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Biomedical subjects

M Ellis

Publications and source records attributed to M Ellis.

At least 19 recordsLinked to original sources
PubMed1992

Insulin-like growth factor expression in breast cancer epithelium and stroma.

The insulin-like growth factors (IGFs) are mitogens for many cancer cell types. In breast cancer cells, IGF-I and IGF-II have both been shown to stimulate cell proliferation. However, IGF-I mRNA has not been found in human breast cancer cell lines, making it unlikely that IGF-I is commonly expressed as an autocrine growth factor for breast cancer cells. Nevertheless, IGF-I mRNA can be detected in breast cancer tissue samples, and in situ hybridization studies have shown that the message originates from the stromal cells adjacent to normal lobules. IGF-II, on the other hand, has been detected in some breast cancer cell lines. In the estrogen receptor positive cell line T47-D, IGF-II mRNA was induced by estradiol. Furthermore, transfection of an IGF-II expression vector into a previously estrogen-dependent cell line resulted in hormone independent growth. Thus, IGF-II can be expressed as an autocrine growth factor in some breast cancers and its expression may, in part, result in hormone independence. Finally, stromal cells obtained from breast tissues showed that IGF-I was commonly expressed in fibroblasts derived from non-malignant biopsy specimens, while IGF-II mRNA was detected in fibroblasts adjacent to malignant tissue. These studies suggest that IGF-II expression may be important in both autocrine and paracrine regulation of breast cancer cell growth.

Breast↗
PubMed1992

The reproducibility of colour-coded duplex scanning in measuring arterial wall dimensions.

Intimal hyperplasia continues to be a major problem following vascular surgery but experimental evidence suggests that it can be reduced pharmacologically. For clinical studies an accurate, reproducible and non-invasive image of the intima and lumen is required. We have assessed the value of the Acuson 128 Colour Duplex for such studies. Ten patients had their common femoral arteries scanned at a fixed point by two experienced observers on two separate occasions. External vessel diameter, luminal diameter and internal diameter (i.e. the diameter within the internal elastic lamina) were measured in both longitudinal and cross-sectional views. Cross-sectional area and degree of stenosis were all measured and all parameters expressed as limits of agreement. The mean external diameter of the common femoral arteries was 10.5 +/- 1.6 mm. Measurements in the longitudinal view were highly reproducible with limits of agreement ranging from -0.67 - +0.25 mm (internal diameter) to -1.49 - +1.31 mm (luminal diameter). In order to detect a meaningful change in longitudinal external diameter a real difference of 0.86 mm is required representing a change of less than 10%. Cross-sectional diameter measurements were similarly reproducible (-0.73 - +0.47 mm to -1.97 - +1.79 mm). However, cross-sectional area measurements had a wide variation so that the error in degree of stenosis was -25.4 - +30.2%. Thus, duplex ultrasound reproducibly images the layers of the arterial wall. Prospective studies of intimal hyperplasia are feasible but must be based on longitudinal and cross-sectional diameters rather than cross-sectional areas.

Aged↗
PubMed1992

Cyclic AMP response element-binding protein and the catalytic subunit of protein kinase A are present in F9 embryonal carcinoma cells but are unable to activate the somatostatin promoter.

The cyclic AMP (cAMP) response elements (CREs) of the somatostatin and vasoactive intestinal peptide (VIP) promoters contain binding sites for CRE-binding protein (CREB) that are essential for cAMP-regulated transcription. Using F9 embryonal carcinoma cells, we show that the somatostatin and VIP promoters exhibit a differentiation-dependent cAMP response, demonstrating that these promoters are regulated by transcription factors that become active during differentiation. Lack of cAMP responsiveness of the somatostatin promoter in undifferentiated cells is not due to the absence of known positive-acting factors (the catalytic subunit of protein kinase A [cPKA] and CREB) or a general inhibition of protein kinase A activity. Since overexpression of exogenous cPKA and CREB is sufficient to activate the somatostatin promoter in undifferentiated cells, these findings suggest that a negative factor(s) represses endogenous cPKA and CREB. In contrast to their effects on somatostatin, exogenous CREB and cPKA do not activate the VIP promoter. Thus, despite coregulation during differentiation and the ability to bind CREB, the somatostatin and VIP promoters are not coordinately activated by CREB in undifferentiated F9 cells.

Base Sequence↗
PubMed1992

Neonatal meningococcal conjunctivitis associated with meningococcal meningitis.

Two infants are described in whom identical strains of meningococcus were isolated from both the eyes and the cerebrospinal fluid. This suggests that the eye may be a portal of entry in at least some cases of perinatally acquired neonatal meningococcal disease and has important implications for the management of purulent conjunctivitis in the newborn.

