Search PubMedSearch

Biomedical subjects

D Morrison

Publications and source records attributed to D Morrison.

At least 19 recordsLinked to original sources

Raf functions downstream of Ras1 in the Sevenless signal transduction pathway.

Specification of the R7 cell fate in the developing Drosophila eye requires activation of the Sevenless (Sev) receptor tyrosine kinase, located on the surface of the R7 precursor cell, by its interaction with the Boss protein, expressed on the surface of the neighbouring R8 cell. Four genes that participate in the intracellular transmission of this signal have so far been identified and molecularly characterized: Ras1, Sos, Gap1 and sina (refs 4-8). The Drosophila homologue of the mammalian Raf-1 serine/threonine kinase, which has been implicated in signal transduction pathways activated by many receptor tyrosine kinases (reviewed in refs 9 and 10), is encoded by the raf locus (also known as l(1)polehole, Draf-1 or Draf). Here we show that the Drosophila Raf serine/threonine kinase also plays a crucial role in the R7 pathway: the response to Sev activity is dependent on raf function, and a constitutively activated Raf protein can induce R7 cell development in the absence of sev function. We also present genetic evidence suggesting that Raf acts downstream of Ras1 and upstream of Sina in this signal transduction cascade.

Animals

Responses of mucus-producing cells in gill disease of rainbow trout (Oncorhynchus mykiss).

This paper documents the responses of mucus-producing cells in the gills of rainbow trout (Oncorhynchus mykiss) throughout a naturally occurring outbreak of bacterial gill disease (BGD) and following exposure to experimentally induced high concentrations of ammonia and suspended solids. The responses were examined at three sites on the gill filament with three histochemical stains selected to identify the main types of mucous glycoproteins; these were periodic acid-Schiff (PAS), alcian blue pH 2.5 (AB2) and alcian blue pH 1.0 (AB1). In the BGD-infected fish, there was an increase in the numbers of PAS-positive and AB2-positive mucous cells and a corresponding decrease in AB1-positive cells. The greatest increase in mucus-producing cells occurred at the tips of the filaments, but the greatest relative change occurred at the mid-filamental (inter-lamellar) position. Fish exposed to high ammonia concentrations also had elevated numbers of mucus-producing cells, but there was no statistically significant change in fish exposed to high amounts of kaolin. The possible implications of these findings are discussed.

Ammonia

Stomatococcus mucilaginosus: an emerging pathogen in neutropenic patients.

Stomatococcus mucilaginosus was isolated from eight neutropenic patients during nine febrile episodes over a 13-month period. Five of these isolates were from definite infections, including one case of fatal meningitis. This slime-producing, catalase-variable, gram-positive coccus is a component of the normal oral flora of humans. Its biochemical profile may result in misidentification; however, unlike most micrococci, it characteristically fails to grow on media containing 5% NaCl. All but one of our isolates were sensitive to benzylpenicillin, and all were sensitive to vancomycin. S. mucilaginosus may prove to be an important pathogen in severely immunocompromised patients.

Adult

Bone turnover during short course prednisolone treatment in patients with chronic obstructive airways disease.

BACKGROUND: Although osteoporosis is a well known side effect of long term prednisolone, the effects of a short course are less clear. Biochemical markers of bone turnover were therefore studied in 10 men with chronic obstructive airways disease who required assessment of "steroid reversibility" (mean age 65 years, mean FEV1 1.2 1). METHOD: Patients received, single blind, two weeks of placebo, four weeks of prednisolone 20 mg/day, and then two further weeks of placebo. RESULTS: The mean (SD) fasting urinary hydroxyproline:creatinine ratio, a marker of bone resorption, increased by 65% with prednisolone (from 8.9 (5.7) to 14.7 (8.5) mumol/mmol) and returned to baseline after placebo. Serum alkaline phosphatase, a marker of net bone formation, fell after prednisolone by 28% (from 113 (41) to 81 (30) IU/1). Substantial changes occurred after only two weeks of prednisolone. Serum osteocalcin, calcium, and phosphate concentrations did not change significantly. CONCLUSIONS: Short courses of prednisolone increased bone resorption and inhibited bone formation after two and four weeks.

