brain quinolinic acid levels and the severity of hepatic encephalopathy.

BACKGROUND/AIMS: Quinolinic acid is an endogenous neuroexcitant derived from tryptophan. Brain quinolinic acid concentrations are reportedly elevated in chronic liver failure. The aim of this study was to determine if brain quinolinic acid levels correlate with the severity of hepatic encephalopathy. METHODS: Postmortem samples of selected brain regions and plasma samples taken at several stages of encephalopathy were obtained from patients with acute and chronic liver failure. Quinolinic acid levels were measured by mass spectroscopy using [18O]quinolinic acid. RESULTS: Plasma quinolinic acid levels were significantly increased by stage I encephalopathy in patients with acute liver failure and by stages II and III in patients with chronic liver failure. Brain quinolinic acid levels were elevated only in patients with acute liver failure and were uniformly distributed at concentrations below those observed in plasma. CONCLUSIONS: The uniform distribution of quinolinic acid at subplasma concentrations in the brains of patients with acute liver failure suggests that it is synthesized peripherally and enters the brain across a permeabilized blood-brain barrier. Whereas the elevation of brain quinolinic acid levels in patients who died of acute but not chronic liver failure suggests that the involvement of quinolinic acid in the pathogenesis of hepatic encephalopathy is minimal, it could predispose these patients to seizures.

Acute Disease↗
PubMed1995

Perforation and partial obstruction of an armored endotracheal tube.

Armored endotracheal tubes are often used during cases in which there is a risk of compromise of a polyvinylchloride tube with positioning of a patient's head. The authors describe a case in which partial airway obstruction and perforation of such a tube occurred as a result of biting by a patient. Ways to avoid this complication are discussed.

Adult↗
PubMed1995

Serotonin immunoreactivity in the ventral nerve cord of the primitive crustacean Anaspides tasmaniae closely resembles that of crayfish

Syncarid crustaceans, of which only a few living species remain, have articulated segments with well-developed appendages along the length of the body, an arrangement thought to resemble that of the earliest malacostracan crustaceans. Decapod malacostracans have fused thoracic segments and reduced abdominal appendages. Modern representatives of the two groups are separated by at least 300 million years of evolutionary history. The serotonin immunoreactivity of ganglia and connectives from the ventral nerve cord of the syncarid Anaspides tasmaniae was compared with that of serially homologous ganglia of the crayfish Cherax destructor. Both species show the serotonin-immunoreactive longitudinal fibre bundles described from other decapods and thought to be part of a neuromodulatory network. They also have in common a number of the cell bodies associated with this system. Each species has some serotonergic cells in the region examined that are not present, or that do not stain, in the other species.

Journal Article↗
PubMed1995

Treatment of HL60 cells with various combinations of retinoids and 1 alpha,25 dihydroxyvitamin D3 results in differentiation towards neutrophils or monocytes or a failure to differentiate and apoptosis.

It is well documented that treatment of serum-grown HL60 cells with 10(-7) M all-trans retinoic acid (all-trans RA) induces neutrophil differentiation, whereas treatment with 10(-7) M 1 alpha,25 dihydroxyvitamin D3(D3) induces differentiation towards monocytes. In recent investigations, using serum-free grown HL60 cells, we observed that all-trans RA, at 10(-7) M, did not induce neutrophil differentiation and that all-trans RA, at 10(-8) M, reduced the D3 concentration required for monocyte differentiation to 5 x 10(-9) M. In this study, co-operative interactions between all-trans and 9-cis RA and D3 which promote neutrophil and monocyte differentiation of HL60 cells have been analysed in detail. Treatment of serum-free grown HL60 cells with 5 x 10(-7) M all-trans RA or 9-cis RA resulted in sub-optimal neutrophil differentiation (up to 25% mature cells). As shown for all-trans RA, 9-cis RA cooperated with D3 to promote monocyte differentiation. Culture of HL60 cells in 5 x 10(-7) M 9-cis RA together with a wide range of concentrations of D3 resulted in promotion of neutrophil differentiation at 10(-15)-10(-12) D3, a failure to differentiate and apoptosis at 10(-11)-10(-10) M D3, followed by co-operativity between 9-cis RA and 5 x 10(-9) M D3 in inducing monocyte differentiation in the absence of neutrophil differentiation. Similar results were obtained when HL60 cells were treated with 5 x 10(-7) all-trans RA together with a wide range of concentrations of D3. Cross titration analyses of the effects of 9-cis RA and D3 on HL60 cell differentiation were undertaken to determine the boundaries of the concentrations of each agent, alone and in combination, that give rise to optimal neutrophil and monocyte differentiation of HL60 cells. The observed cooperativities between either 9-cis RA or all-trans RA and D3 have important implications for the use of combinations of these agents in differentiation therapy.

Apoptosis↗
PubMed1995

BIII 277 CL is a potent and specific ion-channel blocker of the NMDA receptor-channel complex.

We determined the ability of a new benzomorphan derivative [2R-[2 alpha, 3(R*),6 alpha]]-1,2,3,4,5,6-hexahydro-3-(2-methoxypropyl)- 6,11,11-trimethyl-2,6-methano-3-benzazocin-9-ol hydrochloride (BIII 277 CL) to inhibit the N-methyl-D-aspartic acid (NMDA) receptor-channel complex in vitro and in vivo. BIII 277 CL potently displaced [3H]MK-801 binding from the NMDA receptor-channel complex in synaptosomal membrane preparations from rat brain cortex (Ki = 4.49 nmol/l). It was much less effective at displacing [3H]dihydromorphine, [3H]naloxone and [3H]ditolyguanidine binding in similar membrane preparations: the Ki values were 3323, 8031 and 1017 nmol/l, respectively. BIII 277 CL did not exhibit any marked affinities for a variety of other central neurotransmitter receptors. BIII 277 CL antagonized NMDA-induced [3H]noradrenaline release (EC50 = 1.7 mumol/l) and NMDA-induced inhibition of protein synthesis in rat hippocampal slices (EC50 = 3.0 mumol/l). In mice, BIII 277 CL prevented NMDA-induced lethality (ID50 = 0.54 mg/kg s.c.) and, as expected, also caused disturbances in motor coordination in the same dose range (ED50 = 0.47 mg/kg s.c.). The duration of BIII 277 CL was much shorter than than of (+)MK-801 in both tests. Finally, BIII 277 CL (0.3 mg/kg s.c. 5 times over 24 h) reduced the cortical infarct area in mice that had been subjected previously to focal cerebral ischemia by unilateral occlusion of the middle cerebral artery. In summary, these results indicate that BIII 277 CL is a potent and specific ion-channel blocker of the NMDA receptor-channel complex which could be used for the treatment of acute thromboembolic stroke in humans.

Animals↗