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Biomedical subjects

A Morgan

Publications and source records attributed to A Morgan.

At least 19 recordsLinked to original sources
PubMed1992

Interaction between protein kinase C and Exo1 (14-3-3 protein) and its relevance to exocytosis in permeabilized adrenal chromaffin cells.

The roles of protein kinase C (PKC) and Exo1 in exocytosis from digitonin-permeabilized adrenal chromaffin cells were explored by using exogenous purified proteins in a run-down/reconstitution system. The stimulatory action of Exo1 on exocytosis from run-down cells was found to be completely dependent on the continuous presence of exogenous MgATP, suggesting that it acts on the slow phase of exocytosis [Holz, Bittner, Peppers, Senter & Eberhard (1989), J. Biol. Chem. 264, 5412-5419]. Partially purified rat brain PKC was found to be able to stimulate Ca(2+)-dependent exocytosis from run-down cells in a dose-dependent manner. This effect was indeed due to PKC and not a contaminant in the PKC fraction, since the PKC activator phorbol 12-myristate 13-acetate (PMA), under conditions in which control secretion was not affected, potentiated the effect of the exogenous PKC in stimulating secretion. Furthermore, although either PKC or Exo1 alone could stimulate exocytosis from run-down cells, the effect of combining the fractions was synergistic, as had previously been observed using PMA treatment combined with Exo1 incubation [Morgan & Burgoyne (1992) Nature (London) 355, 833-836]. The observed synergy between PKC and Exo1 was not due to PKC-mediated phosphorylation of Exo1, and Exo1 was found not to affect PKC activity in enzyme assays. We conclude that PKC and Exo1 act synergistically in the slow phase of Ca(2+)-dependent exocytosis from adrenal chromaffin cells. Furthermore, PKC does not directly affect Exo1, but rather enhances the activity of Exo1 by a putative phosphorylation of another, unidentified, component of the exocytotic machinery which facilitates the action of Exo1 in exocytosis.

14-3-3 Proteins↗
PubMed1992

Exo1 and Exo2 proteins stimulate calcium-dependent exocytosis in permeabilized adrenal chromaffin cells.

In many cell types an increase in cytosolic calcium is the main signal for the exocytotic release of stored secretory components such as hormones and neurotransmitters. The site of action of calcium in exocytosis is not known, neither are the participating molecules. In the case of the intracellular membrane fusions that occur during transport through early stages of the secretory pathway, several cytosolic and peripheral membrane proteins are necessary. Permeabilized cells have been useful in understanding the requirements for calcium and nucleotides in regulated exocytosis and under certain conditions there is leakage of soluble protein components and run-down of the exocytotic response. This system can be used to identify the soluble proteins involved in exocytosis, one candidate in chromaffin cells being annexin II (calpactin). Here we use this assay to identify two other cytosolic protein factors that regulate exocytosis in permeabilized adrenal chromaffin cells, which we term Exo1 and Exo2. Exo1 from brain cytosol resolves on electrophoresis in SDS-polyacrylamide gels as a group of polypeptides of relative molecular mass approximately 30,000 and shares sequence homology with the 14-3-3 family of proteins. The ability of Exo1 to reactivate exocytosis is potentiated by protein kinase C activation and therefore Exo1 may influence the protein kinase C-mediated control of Ca(2+)-dependent exocytosis.

14-3-3 Proteins↗
PubMed1992

Transcriptional expression of the viral genome in the Epstein-Barr virus-induced tamarin lymphoma and the corresponding lymphoblastoid tumour lines.

Inoculation of the cottontop tamarin with Epstein-Barr virus (EBV) invariably gives rise to mono- or oligoclonal large cell lymphoma occurring at multiple sites, and which resembles to a certain extent B cell lymphoma that occurs in the immunodeficient patient. The viral transcriptional pattern in tamarin tumour biopsies and in the corresponding tumour cell lines was investigated by means of the synthesis of radioactive single-stranded cDNA. It was found that the EBV transcripts came mainly from the fragments BamH1-H, BamH1-S, BamH1-A and EcoR1-Dhet. Transcripts from a few other early or late genes, namely BARF1, BSLF1/BMLF1, BBLF-4, BLLF1 and BXLF2, were also detected in one of the three biopsies tested. It would be important to characterize the transcripts that originate from the region where viral latent expression has not previously been observed. Our results also revealed that there is a sharp increase in EBV transcription in the tumour cell lines derived from the tamarin lymphomas. Simultaneously, the copy number of the viral genome was found to be amplified. Such a significant change in viral activity might be indicative of a close virus-host cell interaction in vivo.