Conjunctivitis, Bacterial↗
PubMed1992

A clinical-radiological evaluation of benzimidazoles in the management of Echinococcus granulosus cysts.

Nine patients with complicated hydatid disease managed with surgery and mebendazole/albendazole are presented. Five patients received albendazole (1 treatment course) and 5 patients received mebendazole (3 had 2 treatment courses, 1 had a switch-over from mebendazole to albendazole). The mean durations of treatment and follow-up were respectively 7 +/- 2.5 months and 7 +/- 2.5 months (albendazole); 13 +/- 10 months and 29 +/- 31 months (mebendazole). A superior clinical and radiological response was seen in 1 patient with disseminated intra-abdominal disease on switching therapy from mebendazole to albendazole. Radiological improvement occurred in 3/5 courses of albendazole and in 2/8 courses of mebendazole. Clinical improvement occurred in 3/5 courses of albendazole and 0/8 courses of mebendazole. Radiological deterioration was demonstrated in 0/5 courses of albendazole and 2/8 courses of mebendazole. Although the impression was that albendazole was superior, good responses were also seen with mebendazole. The heterogeneity of the patients, their disease, short follow-up time, lack of more sensitive noninvasive assay techniques urges caution before firm conclusions can be drawn.

Abdomen↗
PubMed1992

Fatal methemoglobinemia caused by inadvertent contamination of a laxative solution with sodium nitrite.

We describe two cases of fatal methemoglobinemia resulting from ingestion of laxative solution inadvertently contaminated with sodium nitrite. Postmortem toxicological examination revealed methemoglobin levels in excess of 75% in both patients--a level that is uniformly fatal. The laxative solution was found to contain sodium nitrite instead of sodium sulphate at a concentration of 15 g/l. The pathophysiology of methemoglobinemia and a review of other reported cases of toxic methemoglobinemia are presented. Marked cyanosis in the face of intact cardiorespiratory function should alert the physician to the possibility of toxic methemoglobinemia.

Aged↗
PubMed1991

Limitations of ultrasonography in surveillance of small abdominal aortic aneurysms.

The repeatability, observer bias and instrument bias of aortic diameter measurement by ultrasonography, were investigated in ten patients with small (3-6 cm by computed tomography) infrarenal abdominal aortic aneurysm. The repeatability of maximum aortic diameter measurement by ultrasonography was much better for anterior-posterior than transverse diameter, with coefficients of repeatability 3.0-7.5 mm and 10-15 mm respectively. The repeatability of suprarenal aortic diameter measurement was poor. Surprisingly, maximum diameter using ultrasonography was larger than that using computed tomography, the difference being least for anterior-posterior measurements. At best a single, experienced observer, using the same instrument may provide aortic diameters using ultrasonography accurate to within 5 mm, but more commonly such aortic diameter is only accurate to within 8 mm.

Aorta, Abdominal↗
PubMed1991

Activities of enzymes of the pancreas, and the lumen and mucosa of the small intestine in growing broiler cockerels fed on tannin-containing diets.

Diets containing vegetable tannins, predominantly hydrolysable gallotannins, at levels of 13.5, 25 and 50 g/kg were fed to growing broiler cockerels to examine their effect on enzymes in the pancreas, the intestinal lumen and the intestinal mucosa. Pancreas weight per unit live weight showed a significant (P less than 0.05) increase with increasing level of dietary tannin while that of the liver remained unaffected. Trypsin (EC 3.4.21.4) and alpha-amylase (EC 3.2.1.1) activities in the pancreas of birds fed at the highest level of tannins were more than double those from birds fed on a tannin-free control diet. In the intestinal lumen inhibition of trypsin activity increased with increasing level of dietary tannin; alpha-amylase activity was inhibited at intermediate tannin levels but was restored at the highest level. Dipeptidase (EC 3.4.13.11) and sucrose alpha-glucosidase (disaccharidase) (EC 3.2.1.48) in the intestinal mucosa were both inhibited by tannins. Growth of the birds and digestibility of nitrogen were adversely affected by the tannin-containing diets.

Animal Feed↗
PubMed1991

L-type cardiac calcium channels in doxorubicin cardiomyopathy in rats morphological, biochemical, and functional correlations.

