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Biomedical subjects

L Russell

Publications and source records attributed to L Russell.

At least 37 records · Page 2Linked to original sources

Crisis management to controlled recovery: the emergency planning response to the bombing of Manchester City Centre.

Fuelled by terrorist attacks on urban areas, emergency planning responses to manmade disasters is a growing area of critical debate within the field of urban management. The response of a major British city--Manchester--to the 1996 bombing of its commercial core, is examined in this paper. It focuses on the transformation of the emergency planning response from dealing with the immediate crisis during the first week, to a stage of controlled recovery that still continues. The response to the devastation caused by the bomb was co-ordinated by the city council, which developed a range of short- and long-term initiatives, but the re-opening of the city centre could not have happened so quickly had the council not worked in collaboration with other key organisations and agencies. Working partnerships were crucial to the immediate response and subsequent recovery, with such capacity for organisational learning built upon existing co-operative arrangements within the city, which had developed over the previous decade.

Crisis Intervention↗

Effect of supplemental sodium chloride and hydrochloric acid added to initial starter diets containing spray-dried blood plasma and lactose on resulting performance and nitrogen digestibility of 3-week-old weaned pigs.

Four experiments evaluated the efficacy of Na or Cl or their combination added to weanling pig diets that contained plasma protein and lactose on pig performance and N digestibility. The four experiments used a total of 563 crossbred pigs weaned at 22+/-1 d of age averaging 6.4 kg body weight. The basal diet in each experiment contained 5.8% plasma protein and 20% lactose and analyzed .20% Na and .23% Cl. In Exp. 1, NaCl was added to treatment diets at 0, .20, .40, or .60%. The trial was conducted for a 21 d period in a randomized complete block (RCB) design in seven replicates. Improved growth rates (P < .01) and gain:feed ratios (P < .01) occurred up to a dietary salt level of .40%. In Exp. 2, we evaluated the interaction of Na and Cl on pig performance. The experiment was a 2 x 2 factorial arrangement in a RCB design conducted in seven replicates. Total dietary Na was .20 or .36%, and Cl was included at .25 or .45%. Although there was a numerical increase in pig gains with added Na, the response was not significant (P > .15), but both gains (P < .01) and gain:feed ratios (P < .01) increased at the higher dietary Cl level. In Exp. 3, we evaluated the effect of five dietary levels of Cl added at .06% increments to a basal diet that analyzed .34% Na and .20% Cl on postweaning pig performance. The experiment was a RCB design conducted in eight replicates. A growth response (P < .01) to the .38% Cl level occurred during the initial 14-d postweaning period and to the .32% Cl level from 14 to 21 d. Gain:feed ratio increased each week with added Cl, but it was significant only for the period from d 0 to 7 d (P < .01). A N digestibility trial, using the diets of Exp. 3, constituted Exp. 4, and groups of three pigs per stainless steel metabolism crate were pair-fed to pigs fed the basal diet. The experiment was a RCB design conducted in three replicates over a 3-wk period. The results demonstrated a weekly decrease in fecal N (P < .01), no effect on urinary N (P < .15), improved N retention (P < .01), and an improved apparent N digestibility (P < .01) to the .38% dietary Cl concentration during the initial 2 wk postweaning. These experiments suggest that although plasma protein contributed Na and Cl to the initial diets of weaned pigs, additional Na and Cl, but particularly Cl, improved pig growth, N retention, and N digestibility. The results suggest a dietary minimum of .38% total Cl level during the initial 2 wk postweaning.

Animal Feed↗

Severe hemolytic reaction due to anti-JK3.

A 35-year-old gravida 3, para 3 Filipino woman with a negative antibody screen, no prior history of transfusion, and no hemolytic disease of the newborn in her children suffered a massive postpartum hemorrhage requiring transfusion. A severe hemolytic transfusion reaction occurred 5 days after delivery. Subsequently, a panagglutinin on a routine antibody identification panel was identified as anti-Jk3. The patient's red blood cell phenotype was Jk(a-b-) and all of her children were Jk(a-b+), yet the antibody that formed reacted with equal strength against all Jk(a)- or Jk(b)-positive cells. The rare Jk(a-b-) phenotype is more common in Polynesians. Anti-Jk3, like other Kidd system antibodies, is difficult to detect because in vivo production may be absent between provocative episodes and because these antibodies often show weak in vitro reactions. The increasing numbers of Pacific Islanders in the United States could result in more frequent encounters with this rare phenotype. Increased awareness of ethnic variability in blood phenotypes and of the capricious nature of Kidd antibodies can help pathologists and technologists deal more effectively with these cases.

