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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 361 records · Page 20Linked to original sources
PubMed1988

Clinical presentation and natural history of patients with essential thrombocythemia and the Philadelphia chromosome.

Six women presented with the clinical picture of essential thrombocythemia (ET) without the anemia, marked splenomegaly, and extreme leukocytosis characteristic of chronic myelogenous leukemia (CML). All had the Philadelphia chromosome on karyotype analysis of the bone marrow. Peripheral basophilia was present in four cases, providing a clinical clue that the Philadelphia chromosome might be present. Marrow biopsy showed granulocytic hyperplasia and either small megakaryocytes or sheets of megakaryocytes with marked atypia, findings that are more typical of CML than ET. The clinical importance of finding the Philadelphia chromosome in patients who seem to have ET is in assessing prognosis. ET generally follows a chronic, indolent course. However, five of these six patients who had the Philadelphia chromosome underwent clinical transition to the accelerated phase of CML or blastic leukemia in 4-7 years.

Adult↗
PubMed1988

Astrocytes as eicosanoid-producing cells.

A variety of prostaglandins and leukotrienes, together with thromboxane and prostacyclin metabolites, can be detected in central nervous tissues and in cerebrospinal fluid. Defined cultures of astrocytes have revealed these cells to be a major source of eicosanoids. In common with other eicosanoid-producing cells, agents such as calcium ionophores and phorbol esters are potent stimuli for promoting release. While in other tissues agonists for receptors linked to calcium mobilisation prompt eicosanoid release, this does not seem to be the case in astrocytes, though a range of such receptors are present. The notable exceptions to this observation are adenosine triphosphate and adenosine diphosphate, presumably acting through P2 purinergic receptors. Many cell types in the CNS are targets for eicosanoids, possessing receptors linked to adenylate cyclase or phospholipase C. An appreciation of the functional significance of activation of these receptors is just now beginning. Eicosanoids have effects in the CNS that involve not only the vascular supply but also synaptic modulation and immune regulation.

Animals↗
PubMed1988

Psychiatric disorder and illness behaviour in rheumatoid arthritis.

A detailed physical and psychiatric assessment of 80 patients with definite or classical rheumatoid arthritis was performed using diagnostic criteria for psychiatric disorder appropriate for those with physical illness. Seventeen (21%) patients had depression or anxiety severe enough to warrant treatment. The presence of pychiatric disorders was not related to the duration of the arthritis nor to 11 other indicators of its severity with the exception of grip strength (p less than 0.002) and Fries Functional grade (p less than 0.005). It was significantly related to the presence of social stress (p less than 0.05) and lack of social support (p less than 0.005). Those with psychiatric symptoms scored higher on an illness behaviour scale, indicating that they perceived their illness as very severe. These also worried excessively about it and failed to be reassured by the doctor. Such illness behaviour was displayed by some patients who had severe arthritis but lacked social support. In others the complaints were unfounded because their arthritis was mild. They also experienced much social stress and lacked social support. We conclude that psychiatric illness occurs in rheumatoid arthritis with similar frequency to that of other general medical patients. It is principally related to social stress and lack of support rather than severity of arthritis, and may lead to abnormal illness behaviour. Since lack of social support appears of prime importance in determining disability, its assessment is essential for the rehabilitation of the disabled patient with RA.

Adolescent↗
PubMed1988

Effects of extracellular potassium on glycogen stores of astrocytes in vitro.

Astrocyte-enriched and meningeal cell cultures of the rat cerebral cortex were prepared, and their glycogen content was measured after 10-90 min under control (2.5 mM) concentrations of potassium after prefeeding with 20 mM glucose. No net change in glycogen level was noted in either culture over this period. Cell cultures were then exposed to increased concentrations of potassium (5, 10, and 15 mM), and their glycogen content was measured after 10-90 min. Both types of cell culture showed complex and variable changes in glycogen content. In general, increased potassium concentrations caused astrocyte glycogen stores to be reduced at physiological increases of potassium levels (from 2.5 to 5 mM and above), although a period of resynthesis was evident at all potassium concentrations. Meningeal cell glycogen levels were highly variable and only affected by high (10 and 15 mM) levels of potassium. These results are discussed with respect to the theory that changes in the external potassium concentration caused by neuronal activity might act as a signal controlling astrocyte glycogen stores.

