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Biomedical subjects

D Owen

Publications and source records attributed to D Owen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus megestrol acetate/placebo in extensive-stage small-cell lung cancer: a North Central Cancer Treatment Group study.

PURPOSE: Megestrol acetate has been reported to improve appetite and quality of life and to decrease nausea and vomiting in patients with cancer anorexia/cachexia. The present trial was formulated to evaluate the impact of megestrol acetate on quality of life, toxicity, response, and survival in individuals with extensive-stage small-cell lung cancer who received concomitant chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive megestrol acetate 800 mg/d orally or placebo. In addition, all patients were scheduled to receive a maximum of four cycles of cisplatin and etoposide chemotherapy. Quality of life was self-assessed at entry onto study, with every cycle of chemotherapy, and 4 months thereafter with a linear visual analog scale. Toxicity was evaluated by patient questionnaire and investigator reports. RESULTS: A total of 243 eligible patients were randomized. Those who received megestrol acetate had increased nonfluid weight gain (P = .004) and significantly less nausea (P = .0002) and vomiting (P = .02). Significant thromboembolic phenomena occurred more often in patients who received megestrol acetate versus placebo (9% v 2%, P = .01). Patients who received megestrol acetate had more edema (30% v 20%, P = .002), an inferior response rate to chemotherapy (68% v 80%, P = .03), and a trend for inferior survival duration (median, 8.2 v 10.0 months, P = .49). These findings may have been influenced by a poorer quality of life of the megestrol acetate group at study initiation. There were no significant changes in quality of life scores over time between either of the study arms. CONCLUSION: Megestrol acetate cannot be routinely recommended for all patients with small-cell lung cancer at the time of chemotherapy initiation. Rather, its therapeutic ratio may be more favorable for patients with problematic cancer anorexia/cachexia.

Anorexia↗
PubMed1995

Ras binding to a C-terminal region of GAP.

Using fluorescence spectroscopy we have identified a binding region for Ras on the GTPase activating protein (GAP) lying within residues 715-753. A synthetic peptide Y922, corresponding to residues 716-753 of GAP binds to wild type Ras showing 3.3-fold higher affinity for the GTP- over the GDP-bound forms of Ras. Binding is stabilised by Mg2+, although Y922 does not stimulate the GTPase activity of Ras. Peptide binding to the Y32A and Y40F Ras mutants showed equal affinity for both GDP- and GTP-bound forms, with binding to Y32A.GDP abolished in the absence of Mg2+. These results suggest that Y922 mimics the in vivo interactions shown by the intact p120GAP protein and provide the first direct demonstration of Ras interaction with GAP in the region 715-753.

Amino Acid Sequence↗
PubMed1995

The high levels of p53 present in adenovirus early region 1-transformed human cells do not cause up-regulation of MDM2 expression.

The cellular protein MDM2 can bind to the tumor suppressor gene product p53 and abrogate its transcriptional activity. In addition, p53 can regulate expression of the mdm2 gene. We and others have previously shown that p53 is present at high levels in adenovirus-transformed cells which express the larger E1B protein. In view of these observations the expression of MDM2 in a panel of adenovirus transformed human cell lines has been examined. Two major species (98K and 80K) were detected, together with a number of minor species of higher and lower molecular weight. While there was little variation in levels of 98K protein between cell lines, appreciable differences in the expression of the 80K component were apparent. There was no correlation between MDM2 and p53 expression in any of the adenovirus transformants, nor with the viral proteins expressed. The pattern and level of MDM2 detected was similar to that seen in human tumor cell lines and in human fetal tissue. Northern blot analysis suggested that MDM2 expression was regulated at the transcriptional level. Stable interactions were observed between p53 and MDM2 in the adenovirus-transformed cell lines and in Ad5 E1 HEK 293 cells a ternary complex of p53, MDM2, and the Ad5 E1B 58K protein was demonstrated. In view of the lack of correlation between the level of p53 and MDM2 in adenovirus E1-transformed cells, the capacity of p53 to cause transcriptional activation was assessed using transfected CAT constructs linked to p53 responsive elements. p53 transcriptional activity was similar in all of the cell lines examined and did not correlate with protein expression. It is concluded, on the basis of all of these data, that the high concentrations of p53 found in adenovirus transformants are not transcriptionally active and have no influence on MDM2 expression. However, when expression of p53 was increased following infection with mutant adenoviruses, which do not express the larger E1B proteins, there was an appreciable increase in p53 transcriptional activity and in the levels of all of the MDM2 components.

