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Biomedical subjects

J Field

Publications and source records attributed to J Field.

At least 37 records · Page 2Linked to original sources
PubMed2001

Delayed diagnosis of cardiac tamponade following isolated blunt abdominal trauma.

Traumatic haemopericardium is an uncommon but life threatening condition. It is usually caused by penetrating cardiac injuries or cardiac rupture from blunt chest trauma. We report haemopericardium and cardiac tamponade in a young girl after blunt abdominal trauma. She presented with mild upper abdominal pain, tachycardia and hypotension having been kicked in the abdomen by a horse. No damage was found at laparotomy and she remained haemodynamically unstable. Further investigation found cardiac tamponade and haemopericardium. This was managed by insertion of a pericardial drain using transthoracic echocardiogram guidance, with later drainage in the operating theatre using guidance with a transoesophageal echocardiogram.

Abdominal Injuries↗
PubMed2001

The acceptability of urinary LCR testing for Chlamydia trachomatis among participants in a probability sample survey of sexual attitudes and lifestyles.

OBJECTIVES: To examine the factors that influence respondents' willingness to participate in urinary testing for Chlamydia trachomatis in a general population feasibility survey of sexual attitudes and lifestyles. METHODS: 199 sexually experienced, 18-44 year old participants, recruited as part of a larger (n=901) methodological study of sexual attitudes and lifestyles, were invited to provide a urine sample for chlamydial infection testing using ligase chain reaction (LCR) techniques. Analysis of the survey data and in-depth qualitative interviews were undertaken to explore the factors that influenced participants' decisions to participate. RESULTS: 143/199 (72%) participants agreed to provide a urine sample. The likelihood of providing a urine sample was reduced if other individuals were present in the home at the time of interview (OR 0.42, 95% confidence interval 0.20-0.90, p=0.03). Trust and rapport with the interviewer, understanding the aims of the test, sense of obligation, and perceived importance of the test were identified as additional influencing factors in the in-depth interviews. CONCLUSIONS: Survey respondents' uncertainty or embarrassment at participating in urine testing can be overcome if they are well informed, motivated by the potential health gain, and briefed by trained and confident interviewers.

Adolescent↗
PubMed2000

Insurance-based advantage to helpers in a tropical hover wasp.

The origin and maintenance of eusociality is a central problem in evolutionary biology. Eusocial groups contain individuals that forfeit their own reproduction in order to help others reproduce. In facultatively eusocial taxa, offspring can choose whether to found new nests or become helpers in their natal groups. In many facultatively eusocial insects, offspring need continuous care during development, but adult carers have life expectancies shorter than the developmental period. When a lone foundress dies, her partly reared brood are usually doomed. Here, we show that helpers in a tropical hover wasp (Liostenogaster flavolineata) have an insurance-based advantage over lone foundresses because after a helper dies, most of the brood that she has partly reared will be brought to maturity by surviving nest-mates. After some of the helpers are experimentally removed from a multi-female nest, the reduced group is left with more brood than it would normally rear. We found that larger, more valuable extra brood were reared through to maturity, but not smaller, less valuable brood. Smaller brood may be sacrificed to feed larger brood, and reduced groups probably benefited from increased short-term helper recruitment. Rearing extra brood did not increase adult mortality or brood development time.

Animals↗
PubMed2000

The Akt proto-oncogene links Ras to Pak and cell survival signals.