Adult↗

Increased cell surface exposure of fucose residues is a late event in apoptosis.

Apoptosis is a well defined physiological process characterised by many specific features including DNA fragmentation and protease activation. Cell membrane-associated changes such as the altered exposure of phosphatidylserine and glycosylation patterns have also been described. We investigate here the change in exposure of surface alpha-L-fucose residues during thymocyte and P815 cell apoptosis. We show that apoptosis in these cells induced by dexamethasone, gliotoxin or thapsigargin was associated with an increase in the exposure of terminal fucose residues. Furthermore, this increase in fucose exposure occurred late in the apoptotic process. The observation of increased fucose exposure in two different cell types by three different apoptosis-inducing agents suggests it may be part of the normal apoptotic process.

Animals↗

Development and validation of the Burton Score: a tool for nutritional assessment.

This paper describes the development and validation of the Burton Score, a nutritional assessment tool based on the Waterlow score, with the rationale that since nurses already collect data for one score, it would only lead to unnecessary duplication of effort if a totally different scoring scheme were to be used for nutritional assessment. Initial cut offs were determined by a pilot study of 26 patients on an elderly care ward and validated by comparing the nutritional status of 263 patients estimated by the Burton score with a dietitian's assessment of nutrition. The validation study showed that although there was significant correlation between the Burton and Waterlow scores the Burton score correlated more closely with the dietitian's assessments. The King's Fund report of 1992 stated that all patients should have assessment of nutritional status on admission to hospital: we believe the Burton score could provide a simple tool to achieve this goal.

Energy Intake↗

Expression and processing of G0/G1 switch gene 24 (G0S24/TIS11/TTP/NUP475) RNA in cultured human blood mononuclear cells.

The human G0/G1 switch (G0S) gene, G0S24, and its rodent immediate-early homolog (TIS11, TTP, NUP475) are part of a mammalian gene family whose members encode CCCH zinc finger domains and domains similar to part of the large subunit of RNA polymerase II and to the Mei2 regulator of G1 arrest in fission yeast. We compared the RNA expression of G0S24 with that of other G0S genes in cultured blood mononuclear cells and examined the levels of various RNA processing intermediates. Freshly isolated cells contained high levels of several G0S RNAs, which declined by 24 h, suggesting transient spontaneous stimulation during cell purification (Heximer et al., 1996). However, in cells preincubated for 24 h, G0S24 RNA levels remained much higher than those of other G0S genes (107+/-42 x 10(6) molecules/microg of RNA); stimulation with lectin (Con-A) further increased G0S24 RNA, much of which remained nuclear. Like those of FOS/G0S7, EGR1/G0S30 and of the gene encoding the regulator of G protein signalling 1 (RGS1), G0S24 RNA levels increased more in response to a protein kinase C activator than to a calcium ionophore, whereas the opposite held for FOSB/G0S3 and RGS2/G0S8. With appropriate PCR primer pairs, we showed a G0S24 RNA processing intermediate, which crossed the exon-1/intron boundary, and nonpolyadenylated nuclear RNA extending into the 3' flank, where there is a second CpG island. The concentration of the latter intermediate (1.2+/-0.2 x 10(6) molecules/microg of RNA), which increased transiently on cell stimulation, did not account for all G0S24 nuclear RNA. The levels of G0S24 RNA and both intermediates were increased by the protein synthesis inhibitor cycloheximide, consistent with regulation by a labile repressor.

Base Sequence↗

The normal copy of the G0S19-3-associated, CpG island-containing, upstream sequence is downstream of G0S19-2/MIP1alpha in association with a TRE17 oncogene.