Aged

Cancer promotion in a mouse-skin model by a 60-Hz magnetic field: II. Tumor development and immune response.

This paper describes preliminary findings on the influence of 60-Hz (2-mT) magnetic fields on tumor promotion and co-promotion in the skins of mice. The effect of magnetic fields on natural killer (NK) cell activity in spleen and blood was also examined. Groups of 32 juvenile female mice were exposed to the magnetic field as described in part I. The dorsal skin of all animals was treated with a subthreshold dose of the carcinogen 7,12-dimethyl-benz(a)anthracene (DMBA). One week after the treatment, two groups were sham exposed (group A) or field exposed at 2 mT (group B) 6 h/day for 21 weeks, to test whether the field would act as a tumor promoter. No tumors developed in these two groups of mice. To test whether the magnetic field would modify tumor development by directly affecting tumor growth or by suppressing immune surveillance, two additional groups of mice were treated weekly with the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) and then either sham exposed (group C) or field exposed (group D). The time to appearance of tumors was shorter (but not statistically so) in the group exposed to magnetic fields and TPA. Some differences in NK cell activity and spleen size were observed between the sham- and field-exposed groups.

9,10-Dimethyl-1,2-benzanthracene

Language and gesture in late talkers: a 1-year follow-up.

A 1-year follow-up of relationships between language and symbolic gesture in 10 children with delayed onset of early lexical skills (Thal & Bates, 1988a) is reported. Original data are reevaluated in light of new knowledge about which late talkers continued to be significantly delayed 1 year later (truly delayed) and which ones had "caught up" (late bloomers). Results showed that all 4 children who were truly delayed at follow-up had been delayed in language comprehension at the first visit, but the 6 late bloomers had been at the same level as their age-matched controls. In addition, truly delayed late talkers had been significantly poorer on all of the gesture tasks than late talkers who caught up.

Child, Preschool

N-acetylmuramic acid inhibits spore germination and germination enzymes.

This report describes the inhibition of spore germination by N-acetylmuramic acid. At concentrations of 20 mM and higher, the rate of germination of the treated spores was ten-fold lower than that of the control spores. The inhibitor also depressed the activity of two germination-related enzymes; a coat-associated hexosaminidase and a core enzyme. These findings suggests that N-acetylmuramic acid affects spore germination by inhibition of the corticolytic enzymes. The results are discussed with respect to the possible role of these enzymes in germination.

Bacillus cereus

Clinical profile of remoxipride--a combined analysis of a comparative double-blind multicentre trial programme.

Nine double-blind studies comparing remoxipride to haloperidol in the treatment of acute schizophrenia formed the basis of this analysis. All studies followed a basic protocol with the main assessments performed regularly during the 4-6 week trial period according to the same methodology, thus allowing the data to be pooled. The results showed that remoxipride in a daily dose of 150-600 mg had a therapeutic effect comparable to that of haloperidol (5-45 mg/day), both on positive and negative symptoms. There was a clear advantage for remoxipride over haloperidol with regard to adverse events/symptoms, particularly extrapyramidal symptoms, but also drowsiness/somnolence and tiredness/fatigue. Anticholinergic drugs were used consistently less frequently as concomitant medication to alleviate extrapyramidal symptoms in the remoxipride group: the use of sedatives/hypnotics was approximately the same in both groups. Based on these and supportive clinical data, remoxipride seems to have a clinical profile characterized by antipsychotic efficacy in acute schizophrenia, apparently equal to that of haloperidol, and good tolerability in being non-sedative (in terms of drowsiness/somnolence) and with low incidences of extrapyramidal, autonomic, and endocrine symptoms.