The Ras oncogene regulates cellular proliferation, differentiation, transformation, and survival through multiple downstream signals. Ras signals through its effector phosphoinositide 3 (PI3) kinase to the Pak protein kinase (p65(pak)), but the steps from Ras to Pak remain to be elucidated. PI3 kinase can stimulate the small G protein, Rac, a direct activator of Pak, as well as the Akt proto-oncogene, a serine-threonine protein kinase. We found that activated Akt stimulated Pak, whereas a dominant negative Akt inhibited Ras activation of Pak in transfection assays. Akt stimulation of Pak was not inhibited by dominant negative mutants of either Rac or Cdc42 suggesting that Akt activated Pak through a GTPase-independent mechanism. We also developed a novel cell-free system to study Ras activation of Pak. In this system Ras activated Pak only in the presence of a crude cell extract but failed to activate Pak when Akt was immunodepleted from the extract. Akt protects cells from apoptosis through phosphorylation of downstream targets such as the Bcl-2 family member, Bad. We found that activated Pak decreased apoptosis and increased phosphorylation of Bad, whereas dominant negative Pak increased apoptosis and decreased phosphorylation of Bad. These studies define a new oncogene-mediated cell survival signal.

Animals↗
PubMed2000

Constitutive and inducible expression of hepatic CYP2E1 in leptin-deficient ob/ob mice.

In this study we have analyzed the inducible as well as constitutive hepatic expression of Cyp2e1 in a genetic model of obesity and non-insulin dependent (type II) diabetes, the leptin-deficient ob/ob mouse. In obese mice, Cyp2e1 levels were decreased compared to lean littermates. Treatment with leptin increased hepatic Cyp2e1 in obese mice to the levels observed in lean animals, but failed to alter Cyp2e1 expression in lean animals. As expected, leptin also reduced food intake in treated mice compared to saline-treated controls. In obese mice pair-fed the reduced amount of food, there was a significant increase in Cyp2e1 mRNA but no increase in Cyp2e1 protein or enzyme activity. Fasting and administration of acetone and 4-methylpyrazole increased Cyp2e1 mRNA as well as protein and activity in both obese and lean mice. The present data indicate that while Cyp2e1 is still inducible in obese mice by xenobiotics and fasting, full constitutive expression of Cyp2e1 requires leptin to be present. This effect of leptin appears to be at least partly independent of the hypothalamic control of food intake.

Acetone↗
PubMed2000

Mammalian homolog of the yeast cyclase associated protein, CAP/Srv2p, regulates actin filament assembly.

Control of cell shape and motility requires rearrangements of the actin cytoskeleton. One cytoskeletal protein that may regulate actin dynamics is CAP (cyclase associated protein; CAP/Srv2p; ASP-56). CAP was first isolated from yeast as an adenylyl cyclase associated protein required for RAS regulation of cAMP signaling. In addition, CAP also regulates the actin cytoskeleton primarily through an actin monomer binding activity. CAP homologs are found in many eukaryotes, including mammals where they also bind actin, but little is known about their biological function. We, therefore, designed experiments to address CAP1 regulation of the actin cytoskeleton. CAP1 localized to membrane ruffles and actin stress fibers in fixed cells of various types. To address localization in living cells, we constructed GFP-CAP1 fusion proteins and found that fusion proteins lacking the actin-binding region localized like the wild type protein. We also performed microinjection studies with affinity-purified anti-CAP1 antibodies in Swiss 3T3 fibroblasts and found that the antibodies attenuated serum stimulation of stress fibers. Finally, CAP1 purified from platelets through a monoclonal antibody affinity purification step stimulated the formation of stress fiber-like filaments when it was microinjected into serum-starved Swiss 3T3 cells. Taken together, these data suggest that CAP1 promotes assembly of the actin cytoskeleton.

3T3 Cells↗
PubMed2000

Early lateral transfer of genes encoding malic enzyme, acetyl-CoA synthetase and alcohol dehydrogenases from anaerobic prokaryotes to Entamoeba histolytica.