Animals↗
PubMed1988

Effects of neurotransmitters on astrocyte glycogen stores in vitro.

We have used receptor binding assays to determine the presence of three neurotransmitter receptors in a crude membrane fraction derived from neonatal rat cortical astrocyte cultures and subsequently determined the effects of transmitter receptor activation on astrocyte glycogen content in vitro. beta-Adrenergic (KD = 88 pM; Bmax = 51 fmol/mg of protein), serotonin (KD = 70 nM; Bmax = 44 pmol/mg of protein), and muscarinic cholinergic receptors (KD = 79 pM; Bmax = 44 fmol/mg of protein) were found to be present on astrocyte membranes using [3H]dihydroalprenolol, [3H]serotonin, and [3H]quinuclidinyl benzilate, respectively, as ligands. Astrocyte cultures exposed to noradrenaline but not specific alpha- and beta-receptor agonists contained 33% less glycogen than controls. Neither serotonin nor carbachol caused alterations in astrocyte glycogen content under normal conditions. Reserpine-treated cultures, however, responded to serotonin with a 28% decrease in glycogen content and contained higher levels of glycogen than non-reserpine-treated controls (a 55% increase). These results show that both noradrenaline and serotonin can evoke astrocyte glycogenolysis and that noradrenergic control of glycogen metabolism is probably exerted through both alpha- and beta-receptors. Neurotransmitter control of astrocyte glycogen turnover may represent a form of neuron-astrocyte signalling in addition to that provided by changes in external potassium concentration.

Animals↗
PubMed1988

Characteristics of phorbol ester- and agonist-induced down-regulation of astrocyte receptors coupled to inositol phospholipid metabolism.

We have examined some of the characteristics of phorbol ester- and agonist-induced down-regulation of astrocyte receptors coupled to phosphoinositide metabolism. Our results show that preincubation of [3H]inositol-labelled astrocyte cultures with phorbol 12-myristate 13-acetate (PMA) resulted in a time- (t 1/2, 1-2 min) and concentration-dependent (IC50, 1 nM) decrease in the accumulation of [3H]inositol phosphates (IP) evoked by muscarinic receptor stimulation. Much longer (30-40 min) preincubation periods with higher concentrations (IC50, 600 microM) were required to elicit the same effect with the receptor agonist carbachol. Following preincubation, agonist-stimulated [3H]IP accumulation recovered with time; in both cases pretreatment levels of inositol lipid metabolism were attained within 2 days. Both phorbol ester and agonist pretreatments were also effective in reversing the carbachol-evoked mobilisation of 45Ca2+ in these cells. However, their effects on phosphoinositide metabolism were found not to be additive. Although neither pretreatment affected the incorporation of [3H]inositol into phosphoinositides, both resulted in a loss of membrane muscarinic receptors as assessed by [3H]N-methylscopolamine binding. In washed membranes prepared from [3H]inositol-labelled cultures, the guanine nucleotide analogue, guanosine 5'-O-thiotriphosphate (GTP-gamma-S), caused a dose-dependent increase in [3H]IP formation. This response was enhanced when carbachol was also included in the incubation medium, although the agonist alone was without effect. Pretreatment with either PMA or carbachol had no effect on GTP-gamma-S-stimulated [3H]IP accumulation but did reduce the ability of carbachol to augment this response. Similar findings were obtained when membranes were exposed directly to PMA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Microdysgenesis in resected temporal neocortex: incidence and clinical significance in focal epilepsy.