Animals↗
PubMed1992

Estimates of embryonic and fetal doses from 239Pu.

Previously reported studies on the transfer of 238Pu from the maternal circulation to the developing embryo and fetus in rats and guinea pigs have provided data for developing dosimetric models. The highest concentrations of 238Pu were measured in the yolk sac. In late gestation, preferential uptake of 238Pu in liver and bone was observed. The data obtained, together with other published information, have been used to estimate in utero doses to hemopoietic tissues, taking account of transfer to the blastocyst/egg cylinder, yolk sac, liver, and bone marrow. From animal data, the concentration ratios relative to maternal liver for these tissues were taken to be 0.1, 2, 0.01, and 0.02, respectively, and were applied to periods of human gestation of 0-2.5 wk, 2.5-6 wk, 6-12 wk, and 12-38 wk, respectively. Doses to fetal tissues from 239Pu were calculated for chronic ingestion by the mother for a total of 1.8 kBq 239Pu during the year of pregnancy, giving a committed effective dose to the mother of 1 mSv. On this basis, the total in utero dose to hemopoietic tissue was about 2 microSv compared with red bone marrow doses of 34 microSv to the mother for the year. The yolk sac and bone marrow dominated in utero doses. The total dose to hemopoietic tissue in the offspring to age 70 y, taking into account the activity present at birth and including in utero doses, was estimated as 24 microSv compared with a maternal dose to red bone marrow of 2.5 mSv. An acute maternal intake of 1.8 kBq by ingestion during the period of yolk sac hemopoiesis would result in the highest in utero dose, estimated at about 36 microSv. However, activity at birth would be lower, giving only a small additional dose.

Animals↗
PubMed1992

Effects of inhaled alpha-emitting actinides on mouse alveolar macrophages.

The effects of inhaled alpha-emitting actinides on the alveolar macrophage (AM) population of the rodent lung are reviewed and, in particular, of the effects of 239PuO2 on murine AM. The effects discussed include changes the AM pool size, macrophage diameter, mobility, phagocytic competence, and enzyme content. Finally, similarities in the dose-response relationships for the induction of nuclear aberrations by alpha emitters and in the induction of lung tumors by the same materials are noted.

Actinoid Series Elements↗
PubMed1991

Surgical treatment and long-term neurodevelopmental outcome for infants with idiopathic aqueductal stenosis.

Evaluation of in utero shunting for fetal ventriculomegaly requires an analysis of the ex utero treatment of a comparison population of infants with idiopathic aqueductal stenosis (IAS). In this study, 14 neonates with IAS were followed with detailed developmental assessment profiles for 18 months or longer. Using magnetic resonance imaging, the preoperative and postoperative frontal cortical mantle widths (FCMW) were determined for each patient. Four of 14 children demonstrated normal outcomes while 5 of 14 children showed abnormal outcomes. The remaining 5 children demonstrated minimally impaired outcomes. No child with a postoperative FCMW below 30 mm showed normal development on any scale, while all children with abnormal development demonstrated a postoperative FCMW of 21 mm or less. In conclusion, the prognosis for normal long-term neurodevelopment in infants with IAS, despite prompt ex utero treatment, is guarded; the majority of such children will show developmental delays of varying degrees. The FCMW serves as a reasonable prognostic indicator in this patient population.

Cerebral Aqueduct↗
PubMed1991

The incorporation of plutonium by the embryo and fetus of rats and guinea-pigs.