Adenovirus E1B Proteins↗
PubMed1995

A novel protein expressed in mammalian cells undergoing apoptosis.

Human and rodent cells undergoing apoptosis were observed to express high levels of a novel 45,000 M(r) protein. The protein, which we have termed apoptosis specific protein (ASP), was found in Burkitt lymphoma (BL) cells and in adenovirus-transformed human and rat embryo cells induced into apoptosis by a variety of stimuli, including serum deprivation, exposure to the Ca2+ ionophore, ionomycin, treatment with inhibitors of macromolecular synthesis (cycloheximide and actinomycin D), and cold shock. In BL cells treated with apoptotic stimuli, expression of the oncoprotein Bcl-2 was found to both protect from apoptosis and prevent expression of ASP. ASP was not detected either in viable cells or in cells dying passively by necrosis. Laser scanning confocal microscopy showed high levels of ASP in the cytoplasm of cells displaying the chromatin condensation and fragmentation patterns typical of apoptosis. Retention of ASP was observed even when DNA was no longer detectable, and two-color immunofluorescence staining indicated that the protein primarily colocalized with, but was clearly distinct from, non-muscle actin. These findings, together with the observation that biochemical extraction of ASP was only possible under conditions which caused solubilization of the cytoskeleton, leads us to conclude that ASP forms part of, or at least strongly associates with, a modified cytoskeleton unique to cells undergoing apoptosis. While elucidation of its function will require further work, ASP constitutes a powerful marker for the diagnosis and quantitation of apoptosis in vivo and in vitro.

Animals↗
PubMed1995

Application of pulsed field gel electrophoresis to the 1993 epidemic of whooping cough in the UK.

The purpose of this study was to DNA fingerprint the majority (64%) of isolates received at the Pertussis Reference Laboratory during the 1993 whooping cough epidemic by pulsed field gel electrophoresis of Xba I-generated restriction digests. Two DNA restriction patterns, types 1 and 3, predominated (40% and 23%, respectively, of 180 isolates) but type 2, identified in a previous study was notably absent. Twenty-one new DNA types occurred (24% of isolates), some being atypical as bands 155-230 kb were no longer conserved, but there was no statistically significant difference in their incidence in the upswing (June-September) compared to the downswing (October-December) phase of the epidemic. There was a relatively high proportion of new types, compared to type 1, at the peak (September). About 50% of isolates received were from the North Western Region, where 44% of isolates were DNA type 1. Whereas only 1 out of 10 isolates from Scotland were of this type, suggesting some geographic variation. Statistically significant findings included a higher proportion of isolates from female patients (P < 0.01), most marked in the 12-24 months age group (P < 0.05); a higher proportion of infants under 12 months requiring hospital admission compared to older children (P < 0.05); and a greater number of isolates from unvaccinated children (P < 0.01). Analysis of serotype according to four age groups (under 3 months, 3-12 months, 12-24 months and above 2 years) showed statistically significant differences (P < 0.05) with a noticeably lower proportion (38%) of serotype 1,3 in 3-12 months age group and higher prevalence (74%) of serotype 1,3 in the 12-24 months age group. There was no correlation between DNA type and serotype.

Age Factors↗
PubMed1995

The spatial and socio-economic patterns of minority ethnic groups in Great Britain.

"This paper considers the manner in which people from minority ethnic groups relate to the spatial and socio-economic organisation of Great Britain. It presents a classification of local authority districts based on 1981 and 1991 Census data and explores the distribution of nine minority ethnic groups across the eight types of district identified. The socio-economic characteristics of minority ethnic groups in each cluster are then examined in order to determine the types of locality in which minority ethnic groups fare relatively well or badly."