The fermentation enzymes, which enable the microaerophilic protist Entamoeba histolytica to parasitize the colonic lumen and tissue abscesses, closely resemble homologues in anaerobic prokaryotes. Here, genes encoding malic enzyme and acetyl-CoA synthetase (nucleoside diphosphate forming) were cloned from E. histolytica, and their evolutionary origins, as well as those encoding two alcohol dehydrogenases (ADHE and ADH1), were inferred by means of phylogenetic reconstruction. The E. histolytica malic enzyme, which decarboxylates malate to pyruvate, closely resembles that of the archaeon Archaeoglobus fulgidus, strongly suggesting a common origin. The E. histolytica acetyl-CoA synthetase, which converts acetyl-CoA to acetate with the production of ATP, appeared to be closely related to the Plasmodium falciparum enzyme, but it was no more closely related to the Giardia lamblia acetyl-CoA synthetase than to those of archaea. Phylogenetic analyses suggested that the adh1 and adhe genes of E. histolytica and Gram-positive eubacteria share a common ancestor. Lateral transfer of genes encoding these fermentation enzymes from archaea or eubacteria to E. histolytica probably occurred early, because the sequences of the amoebic enzymes show considerable divergence from those of prokaryotes, and the amoebic genes encoding these enzymes are in the AT-rich codon usage of the parasite.

Acetate-CoA Ligase↗
PubMed2000

Aprotinin (Trasylol) does not reduce bleeding in primary total hip arthroplasty.

This is a randomized, double-blind, controlled study of the effects of aprotinin (Trasylol) during primary total hip arthroplasty. Sixty patients were randomized to receive either 1.5 x 10(6) KIU of aprotinin or a similar volume of normal saline as a bolus preoperatively. Blood loss was measured from the femoral canal at the time of surgery. An estimate of the total blood loss during the operation was made, and the transfusion requirement was recorded. There was no significant difference between the groups in terms of total blood loss, postoperative hemoglobin, or transfusion requirement. In the group that received aprotinin, there was a trend toward reduced blood loss from the femoral canal, but this was not statistically significant. The results of this study do not support the routine use of aprotinin in primary total hip arthroplasty.

Aged↗
PubMed2000

Does splintage help pain after carpal tunnel release?

A prospective randomized single blind trial was performed of 102 patients undergoing carpal tunnel release. Patients received either a palmar plaster of Paris splint or a bulky wool and crepe bandage postoperatively for the first 48 h, to determine whether the plaster slab reduced postoperative pain. There were no statistically significant differences between the two groups in postoperative pain scores or analgesic use.

Carpal Tunnel Syndrome↗
PubMed2000

The most abundant glycoprotein of amebic cyst walls (Jacob) is a lectin with five Cys-rich, chitin-binding domains.

The infectious stage of amebae is the chitin-walled cyst, which is resistant to stomach acids. In this study an extraordinarily abundant, encystation-specific glycoprotein (Jacob) was identified on two-dimensional protein gels of cyst walls purified from Entamoeba invadens. Jacob, which was acidic and had an apparent molecular mass of approximately 100 kDa, contained sugars that bound to concanavalin A and ricin. The jacob gene encoded a 45-kDa protein with a ladder-like series of five Cys-rich domains. These Cys-rich domains were reminiscent of but not homologous to the Cys-rich chitin-binding domains of insect chitinases and peritrophic matrix proteins that surround the food bolus in the insect gut. Jacob bound purified chitin and chitin remaining in sodium dodecyl sulfate-treated cyst walls. Conversely, the E. histolytica plasma membrane Gal/GalNAc lectin bound sugars of intact cyst walls and purified Jacob. In the presence of galactose, E. invadens formed wall-less cysts, which were quadranucleate and contained Jacob and chitinase (another encystation-specific protein) in secretory vesicles. A galactose lectin was found to be present on the surface of wall-less cysts, which phagocytosed bacteria and mucin-coated beads. These results suggest that the E. invadens cyst wall forms when the plasma membrane galactose lectin binds sugars on Jacob, which in turn binds chitin via its five chitin-binding domains.