The G0S19-1/MIP1alpha and G0S19-2/MIP1alpha genes locate to human chromosomes 17q and encode similar copies of the beta-chemokine G0S19/MIP1alpha. The G0S19-3 gene, present in 1 in 4 humans, is a 5' truncated version of G0S19-2; a CpG island-containing upstream sequence (CpG-US), rich in potential transcriptional activation motifs, replaces much of the first intron and the first exon. Sequences hybridizing with the CpG-US sequence, normally exist in all human genomes. Thus, it appears that there has been recombination between a duplicated G0S19 gene and a duplicated CpG-US-like sequence. We have isolated sequences hybridizing with the CpG-US sequence from a human genomic library in bacteriophage lambda. Restriction mapping and sequencing shows a CpG-US-like sequence approximately 8 kb downstream of G0S19-2 (hence, named CpG-DS sequence). The sequence is contiguous with a TRE17 oncogene-associated sequence (GenBank locus HSTRE175). Members of the TRE17 family are known to locate to chromosome 17q (Onno et al., 1993b), and have sequence characteristics suggestive of positive Darwinian selection. Linkage with a TRE17 oncogene may have arisen by recombination and imply no functional relationship. However, it is possible that the CpG-DS may normally regulate TRE17 expression. PCR and sequencing studies indicate the close proximity of other chemokine-related sequences in the 17q11.2 region.

Amino Acid Sequence↗

Longitudinal lipid profiles on CAPD: their relationship to weight gain, comorbidity, and dialysis factors.

The dyslipidemia of chronic renal failure may worsen after the commencement of continuous ambulatory peritoneal dialysis (CAPD). The purpose of this study was to relate baseline and longitudinal changes in the lipid profile to anthropometrics (weight, mid-arm circumference), aspects of treatment (albumin, total protein losses, peritoneal solute transport [dialysate:plasma ratio of creatinine], dialysate caloric load), total calorie intake (cal/kg), preexisting cardiovascular comorbidity, and survival. Lipid profiles (triglycerides [TG], total cholesterol [TC], and HDL) were measured, along with the above factors, every 6 mo in an unselected prospective cohort of 124 patients who were not treated with lipid-lowering drugs, commencing CAPD between 1990 and 1993, until 1995. On univariate analysis, age, plasma albumin, cardiovascular disease, baseline TG, and TC:HDL ratio predicted survival. Simultaneous multiple Cox regression including all of the significant predictors demonstrated that either high TG or TC: HDL still predicted death, both in patients with and without clinically overt cardiovascular disease. Between 6 and 36 mo of treatment, TC, TG, and TC:HDL were elevated when compared with the baseline, more so in patients with preexisting cardiovascular disease (P < 0.05). Throughout this period, weight and mid-arm circumference correlated positively with TG and negatively with HDL. There were positive correlations between TC and albumin levels for 12 mo after commencement of treatment, but otherwise there were no significant or consistent relationships between lipid profiles and total protein losses, dialysate calorie load, or total cal/kg or solute transport. The worsening dyslipidemia associated with CAPD was not associated with aspects of treatment such as glucose load or protein losses. The strongest predictors of worsening lipid profiles were weight gain and preexisting cardiovascular comorbidity.

Adult↗

Cyclosporin A inhibits early mRNA expression of G0/G1 switch gene 2 (G0S2) in cultured human blood mononuclear cells.

Cyclosporin A (CsA) may achieve its immunosuppressive effects by inhibiting the calcium- and calmodulin-dependent phosphatase calcineurin which is required for activation of target genes by members of the NFAT (nuclear factor of activated T cells) transcription factor family. Among these target genes is the gene encoding interleukin-2 (IL2), a cytokine facilitating progression through the G1 phase of the cell cycle. However, IL2 does not reverse CsA inhibition, suggesting that at least one other NFAT-sensitive gene may be involved. The human G0/G1 switch gene, G0S2, has potential NFAT-binding sites in the 5' flank and encodes a small basic potential phosphoprotein of unknown function. Using a sensitive, reverse transcription-polymerase chain reaction (RT-PCR) assay, G0S2 mRNA levels were assayed in cultured blood mononuclear cells. Freshly isolated cells contain high levels of G0S2 mRNA which rapidly decline. This "spontaneous stimulation" is also noted with some other G0S genes and has been attributed to some aspect of the isolation procedure. In cells that have been preincubated to lower mRNA levels, there is a transient increase in G0S2 mRNA, peaking between 1-2 h, in response to Concanavalin-A (ConA), or to the combination of phorbol ester (TPA), and the calcium ionophore, ionomycin. Both these responses are inhibited by CsA. Our results suggest that G0S2 expression is required to commit cells to enter the G1 phase of the cell cycle, and that, while not excluding other possible targets, early inhibition of G0S2 expression by CsA may be important in achieving immunosuppression. G0S2 may be of value as a reporter gene for analyzing the mechanism of action of CsA and its influence on the positive and negative selection of lymphocytes in response to self and not-self antigens.