Culture↗
PubMed1995

Mechanisms of alphafetoprotein transfer in the perfused human placental cotyledon from uncomplicated pregnancy.

We investigated the mechanisms of alphafetoprotein (AFP) transfer across the human placenta by correlating measurements of AFP transfer with cytochemical localization of AFP. Placental cotyledons were dually perfused in vitro with either the fetal or maternal perfusate containing umbilical cord plasma as a source of AFP. Steady state AFP clearance, corrected for release of endogenous AFP, was 0.973 +/- 0.292 microliter/min per gram in the fetal to maternal direction (n = 10), significantly higher (P < 0.02) than that in the maternal to fetal direction (n = 5; 0.022 +/- 0.013 microliter/min per gram). Clearance of a similarly sized protein, horseradish peroxidase was also asymmetric but clearance of the small tracer creatinine was not. Using a monoclonal antibody, we localized AFP to fibrinoid deposits in regions of villi with discontinuities of the syncytiotrophoblast, to cytotrophoblast cells in these deposits, to syncytiotrophoblast on some villi, and to trophoblast cells in the decidua. We conclude that AFP transfer in the placenta is asymmetric and that there are two available pathways for AFP transfer: (a) from the fetal circulation into the villous core and across fibrinoid deposits at discontinuities in the villous syncytiotrophoblast to enter the maternal circulation; and (b) AFP present in the decidua could enter vessels that traverse the basal plate.

Biological Transport↗
PubMed1994

Diurnal visual changes in radial keratotomy: implications for visual standards. Refractive Surgery Study Group.

BACKGROUND: Diurnal variations in vision have been reported in radial keratotomy (RK) patients. Applicants to certain professions may meet an uncorrected vision standard at the time of testing but fail to meet that standard at another time. METHODS: Ten firefighter applicants who had undergone RK and nine normal subjects attended for two morning visits, and two afternoon visits. At each visit subjective refraction, uncorrected visual acuity, best-corrected visual acuity, automated refraction, and keratometry were measured for each eye. Monocular contrast sensitivity was measured using the Pelli-Robson chart with and without a glare source (brightness acuity tester, BAT) and for both natural and dilated pupils. RESULTS: The RK group showed a significant myopic shift from morning to afternoon (mean = -0.41 +/- 0.33 D; t = 3.92, p = 0.004), which was well correlated (r = -0.86) with significant steepening of the corneal curvature (mean = +0.41 +/- 0.36 D; t = -3.65, p = 0.005). The controls showed no change in either refractive error (mean change = +0.06 +/- 0.42 D) or corneal curvature (mean change = +0.05 +/- 0.08 D). No significant difference in corrected visual acuity or contrast sensitivity was found between the RK and control groups for natural pupils. For dilated pupils, the RK patients showed significantly poorer log contrast sensitivity both with and without glare (RK mean = 1.49 +/- 0.11; control mean = 1.67 +/- 0.11; t = 3.21, p = 0.005). All RK subjects met the firefighter visual acuity standard on the initial visit, three subjects did not meet the standard at an afternoon examination. DISCUSSION: We propose that, if RK applicants are to be considered for employment, existing visual standards be amended to include visual acuity testing in both the early morning and late afternoon. Clinicians and agencies should also be aware that contrast sensitivity may be reduced at low light levels.

Adult↗
PubMed1994

Blockade by dendrotoxin homologues of voltage-dependent K+ currents in cultured sensory neurones from neonatal rats.