Doxorubicin (DXR) is an effective antitumor agent in a wide spectrum of neoplasms. Chronic treatment is associated with cardiomyopathy and characteristic myocardial ultrastructural changes, which include swelling of the t tubules. Accordingly, we investigated excitation-contraction coupling in cardiomyopathic rat heart resulting from chronic DXR treatment. Using the whole-cell patch clamp technique, we studied the L-type calcium channel in single cells enzymatically isolated from normal (CTRL) and DXR rat hearts. Despite similar cell dimensions, the total membrane capacitance was significantly smaller in the DXR cells (138 +/- 9 pF) than in the CTRL cells (169 +/- 11 pF) (mean +/- SEM, n = 9, P less than 0.05). The mean current and the current density-voltage relationships of the CTRL and the DXR cells were significantly different (n = 9, P less than 0.001) with the maximal peak L-type calcium current (ICa) density increased from 6.4 +/- 0.9 in CTRL cells to 10.5 +/- 2.4 microA/cm2 in the DXR cells (P less than 0.05). There was no shift either in the current-voltage relationship or the steady-state inactivation curve in the two cell groups. However, the fast time constant of inactivation was increased at a membrane voltage of -10 to 10 mV. Calcium channel antagonist equilibrium binding assays using [3H]-PN200-110 revealed no difference in the maximal receptor binding capacity (CTRL, 194 +/- 27 and DXR 211 +/- 24 fmol/mg protein; P greater than 0.05, n = 6) and in receptor affinity (CTRL, 0.15 +/- 0.05 and DXR 0.13 +/- 0.03 nM; P less than 0.05). These data suggest that a decrease in effective capacitance might be associated with t-tubular damage. Despite this decrease, ICa was increased in the DXR cells. Such an increase may result from an alteration in the properties of the calcium channels and/or recruitment of "hibernating" channels in the remaining surface and t-tubular membranes.

Animals↗
PubMed1990

Synergistic cytotoxicity using 2'-deoxy-5-azacytidine and cisplatin or 4-hydroperoxycyclophosphamide with human tumor cells.

The combined use of 2'-deoxy-5-azacytidine with cisplatin or 4-hydroperoxycyclophosphamide in vitro frequently resulted in synergistic cytotoxicity against a panel of six human cell lines. This enhanced cell killing occurred at drug concentrations that are clinically achievable. Synergy was also seen if the sequence of drug administration was altered, implying that a temporal overlap between the drugs was necessary, but that the actual biochemical lesions induced by each agent were probably unique, and interacted in an as yet undefined manner. Of further interest was the observation that at least one of the synergistic pairs was active against five of the six cell lines tested. 2'-Deoxy-5-azacytidine incorporation as assessed by the level of gross genomic DNA methylation did not appear to correlate with the synergistic cytotoxicity observed. Thus, we could not discern a clear relationship between the degree of DNA hypomethylation and the observed synergies, although DNA hypomethylation frequently occurred when synergy was demonstrated. The practical usefulness of these drug combinations has not yet been tested and awaits appropriate clinical trials both to assess the tumoricidal effects and possible increased toxicity.

Antineoplastic Agents↗
PubMed1990

Locomotor disability in very elderly people: value of a programme for screening and provision of aids for daily living.

OBJECTIVE: To assess the prevalence of potentially reversible locomotor disabilities in elderly subjects and the cost effectiveness of providing aids for daily living. DESIGN: Population based randomised controlled trial of subjects aged greater than or equal to 85 living independently in an inner London borough. SETTING: 21 Electoral wards of the London Borough of Hackney. SUBJECTS: 1255 Subjects aged greater than or equal to 85 living in their own home whose names were obtained from general practitioner lists and cross checked against the electoral register, 511 of whom were subsequently found to be ineligible. Of the 744 remaining, those with disability on screening were randomised and allocated to an intervention group (36) or a control group (43), in which intervention was postponed until four weeks, after the follow up assessment. Subjects with aids supplied previously were excluded from the intervention phase. INTERVENTIONS: Provision of raised toilet seat, teapot tipper, tap turner, shoe horn and elastic laces, and double handled saucepan. MAIN OUTCOME MEASURES: Degree of difficulty (grades 1-4) with specific tasks (getting on and off a toilet, pouring from a teapot into a cup, turning taps on and off, carrying a saucepan of standard weight, and putting on shoes) and time taken to perform them. RESULTS: 545 (73%) Of the 744 eligible subjects assessed; 428 had no disability and 118 had difficulty with at least one task. Some had had their disability recognised before the study and already had aids, representing half of those with difficulty getting on and off the toilet but 24% for putting on shoes and 13% for pouring from a teapot and turning on a tap. The mean number of difficulties was similar between the groups (intervention group 1.7, control group 1.6). Time taken to complete the tasks corresponded with the observed grade of difficulty. All aids were associated with reduced difficulty according to observer assessment (% improvement intervention group v control group: raised toilet seat, 71 v 13 teapot tipper 100 v 33; tap turner 100 v 0; saucepan 88 v 0; shoe horn 50 v 13) and time taken to complete the tasks. A cost benefit analysis of this screening-intervention programme suggested a total cost of 32 pounds per individual benefit. CONCLUSIONS: Appreciable degrees of unrecognised locomotor disability are detected on screening of very elderly people living independently. Providing aids offers a feasible and cost effective means of improving function in such people.

