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Biomedical subjects

J M Thomas

Publications and source records attributed to J M Thomas.

At least 307 records · Page 17Linked to original sources
PubMed1986

Agonist-induced down-regulation of muscarinic cholinergic and alpha 2-adrenergic receptors after inactivation of Ni by pertussis toxin.

Desensitization of the responsiveness to hormones or drugs is often mediated by down-regulation of receptors. The stimulatory coupling protein (Ns) of adenylate cyclase has been shown to be involved in the down-regulation of stimulatory beta-adrenergic receptors. Whether the inhibitory coupling protein (Ni) is involved in the down-regulation of receptors that inhibit adenylate cyclase is not known. We wished to determine whether down-regulation of inhibitory muscarinic cholinergic and alpha 2-adrenergic receptors occurs in neuroblastoma X glioma hybrid cells after the ability of Ni to inhibit adenylate cyclase is inactivated by pertussis toxin. After treatment of cells with pertussis toxin, the ability of carbachol or epinephrine to inhibit prostaglandin E1-stimulated cAMP accumulation in intact cells was either completely prevented or markedly attenuated, respectively, indicating functional inactivation of Ni. Furthermore, pertussis toxin treatment of membrane fragments from these cells did not result in labeling of the 41,000-dalton alpha-subunit of Ni with ADP ribose from [32P] NAD, indicating maximal ADP ribosylation of Ni by prior treatment of cells with pertussis toxin. Carbachol treatment of cells resulted in down-regulation of muscarinic cholinergic receptors to 45.7 +/- 12.5% and 52.5 +/- 13.5% of control values for toxin-untreated and toxin-treated cells, respectively. Epinephrine treatment of cells caused homologous desensitization of alpha 2-receptor-mediated inhibition of cAMP accumulation and down-regulation of alpha 2-adrenergic receptors to 42.9 +/- 11.4% and 53.2 +/- 5.3% of control values for toxin-untreated and toxin-treated cells, respectively. Down-regulation of muscarinic cholinergic receptors by carbachol and of alpha 2-adrenergic receptors by epinephrine was not due to the effect of retained agonist and was agonist specific, since it could be prevented by the antagonists atropine and yohimbine, respectively. We conclude that agonist-mediated down-regulation of both the muscarinic cholinergic receptor and the alpha 2-adrenergic receptor does not require functional inhibitory coupling.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Muscarinic cholinergic receptor-induced enhancement of PGE1-stimulated cAMP accumulation in neuroblastoma X glioma cells: prevention by pertussis toxin.

Chronic treatment of neuroblastoma X glioma hybrid cells (NG 108-15) with the muscarinic cholinergic agonist carbachol, which acutely inhibits adenylate cyclase, resulted in a 104 +/- 10% increase in PGE1-stimulated cAMP accumulation. Pretreatment of intact cells with pertussis toxin can structurally modify the inhibitory regulatory protein, Gi, by ADP-ribosylation and thus abolish the acute inhibition by carbachol. Pretreatment of the cells with pertussis toxin also resulted in a 27 +/- 8% increase in PGE1-stimulated cAMP accumulation. In the pertussis toxin-treated cells, chronic treatment with carbachol did not further enhance the PGE1 stimulation. These results suggest that functional Gi is required for the development of muscarinic cholinergic-induced enhancement of PGE1-stimulated cAMP accumulation.

Adenosine Diphosphate Ribose↗
PubMed1986

Neutrophil chemotaxis in rhesus macaques (Macaca mulatta).

Chemotactic responses of isolated peripheral blood neutrophils from rhesus macaques (Macaca mulatta) were studied, using a micropore filter method. Cell migration toward zymosan-activated serum was similar to that of human cells, whereas the response to N-formyl methionyl leucyl phenylalanine (FMLP) was weaker than was that in human cells, requiring higher concentrations of FMLP for maximal migration. Optimal FMLP concentrations for attraction of rhesus neutrophils and human neutrophils were 5.0 X 10(-7)M and 1.0 X 10(-8)M, respectively. The chemotactic responses of the 2 neutrophils to complement (zymosan-activated serum) were similar. However, rhesus neutrophils required a higher concentration of the formyl peptide, FMLP, for maximal migratory response.

Animals↗
PubMed1985

The role of greater omentum in reconstructing skin and soft tissue defects of the groin and axilla.

In three patients undergoing extended inguinal (2) or axillary (1) block dissection for recurrent malignant disease use of conventional reconstructive methods was not possible. Transposed greater omentum was used to provide a vascularized base for split-thickness skin grafts in two patients and to protect a vascular prosthesis placed in heavily irradiated tissues in the third. In each case whole limb ablation was avoided and the salvaged limb showed good function. No local recurrence of malignant disease was seen.

Aged↗
PubMed1985

Heart size in high-kilovoltage chest radiography.