Adolescent

Safety evaluation in both short- and long-term treatment of schizophrenia with remoxipride.

Results for laboratory and cardiovascular variables in both short-term (4-6 weeks) and long-term (greater than 6 weeks) double-blind studies in schizophrenic patients consistently showed comparably low incidences of both transient treatment-emergent changes and changes present at last rating for both remoxipride and haloperidol. The total incidence of serious adverse events in the short-term double-blind programme was approximately 2% for both remoxipride and haloperidol. The corresponding figure for remoxipride (n = 434) in long-term treatment was approximately 6%. Compared to those on haloperidol, fewer patients on remoxipride had trough plasma prolactin levels above the normal range in short-term treatment. The results with long-term treatment with remoxipride were similar. Breast swelling and galactorrhoea were infrequent treatment-emergent side effects with either drug. It was impossible to evaluate menstrual disturbance in short-term studies but in long-term use the incidence of treatment-emergent menstrual disorder was low in remoxipride patients. Too few patients continued treatment with haloperidol for a comparative long-term evaluation. Overall, based on the information available at present, remoxipride appears to offer a high degree of safety in both short-term and long-term treatment of schizophrenia.

Adult

Solitary bronchial amyloid presenting with haemoptysis.

Pulmonary amyloidosis can be classified into tracheobronchial diffuse alveolar-septal and nodular parenchymal forms. Tracheobronchial amyloidosis can be further subdivided into diffuse and focal varieties. The latter is rare. We report a patient with a focal intrabronchial deposit of amyloid who presented with haemoptysis. The haemoptysis ceased following bronchoscopic removal of this deposit.

Aged

Toxoplasmic chorioretinitis and hepatic granulomas.

A 71-yr-old male presented with a 2-month history of fever, malaise, and weight loss. Physical exam revealed chorioretinitis. Laboratory studies were notable for elevated levels of alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate transaminase, and alanine transaminase. Immunoglobulin G antibody to Toxoplasma gondii was positive to a dilution of 1:4096, whereas serologic studies for hepatitis A virus, hepatitis B virus, cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, Brucella, and Tularemia were negative. A percutaneous biopsy of the liver revealed hepatic granulomas. Culture of the biopsy specimen was negative for growth of mycobacteria or fungi. Spontaneous improvement in clinical and laboratory parameters occurred over a 4-month period.

Aged

The colony stimulating factor-1 receptor associates with and activates phosphatidylinositol-3 kinase.

Colony stimulating factor-1 (CSF-1) is a lineage-specific growth factor required for proliferation and survival of mononuclear phagocytes and their precursors. The CSF-1 receptor belongs to a family of ligand-activated protein-tyrosine kinases. Activation of the platelet-derived growth factor receptor, but not the CSF-1 receptor, leads to an increase in phospholipase C activity and a subsequent elevation in intracellular calcium. Recent studies have shown that a novel phosphoinositol (PtdIns) kinase, termed PtdIns-3 kinase, is stimulated by the platelet-derived growth factor receptor and certain oncogenes in the protein-tyrosine kinase family. PtdIns-3 kinase phosphorylates the D-3 hydroxyl position of the inositol ring of PtdIns, and its products do not participate in the generation of the second messenger inositol 1,4,5-trisphosphate (Ins(1,4,5)P3). Here we report that addition of CSF-1 is followed by activation of PtdIns-3 kinase in a macrophage cell line (P388 D1), which contains CSF-1 receptors, and in BALB/c fibroblasts made to express the human CSF-1 receptor. Furthermore, we show that activation of the CSF-1 receptor results in the accumulation in intact cells of polyphosphoinositides phosphorylated at the D-3 position of the inositol ring. Thus activation of the CSF-1 receptor stimulates PtdIns-3 kinase activity, indicating a novel pathway for CSF-1 receptor-mediated signal transduction.

Animals