Fifty patients underwent superficial temporal lobectomy for intractable temporal lobe epilepsy. Total cure rate was 52%, and significant improvement was achieved in 88%. Cytoarchitectural changes in gray and white tissue were analyzed under light microscopy. Neuronal dysgenesis was correlated with the duration of seizure disorder, age of onset, and other etiologic factors, and with clinical outcome. Temporal lobes from 33 neurologically normal autopsy brains which were age- and sex-matched with patients were examined as controls. Severe neuronal ectopia (greater than 8 neurons/2 mm2 white matter) was present in 42% of patients with epilepsy and in none of controls. There was neuronal clustering in 28% of those with epilepsy, and Chaslin's (subpial) gliosis in 38%. Controls did not have these changes. The presence of severe neuronal ectopia and clustering was predictive of a favorable clinical outcome following surgery (p less than 0.05). No correlation was found between microdysgenesis and other factors. These findings suggest that the presence of neuronal dysgenesis may be of significance in the clinical outcome following surgery, and that the abnormal tissue may be important as a morphologic substrate for seizures in some patients.

Adolescent↗
PubMed1988

Multiple agent chemotherapy (POACH) in previously treated and untreated patients with chronic lymphocytic leukemia.

A multiple agent chemotherapy protocol utilizing cyclophosphamide, adriamycin, cytosine-arabinoside, vincristine, and prednisone (POACH) was administered to 65 patients with chronic lymphocytic leukemia. Nineteen (56%) of the 34 previously untreated patients responded, with (21%) of the patients obtaining a complete remission. The response rate for the 31 previously treated patients was significantly lower, with 2 complete remissions and 6 partial remissions. The median survival of the untreated patients was 58 months, compared with 15 months for the previously treated group (p less than 0.01). In both groups, patients who achieved a complete or partial remission had a significantly longer survival than did patients who did not respond. The response rates for all sites of involvement were similar. Sixteen (47%) of 34 previously untreated patients and 9 of 31 (29%) previously treated patients returned to Rai stage 0. The survival of patients who returned to stage 0 was significantly superior to that of others in both groups. The overall mortality during the study was significantly higher for previously treated patients. Pretreatment Rai stage was strongly predictive of death on study. Rai and Binet stages were not strongly predictive of response or length of survival in untreated patients but stages were predictive for survival and in treated patients. The regimen was well tolerated, with infectious complications being the major morbidity. Patients who responded to POACH had a significantly longer survival than did those who did not, and further attempts to improve the complete and partial remission rates in chronic lymphocytic leukemia will be undertaken.

Adult↗
PubMed1987

The in vitro transcription of the 7SK RNA gene by RNA polymerase III is dependent only on the presence of an upstream promoter.

Deletion analysis was carried out on the human 7SK RNA gene to map regions essential for in vitro transcription by RNA polymerase III. The sequence promoting transcription is located between 37 and 3 bp upstream of the 7SK RNA coding region. RNA polymerase III transcription of adjacent plasmid sequences can be directed by this promoter in the complete absence of the 7SK RNA coding region, indicating that no internal promoter sequences are required. Transcription is terminated by a stretch of T residues, typical of RNA polymerase III transcription. The promoter contains a TATA box at position -25, mutations within which dramatically reduce the efficiency of transcription. Upstream sequences from position -37 to -243 increase the promoter's efficiency. The promoter recognized by RNA polymerase III is structurally and functionally similar to the promoter of genes transcribed by RNA polymerase II.

Amanitins↗
PubMed1987

Phorbol ester stimulation of prostanoid synthesis by cultured astrocytes.

The role of protein kinase C in mediating the synthesis and release of various prostanoids (prostaglandins E2, I2, F2 alpha and thromboxane A2) from astroglial cells derived from neonatal rat cerebrum and maintained in primary culture was investigated using phorbol ester. Phorbol myristate acetate stimulated the release of arachidonic acid from prelabelled cells and all 4 prostanoids in a dose-dependent manner (EC50 = 300 nM). This effect was inhibited by the protein kinase inhibitor 1-(-5-isoquinolinylsulfonyl)-2-methylpiperizine (IC50 = 25 microM) and the phospholipase A2 inhibitor, mepacrine (IC50 = 5 microM). In addition, the stimulatory effect of the phorbol ester was not apparent in cells which had been depleted specifically of protein kinase C. In the presence of the calcium ionophore A23187, phorbol ester-stimulated prostanoid release was enhanced. In the absence of extracellular calcium, there was no prostanoid-stimulation by phorbol ester, but the calcium channel blocker verapamil did not mimic this effect. We conclude that stimulation of protein kinase C by phorbol ester elicits prostanoid synthesis and release by a process that involves calcium influx and the activation of phospholipase A2.