High-kilovoltage (kV) radiography of the chest using an air gap results in magnification of the heart and thorax despite the use of a longer focus-to-film distance. One hundred patients had their recent high-kV chest radiograph compared with their previous low-kV film. There was a significant increase in all cardiac parameters. Geometric distortion of the cardiac shadow also occurred, resulting in magnification and elongation preferentially affecting the left side of the heart. We believe this causes an additional subjective impression of a large heart. Radiologists and clinicians should revalue their assessment of cardiac size when such a technique is used.

Heart↗
PubMed1985

Hyperparathyroidism--patterns of presentation, symptoms and response to operation.

Forty-three patients operated upon for hyperparathyroidism over a 7-year period are reviewed with reference to modes of presentation, symptoms and symptomatic response following operation (76% of symptoms cured or improved). The patterns of presentation are discussed in relation to the increasing use of routine biochemical screening; emphasis is given to the symptoms admitted by 17 so-called 'asymptomatic' patients diagnosed in this way and to their improvement following surgery (75% of symptoms). Symptomatic improvement among a similar group of seventeen 'asymptomatic' patients undergoing operations for thyroid swellings was observed in only 9% of symptoms. In the light of such subjective improvement following parathyroidectomy, the theoretical prophylactic benefit of operation and its lack of morbidity, an aggressive surgical approach to the disease is considered justified.

Adult↗
PubMed1984

Evidence for a two-step process in prostaglandin secretion. Intracellular accumulation of prostacyclin precedes its release from human endothelial cells in culture.

Cultured endothelial cells (EC) from human umbilical vein were incubated with [U-14C]arachidonic acid (AA) followed by a challenge with thrombin (2 units/ml) or calcium ionophore A23187 (5 microM) for 0.5-10 min at 37 degrees C. In both cases, AA was rapidly liberated from phospholipids and converted into prostaglandin I2 (PGI2), as determined by the radioactivity of the stable derivative 6-keto-PGF1 alpha. Maximal liberation of AA and synthesis of PGI2 were achieved within 2 min, but the two compounds first accumulated in EC prior to their release into supernatants. This finding, which was never reported before, raises the question of the mechanism of AA and PG release through the cell membranes and offers a convenient model to investigate this still obscure process.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Sialic acid residues contribute to the heterogeneity of human serum ribonuclease: demonstration by isoelectric focusing and neuraminidase treatment of serum.

Ribonuclease (RNase) activity from human serum appears as multiple zones of activity following isoelectric focusing in thin layer polyacrylamide gel. At least one but not all of these zones is cross reactive with rabbit antibovine pancreatic RNase A antiserum. Treatment of serum or partially purified serum RNase with neuraminidase reduces the complexity of the serum RNase banding pattern to a major band which focuses at a pH of 9.5 or greater and a minor zone of activity which focuses at about pH 6.0-6.2. Trypsin does not affect the pattern. Thus, sialic acid residues account for a large portion of the heterogeneity of human serum RNase. Neuraminidase treatment is requisite for evaluating RNase from serum and certain other sources.

Animals↗
PubMed1984

Phosphatidylcholine is the major phospholipid providing arachidonic acid for prostacyclin synthesis in thrombin-stimulated human endothelial cells.

Upon incubation for 24 hours with [3H]arachidonic acid (AA, 1 mu Ci/ml), cultured endothelial cells from human umbilical vein incorporated one half of the added radioactivity, mostly into phospholipids (83% of the total cell radioactivity). Distribution of the label between the various phospholipid classes was found to reflect the distribution of endogenous AA. Stimulation with human thrombin (2 U/ml) promoted a rapid release of radioactive material into supernatants, which contained essentially 6-keto-prostaglandin F1 alpha and non-converted AA. This process levelled off at 10 min, at which time phosphatidylcholine displayed a decrease accounting for 3.7% of the total cell radioactivity. Phosphatidylinositol also appeared significantly diminished, but this decrease was almost 2.5 fold less than that observed in phosphatidylcholine. It is concluded that AA availability for prostacyclin biosynthesis is mostly regulated by a phospholipase A2.

Arachidonic Acids↗
PubMed1984

Concentration of orally administered and chronically fed 95mTc in Japanese quail eggs.

A chronic feeding study using 95mTc incorporated into alfalfa and an acute study where 95mTc was amended to alfalfa showed that about 8.4% of ingested Tc was transferred to eggs. After 10 days of chronic feeding, 80% of the Tc was in yolk, 20% in albumin and less than 1% in shell and associated membranes. At necropsy, technetium concentrations in the three largest oocytes were nearly equal. The biological half-time for Tc was about one to two days in acute studies. Results from the chronic feeding study also indicated that Tc levels in albumin reach a maximum between three and five days while maximum yolk concentration is attained in about six to seven days. Albumin concentrations declined about 20-50% after Day 6.

Administration, Oral↗