1. Homologues of dendrotoxin (Dtx) were isolated from the crude venom of Green and Black Mamba snakes and examined for K+ channel blocking activity in neonatal rat dorsal root ganglion cells (DRGs) by whole-cell patch clamp recording. 2. Outward potassium current activated by depolarization was composed of two major components: a slowly inactivating current (SIC, tau decay approximately 50 ms, 200 ms and 2s), and a non-inactivating current (NIC, tau decay > 2 min). Tail current analysis revealed two time constants of deactivation of total outward current, 3-12 ms and 50-150 ms (at -80 mV) which corresponded to SIC and NIC, respectively. 3. All the homologues (alpha-, beta-, gamma- and delta-Dtx and toxins I and K) blocked outward current activated by depolarization in a dose-dependent manner. The most potent in blocking total outward current was delta-Dtx (EC50 of 0.5 +/- 0.2 nM), although there were no statistically significant differences in potency between any of the homologues. 4. Qualitative differences in the nature of the block were noted between homologues. In particular, the block by delta-Dtx was time-dependent, whereas that by alpha-Dtx was not. 5. alpha-Dtx was a much better blocker of SIC (EC50 = 1.0 +/- 0.4 nM) than was delta-Dtx (EC50 = 17.6 +/- 5.8 nM). Furthermore, delta-Dtx was selective for NIC (EC50 +/- 0.24 +/- 0.03 nM) over SIC and reduced the slow component of tail currents (NIC), preferentially. On the other hand, a-Dtx did not significantly distinguish between SIC and NIC although tail current analysis showed that a-Dtxpreferentially reduced the fast component of tail currents (SIC).6. The results confirm, using direct electrophysiological methods, that homologues of dendrotoxins from Mamba snake venom block K+ channels in rat sensory neurones. Furthermore, a-Dtx and 6-Dtx distinguish between sub-types of K+ channels in these cells and may thus be useful pharmacological tools in other neuronal K+ channel studies.

Animals↗
PubMed1994

Spatial variations in ethnic minority group populations in Great Britain.

This article is concerned with contrasts in the geographical distribution of people from the white and ethnic minority groups within Great Britain. It begins by describing regional variations in ethnic composition and maps the distribution of ethnic minority groups at the local authority district scale. The article then demonstrates that most people from the white ethnic group live in wards with very small populations from ethnic minority groups, while people from ethnic minority groups tend to be found where the share of minorities in the resident population is relatively high. The focus then switches to the neighbourhood (enumeration district) scale, at which a very marked degree of spatial segregation in the distribution of ethnic groups is revealed. The local authority districts in which the degree of segregation of people from ethnic minority groups relative to the rest of the population is greatest are listed.

Africa↗
PubMed1993

Not exclusive.

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Gene Expression Regulation↗
PubMed1993

Blunt traumatic liver injury associated with clostridial infection of early onset.

Hepatic clostridial infections associated with blunt abdominal trauma are rare. Generally they occur from 2 weeks to 3 months after injury and are thought to result from the growth of normal enteric organisms, which are carried to the liver by the portal venous system and infect devitalized tissue. The authors describe two patients in whom the hepatic infection became established in less than 24 hours after injury and was due to Clostridium spp. The patients were successfully treated by hepatic resection and combination antimicrobial therapy. Hyperbaric oxygen was used as an adjunct in one case.

Abdominal Injuries↗
PubMed1992

Maturation of the filaria Litomosoides sigmodontis in BALB/c mice; comparative susceptibility of nine other inbred strains.

When inoculated subcutaneously, the infective larvae of L. sigmodontis undergo complete development and produce a patent microfilaraemia in mice of the BALB background (BALB/c, BALB/K and BALB/B, with respectively the H-2d, H-2k et H-2b haplotypes). The most susceptible strain is BALB/c with all mice harbouring adult filariae and 47% of mice presenting with a patent microfilaraemia. Mice with the B10 background (B10, B10Br and B10D2, with respectively the H-2b, H-2k et H-2d haplotypes) are almost completely resistant to infection. Adult filariae were recovered from all mice of the CBA/Ca, CBA/HN, C3H/HeN, DBA/2N strains. However, the site and structural development of the parasite varied in each strain. Absence of microfilaraemia is associated with absent or abnormal spicules, reduced number of female filariae and small size of female filariae. These results show that the Major Histocompatibility Complex only modulates the developmental pattern of filariae within the limits imposed by background genes. Male CBA/HN and C3H/HeN were more susceptible to infection than female mice. Inverse phenomenon was observed with strains BALB/c; and, no host sex effect was seen in DBA/D2N.

Animals↗