Animals↗
PubMed1987

Inositol phospholipids are probably not the source of arachidonic acid for eicosanoid synthesis in astrocytes.

In astrocyte-enriched cultures of the rat cerebral cortex the Ca2+ ionophore A23187 provoked the breakdown of inositol phospholipids, the liberation of arachidonic acid and the release of prostaglandins E2, F2 alpha, I2 and thromboxane A2. However, agonists for receptors also coupled to inositol phospholipid metabolism in these cells failed to produce an increase in the release of both arachidonic acid and eicosanoids. Results suggest that the A23187-stimulated release of arachidonic acid and eicosanoids is caused by a phospholipase A2-mediated attack on lipids other than the inositol phospholipids. Moreover, receptors linked to inositol lipid turnover are not involved in the control of eicosanoid release from astrocytes.

Animals↗
PubMed1987

Differentiation between essential thrombocythemia and polycythemia vera with marked thrombocytosis.

Accurate distinction between essential thrombocythemia and thrombocytotic polycythemia vera requires determination of the red cell mass in the presence of adequate iron stores, but this is not always possible. We therefore compared the clinical and laboratory features at the time of presentation of 50 patients with unequivocal essential thrombocythemia and 27 patients with thrombocytotic polycythemia vera. Univariate analysis failed to identify any single parameter capable of reliably separating the groups. A logistic regression algorithm incorporating hematocrit, white cell count, and spleen size markedly increased the diagnostic accuracy (92%) compared with predictions based on the hematocrit alone (52%). The algorithm's usefulness for patients with intermediate hematocrits was confirmed by analysis of independent samples of essential thrombocythemia and thrombocytotic polycythemia vera patients, and also by analysis of patients with probable essential thrombocythemia in whom the diagnosis could not be confirmed because of inadequate exclusion of polycythemia vera. Furthermore, comparison of survival data suggests that differentiating these disorders is prognostically important. The algorithm is recommended as an alternate method for differentiating essential thrombocythemia from thrombocytotic polycythemia vera whenever the red cell mass is unavailable or iron deficiency cannot be excluded.

Adult↗
PubMed1987

Strains and micromotions of press-fit femoral stem prostheses.

Average femoral geometry was determined from sections of 25 human femurs. A 'stem design program' was used to determine the largest femoral stem that could be introduced into the canal. The stem was fine tuned by observations of fit in Plexiglass models of the 25 femurs. This stem was called the 'Exact-Fit'. Type 1 stem was formed by grinding the anterior and posterior faces flat. Type 2 stem was formed by additionally grinding the medial and lateral faces flat. Four fresh femurs were used for the experiments. Strain gages were located on the proximal medial area and level with the distal lateral tip. Displacement transducers were mounted proximally to measure stem-bone micromotion. Vertical and anterior-posterior forces were applied to the femoral head and normal strain data obtained. The stems were then inserted in sequence and the strains and micromotions were measured. After the uncemented stems had been tested, a smaller size of 'exact-fit' stem was cemented and the tests repeated. The strains with the uncemented stems were closer to normal than with the cemented stems. For example, compressive calcar strains averaged 56% of normal uncemented compared with 30% cemented for the different loadings. The micromotion was higher uncemented, but was still at a low level. The 'exact-fit' stem gave less resultant micromotion than the type 1 and type 2 stems. The high variation of the strain results was attributed to variations in stem-bone contact and fit. The study provided information of direct application to press-fit stems in hip replacement surgery.

Bone Cements↗
PubMed1987

Phorbol ester stimulates proliferation of astrocytes in primary culture.

Near-confluent primary cultures of astrocytes from the neonatal rat cerebral cortex were transferred to low serum (0.1%) growth medium for 24 h before a single addition of phorbol-12-myristate-13-acetate (0.01-100 ng X ml-1), a phorbol ester which mimics diacylglycerol activation of protein kinase C. After 48 h the cultures were pulsed with [methyl-3H]thymidine. Cultures exposed to phorbol ester exhibited dose-dependent increases in thymidine incorporation which were reversed by amiloride.

Amiloride↗