Amino Acid Sequence↗
PubMed2000

CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) and alcoholic liver disease have similar pathological features. Because CYP2E1 plays a key role in alcoholic liver disease with its ability to stimulate lipid peroxidation, we tested the proposal that CYP2E1 could also be a factor in the development of NASH. In a dietary model - mice fed a methionine- and choline-deficient (MCD) diet - liver injury was associated with both induction of CYP2E1 and a 100-fold increase in hepatic content of lipid peroxides. Microsomal NADPH-dependent lipid oxidases contributed to the formation of these lipid peroxides, and in vitro inhibition studies demonstrated that CYP2E1 was the major catalyst. To further define the role of CYP2E1 as an initiator of oxidative stress in NASH, Cyp2e1(-/-)mice were administered the MCD diet. CYP2E1 deficiency neither prevented the development of NASH nor abrogated the increased microsomal NADPH-dependent lipid peroxidation, indicating the operation of a non-CYP2E1 peroxidase pathway. In Cyp2e1(-/-) mice with NASH (but not in wild-type mice), CYP4A10 and CYP4A14 were upregulated. Furthermore, hepatic microsomal lipid peroxidation was substantially inhibited by anti-mouse CYP4A10 antibody in vitro. These results show that experimental NASH is strongly associated with hepatic microsomal lipid peroxidation. CYP2E1, the main enzyme associated with that process in wild-type mice, is not unique among P450 proteins in catalyzing peroxidation of endogenous lipids. We have now identified CYP4A enzymes as alternative initiators of oxidative stress in the liver.

Animals↗
PubMed2000

Nutrition in the elderly hospital patient Nottingham studies.

Forty percent of elderly hospital admissions in the UK are undernourished, half severely so. Most continue to lose weight in hospital. not only because of disease, but also because of failure to identify and treat malnutrition and due to shortcomings in hospital food provision, upon which most patients depend for their nutritional care. Our studies have shown that more than 40% of food set before patients is left, and therefore wasted. This means that elderly patients are taking less than 70% of their energy (30-35 kcal/kg/day), and protein (1 dram/kg/day) requirements. Catering strategies, such as provision of smaller volume, high energy and protein density meals with snacks and, if necessary, proprietary oral supplements, have been shown not only to improve nutritional status of patients, but to result in improved clinical outcome. Our work has shown a relationship between malnutrition and loss of thermoregulation, which is reversed by appropriate feeding. We have also described the beneficial effects of overnight nasogastric tube feeding in undernourished patients with fractured femur. Like others, we have used a percutaneous endoscopic gastrostomy in the management of elderly patients with cerebrovascular and motor neurone disease, and have published audits of outcome in this field.

Aged↗
PubMed1999

A cytoskeletal localizing domain in the cyclase-associated protein, CAP/Srv2p, regulates access to a distant SH3-binding site.

In the yeast, Saccharomyces cerevisiae, adenylyl cyclase consists of a 200-kDa catalytic subunit (CYR1) and a 70-kDa subunit (CAP/SRV2). CAP/Srv2p assists the small G protein Ras to activate adenylyl cyclase. CAP also regulates the cytoskeleton through an actin sequestering activity and is directed to cortical actin patches by a proline-rich SH3-binding site (P2). In this report we analyze the role of the actin cytoskeleton in Ras/cAMP signaling. Two alleles of CAP, L16P(Srv2) and R19T (SupC), first isolated in genetic screens for mutants that attenuate cAMP levels, reduced adenylyl cyclase binding, and cortical actin patch localization. A third mutation, L27F, also failed to localize but showed no loss of either cAMP signaling or adenylyl cyclase binding. However, all three N-terminal mutations reduced CAP-CAP multimer formation and SH3 domain binding, although the SH3-binding site is about 350 amino acids away. Finally, disruption of the actin cytoskeleton with latrunculin-A did not affect the cAMP phenotypes of the hyperactive Ras2(Val19) allele. These data identify a novel region of CAP that controls access to the SH3-binding site and demonstrate that cytoskeletal localization of CAP or an intact cytoskeleton per se is not necessary for cAMP signaling.

Actins↗