Amino Acid Sequence↗

Role of lipid hydroperoxides in the activation of 15-lipoxygenase.

We have used stopped-flow rapid reaction methods, employing both fluorescence and absorbance monitoring, together with HPLC analysis of the products to study the activation of soybean 15-lipoxygenase by 13(S)-hydroperoxy-9, 11(E,Z)-octadecadienoic acid (13-HPOD). When lipoxygenase is mixed with an equimolar concentration of 13-HPOD, the enzyme undergoes a rapid change in fluorescence. The rate of the change of fluorescence is dependent on the concentration of the 13-HPOD (k = 6.7 x 10(6) M-1 s-1) and is accompanied by activation of the enzyme. The fluorescence change is not accompanied by any change in the UV absorbance of the 13-HPOD, suggesting no loss of the conjugated diene during enzyme activation, and HPLC analysis of the products of the reaction confirms that the 13-HPOD can be recovered unchanged following this reaction. In the presence of an inhibitor (BWA4C, a hydroxamate inhibitor) that reduces the active-site iron, the 13-HPOD and the inhibitor are destroyed in a peroxidase-like reaction. On the basis of these observations we propose that 13-HPOD binds to the enzyme and facilitates activation of the enzyme, possibly through the formation of a protein radical, and that the 13-HPOD is not changed chemically in this process.

Arachidonate 15-Lipoxygenase↗

Sequence analysis and expression in cultured lymphocytes of the human FOSB gene (G0S3).

G0S3 is a member of a set of putative G0/G1 switch regulatory genes (G0S genes) selected by screening cDNA libraries prepared from human blood mononuclear cells cultured for 2 hr with lectin and cycloheximide. The sequence shows high homology with the murine FOSB gene, which encodes a component of the AP1 transcriptional regulator. Comparison of cDNA and genomic sequences reveals a 4-exon structure characteristic of the FOS family of genes. Freshly isolated cells show high levels of FOSB/G0S3 and FOS/G0S7 mRNAs, which decline rapidly during incubation in culture medium. The kinetics of expression suggest that the high initial levels are caused by the isolation procedure, and do not reflect constitutive expression. In cells preincubated for a day, levels of FOS mRNA reach a maximum 20 min after the addition of lectin and decline to control levels over the next 3 hr. Levels of FOSB mRNA reach a maximum 40 min after the addition of lectin and decline to control levels over the next 6 hr. In freshly isolated cells, both FOS and FOSB mRNAs increase dramatically in response to the protein synthesis inhibitor cycloheximide. In preincubated cells, the cycloheximide response is decreased, especially in the case of FOSB. These differences in expression of FOS and FOSB suggest different roles and regulation. Regions of low base order-dependent stem-loop potential in the region of the gene are defined. These indicate where base order has been adapted for purposes other than stem-loop stability (e.g., encoding proteins or gene regulation). Regions of low potential in a 68.5-kb genomic segment containing the FOSB gene suggest that the potential may help locate genes in uncharted DNA sequences.

Adult↗

Reduction of extraneural scarring by ADCON-T/N after surgical intervention.