Activities of Daily Living↗
PubMed1990

Rubella.

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Child, Preschool↗
PubMed1989

Biochemical analysis of the role of transmethylation in the methionine dependence of tumor cells.

The effects on methionine metabolism of the substitution of homocysteine for methionine in vitro were investigated in normal and tumor cell lines differing in their ability to utilize homocysteine for growth. The major finding of this study was that methionine-independent (Met-Indep) cell lines had much lower basal transmethylation rates than methionine-dependent (Met-Dep) cell lines. This was particularly evident in the parent SP1 cell line and its Met-Indep revertant, SP1-R. SP1-R compensated for a lack of methionine by reducing both its transmethylation and growth rates. An analysis of other potential differences in methionine metabolism between Met-Dep and Met-Indep cell lines failed to demonstrate any consistent abnormalities in all but the absolutely Met-Dep MDAY-D2 cell line. Thus, protein, S-adenosylmethionine, and polyamine synthesis were the same in Met-Dep and Met-Indep cell lines. These results indicate that the major regulatory step in determining the Met-Dep phenotype is an inherent increase in the rate of transmethylation reactions. Cell lines with high basal transmethylation rates cannot compensate for a relative deficiency of methionine and either cease growing (MDAY-D2) or generate revertants (SP1-R) for which the basal rate of transmethylation is considerably reduced.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1989

Cyclic AMP does not alter taurine accumulation by rat renal brush border membrane vesicles.

Secondary hyperparathyroidism has been attributed to be responsible for the generalized aminoaciduria and phosphaturia of vitamin D deficiency. Since PTH acts in the kidney to generate cAMP, we explored the possibility that its synthetic analog, dbcAMP, would alter the renal transport of taurine (an amino acid lost in the urine in vitamin D deficiency) and Pi. Exposure of renal BBMV prepared from normal and vitamin D-calcium-deficient rats to dbcAMP at concentrations ranging between 10(-4) and 10(-7) M did not alter taurine uptake by these vesicles. Higher dbcAMP concentrations blunted uptake, but these concentrations reduced intravesicular volume, thus representing an artifact of osmolarity. Preincubation of BBMV with dbcAMP for times between 0 and 60 min at 0 or 25 degrees C also did not alter taurine accumulation. Hypotonic lysis of BBMV, allowing entry of the cyclic nucleotide, followed by isotonic resealing did not influence taurine uptake. The addition of potassium fluoride (to inhibit phosphodiesterase activity) and ATP (as an energy source) did not alter taurine accumulation at 60 sec. The uptake of Pi, which is influenced by PTH, was decreased by 25% following exposure to dbcAMP on the internal surface of the vesicle. These data indicate that the taurinuria observed in vitamin D deficiency is unlikely to be related to a PTH-induced increase in intracellular cAMP, unlike the changes in Pi transport, which is sensitive to cyclic nucleotides.

Adenosine Triphosphate↗
PubMed1989

Therapy for symptoms in the carcinoid syndrome.

The clinical course and results of drug treatment for manifestations of the carcinoid syndrome are reviewed in 63 patients. The five-year actuarial survival in this group of patients was 48 per cent. The only markers of a poor prognosis that could be identified at diagnosis were marked weight loss and a high (over 1000 mumol/day) 5-hydroxyindole acetic acid excretion. The relative effectiveness of well-established drugs that either block 5-hydroxytryptamine synthesis or block 5-hydroxytryptamine receptors is reported, with respect to the different manifestations of the syndrome, and compared with a small group of patients treated with long-acting somatostatin analogue. In over one-third of patients, primary tumours were not detected on initial investigation, and in none of these did symptoms referrable to the primary site become apparent later.

Adult↗
PubMed1986

Advances in the management of testicular cancer.

Dramatic advances have been made over the last decade in the management of testicular cancer. There are three identifiable reasons for this. The first is the widespread availability of tumour markers to assess the state of disease and its response to therapy. The second is CT scanning, which has revolutionized our ability to locate with fine anatomical detail the location of metastases. The third is the development of effective, intensive chemotherapy together with the understanding of its side-effects and optimum usage. Problems still remain in patients who fail to respond completely to existing therapy. In addition, the profound side-effects of chemotherapy mean that much effort is being invested in the development of less toxic but equally effective forms of treatment.

Antineoplastic Combined Chemotherapy Protocols↗