The transfer of 238Pu from the maternal circulation to the developing embryo and fetus was studied in rats and guinea-pigs to provide data for the development of dosimetric models for the human embryo and fetus. Following administration at different stages of gestation, measurements were made after 3 days in the rat and 7 days in guinea-pigs. The amount transferred was greater after administration at later stages of gestation, up to a maximum of about 0.8-0.9% of the injected activity per fetoplacental unit (FPU) and about 0.2% per fetus in both species. In advanced gestation the yolk sac, the initial site of haemopoietic stem cells, contained up to 80% of the total activity in the FPU in rats, compared with about 25% for the guinea-pig; retention in placental trophoblast was greater in the guinea-pig. The concentrations of 238Pu in the yolk sac were generally about two to three orders of magnitude greater than fetal concentrations and of the same order as in maternal liver and bone. In both species, concentrations in the embryo and fetus were greatest after injection early in gestation, reached their lowest around mid-organogenesis and increased again in later gestation. The fetus:mother whole-body concentration ratios in late gestation were about 0.1 and 0.05 in rats and guinea-pigs, respectively. Measurements were also made of the 238Pu retention in neonates at birth. In guinea-pigs the liver accounted for about 6-9% of retained activity; similar values for femora indicated skeletal retention of about 60-80%. For administration at each stage of gestation, and particularly at early stages, transfer of 238Pu to the fetus continued throughout gestation but concentrations decreased due to fetal growth.

Animals↗
PubMed1991

Sites and efficacy of photodamage by tin etiopurpurin in vitro using different delivery systems.

Photosensitization by tin etiopurpurin (SnET2) was determined in cell culture using sensitizer dissolved in ethanol or solubilized via three different delivery systems: Cremophor EL, gamma-cyclodextrin or Molecusol (a more water-soluble cyclodextrin derivative). Sensitizer uptake was substantially more efficient when the delivery systems were employed, in terms of intracellular level needed to lethally photosensitize cells. We observed photodamage at both membrane and mitochondrial loci, but the former was better correlated with loss of viability.

Animals↗
PubMed1979

Estimation of myocardial infarct size in man using 99m Tc polyphosphate.

We have critically evaluated the use of 99m Tc polyphosphate to estimate myocardial infarct size. Optimum conditions were first defined with respect to infarct edge definition, and relative activity over infarct and bone and in blood pool. The scintigrams of 53 patients with acute transmural myocardial infarction were recorded under these defined constant conditions and analysed in various ways. Visual grading of infarct area or intensity correlated poorly with other indices of infarct severity. Computer-assisted measurements of above-background infarct uptake area or of total farct activity correlated well with clinical, electrocardiographic, and enzymatic measurements of infarct severity.

Adult↗
PubMed1979

The use of tienilic acid in nephrotic syndrome: a clinical study.

The diuretic and uricosuric activities of tienilic acid 250--50 mg daily over a minimum six week period have been studied in seven patients with the nephrotic syndrome secondary to glomerulonephritis proven by renal biopsy. Tienilic acid failed to control oedema in one patient who had to be withdrawn. In the six other patients a hypouricaemic effect with increased urate clearance was noted. No consistent effects were noted with respect to the serum cholesterol and triglyceride concentrations. No side effects were observed. It is concluded that in nephrotic patients tienilic acid behaves as a mild diuretic with consistent hypouricaemic and uricosuric effects.

Adolescent↗
PubMed1978

Lung water changes after thermal burns. An observational study.

Pulmonary extravascular water has been measured as lung thermal volume (LTV) in a group of nine burned patients. Transducer-detectable indicators were used to permit frequent repetition and quick results. Concurrent recordings were made of cardiac output, pulmonary capillary wedge pressure and the usual hemodynamic variables. Moderate elevation of LTV was seen in all, reaching a maximum value before peripheral edema formation was complete. Left heart filling pressures were low as plasma albumin concentration. Clinical pulmonary edema occurred in one patient treated mostly with crystalloid solution. In several, a secondary peak coincided with edema mobilization.

Adult↗
PubMed1978

Significance of fibre length in the clearance of asbestos fibres from the lung.

Rats were exposed by inhalation to radioactive anthophyllite asbestos. Animals were then killed serially over a period of 205 days and the fibre content of the lungs measured radiometrically. The lungs were subjected to selective bronchopulmonary lavage and the mean fibre content determined of free cells recovered from the alveolar spaces. The length distributions of fibres recovered from the lungs by lavage, and of those remaining in the lungs following lavage, were measured. Short (less than 5 micrometer) fibres are cleared from the lung via the conducting airways more efficiently than longer fibres and fibres exceeding 50 micrometer in length are not removed from the lungs by this route. Although fibres of about 200 micrometer in length were present in all the lungs examined, the longest which could be recovered by lavage, once fibre deposited in the airways had been cleared, was only about 100 micrometer decreasing to 60-70 micrometer after 205 days. It is suggested that long fibres are more liable than short to penetrate the alveolar wall as they tend to bridge the alveolar ducts and alveoli.

Animals↗