The effects of ADCON-T/N (Gliatech, Inc., Cleveland, OH), a carbohydrate polymer gel, on peripheral nerve scarring and regeneration were studied in rodents undergoing three types of surgical intervention. Procedure I involved external neurolysis of the sciatic nerve from surrounding tissues and separation of its tibial and peroneal components. Procedure II involved the addition of an abrasive injury. Procedure III involved transection and suture anastomosis of the tibial component. ADCON-T/N or a control gel was locally applied in a blind fashion. Additional animals received no gel, as a further control. Animals underwent second operations 4 weeks after Procedures I and II and 6 weeks after Procedure III. The surgical sites were evaluated using a numerical grading scheme to assess wound healing, sciatic nerve adherence to surrounding tissues, and separability of its tibial and peroneal components. Animals receiving ADCON-T/N demonstrated reduced nerve adherence to surrounding tissues and enhanced separability of the tibial and peroneal components, compared with animals receiving control gel or no gel. Quantitative histological analysis revealed a statistically significant reduction in the amount of dense scar tissue surrounding nerves treated with ADCON-T/N. No evidence of nerve toxicity caused by ADCON-T/N was noted. Counts of regenerating myelinated axons in animals undergoing nerve transection and suture repair did not statistically differ in treated and untreated animals. In conclusion, ADCON-T/N seems to be both safe and effective in reducing extraneural scar formation after peripheral nerve surgery and local trauma.

Animals↗

Knowledge and practice in pressure area care.

Many nurses do not receive post-basic training on pressure area care. Even when they are knowledgeable on pressure care, nurses do not always implement this knowledge in practice. Computerised care planning appears to improve pressure area care. Qualified nurses need education about the prevention and treatment of pressure sores.

Adult↗

Impact of peritoneal absorption of glucose on appetite, protein catabolism and survival in CAPD patients.

Dietary protein and calorie intake, protein catabolism and peritoneal kinetics were measured in 97 CAPD patients to establish the effect of peritoneal glucose absorption on appetite and survival. There was a large variability in the number of calories obtained from the dialysate, mean 5.89 cal/kg (median 5.43 cal/kg), with a skewed distribution, due to the increased requirement for hypertonic solutions by patients with more rapid glucose absorption and poor ultrafiltration. On average calories derived from peritoneal absorption accounted for 19% of the total energy intake which in itself was well below that recommended. Patients with > 6 cal/kg, obtained from the dialysate (top 20th percentile, n = 19) were compared with those with < 6 cal/kg, but no significant differences in oral protein or calorie intake, protein catabolism or total calorie intake were found. Age, body mass index (BMI) and KT/V were also similar in both groups. Patients were followed-up prospectively for a minimum of 24 months and a comparison made of actuarial survival. Patients with high peritoneal calorie intake tended to survive longer but this was not significantly different (p = 0.25). This study suggests that calories derived from the peritoneum in CAPD patients do not suppress appetite, provide a useful and significant proportion of the total energy intake, that does not cause excessive obesity or have a negative effect on patient survival.

Absorption↗

Comorbidity, urea kinetics, and appetite in continuous ambulatory peritoneal dialysis patients: their interrelationship and prediction of survival.

Comorbidity, urea kinetics (Kt/V and normalized protein catabolic rate), dietary protein, total calorie intake, and plasma albumin were measured in 97 continuous ambulatory peritoneal dialysis patients followed prospectively for 30 months. Comorbid disease was graded severe in 12 patients, intermediate in 29, and absent in 56. At entry to the study comorbidity was associated with increased age (P = 0.001), lower dietary protein (P = 0.015) and calorie intake (P = 0.02), and a lower plasma creatinine (P = 0.026). Trends toward lower Kt/V and albumin were not significant, and normalized protein catabolic rate was unaffected. Ability of these measures to predict mortality was assessed by univariate and multivariate analysis using Cox's proportional hazard model. On univariate analysis, comorbidity (P < 0.0001), age (P = 0.0001), Kt/V (P = 0.009), plasma albumin (P = 0.009), calorie intake (P = 0.035), and dietary protein intake (P = 0.03) predicted outcome, whereas normalized protein catabolic rate did not (P = 0.46). Multivariate analysis indicated that comorbidity (P = 0.0003) and age (P = 0.0085) were the only independent predictors of outcome. The addition of plasma albumin and Kt/V increased the significance of the Cox model. Further analysis of comorbidity demonstrated the relative importance of vascular disease and left ventricular dysfunction. This study illustrates the profound influence of comorbid disease on mortality in continuous ambulatory peritoneal dialysis patients and suggests that it causes suppression of appetite independent of the dialysis dose.

Adolescent↗