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Biomedical subjects

J King

Publications and source records attributed to J King.

At least 55 records · Page 3Linked to original sources

Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review.

OBJECTIVE: To assess the effectiveness and safety of antiplatelet drugs for prevention of pre-eclampsia and its consequences. DESIGN: Systematic review. DATA SOURCES: Register of trials maintained by Cochrane Pregnancy and Childbirth Group, Cochrane Controlled Trials Register, and Embase. INCLUDED STUDIES: Randomised trials involving women at risk of pre-eclampsia, and its complications, allocated to antiplatelet drug(s) versus placebo or no antiplatelet drug. MAIN OUTCOME MEASURES: Pre-eclampsia, preterm birth, fetal or neonatal death, and small for gestational age baby. Studies were assessed for quality of concealment of allocation and losses to follow up. RESULTS: 39 trials (30 563 women) were included, and 45 trials (>3000 women) excluded. Use of antiplatelet drugs was associated with a 15% reduction in the risk of pre-eclampsia (32 trials, 29 331 women; relative risk 0.85, 95% confidence interval 0.78 to 0.92; number needed to treat 100, 59 to 167). There was also an 8% reduction in the risk of preterm birth (23 trials, 28 268 women; 0.92, 0.88 to 0.97; 72, 44 to 200), and a 14% reduction in the risk of fetal or neonatal death (30 trials, 30 093 women; 0.86, 0.75 to 0.98; 250, 125 to >10 000) for women allocated antiplatelet drugs. Small for gestational age babies were reported in 25 trials (20 349 women), with no overall difference between the groups (relative risk 0.92, 0.84 to 1.01). There were no significant differences in other measures of outcome. CONCLUSIONS: Antiplatelet drugs, largely low dose aspirin, have small to moderate benefits when used for prevention of pre-eclampsia.

Aspirin↗

Reduction in recurrence risk for involved or inadequate margins with edge cryotherapy after liver resection for colorectal metastases.

HYPOTHESIS: The usefulness of additional edge cryotherapy after liver resection for liver metastases from colorectal cancer to improve involved or inadequate (less than 1 cm) margins is uncertain. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Department of surgery at a university hospital. PATIENTS: Eighty-six consecutive patients with hepatic metastases from colorectal cancer in whom we applied additional edge cryotherapy to involved or inadequate margins. This group was compared with 134 patients who underwent resection without edge cryotherapy (control group) during the same period. INTERVENTION: Potentially curative treatment was achieved by adding edge cryotherapy to insufficient resection sites in patients not eligible for further resection. MAIN OUTCOME MEASURES: Edge recurrence rate in the study group; validation of an additional treatment to improve curative resectability; and comparison of morbidity and local recurrence rates with the control group. RESULTS: At a median follow-up of 39 months, 47 patients were alive and 39 had died. Local recurrence at the resection site was diagnosed in 9 patients (10%), of which 7 occurred in patients with involved margins and 2 in patients with resection margin less than 1 cm. Thirty-six patients (42%) experienced recurrence in the remnant liver. Extrahepatic recurrence occurred in 38 patients (44%), the lungs being the most common site (22 patients [26%]). CONCLUSIONS: Edge cryotherapy is a potent additional surgical treatment option in patients with liver metastases from colorectal cancer. The percentage of patients who can be treated for cure can be increased, especially if complex liver surgery is demanded.

Adult↗

Alternate splicing at the 3'-end of the human pancreatic tumor-associated mucin MUC4 cDNA.

MUC4 is a membrane-bound mucin and is considered as the human homologue of the rat sialomucin complex (SMC). The deduced structural organization of the wild type-MUC4 cDNA (WT-MUC4) sequence revealed two subunits: a large amino mucin type subunit (MUC4alpha) and a transmembrane subunit (MUC4beta). MUC4beta is a membrane-bound growth factor like subunit and contains three EGF-like domains. The MUC4 gene is expressed in several normal tissues like trachea, lung, and testis. It is not expressed in a normal human pancreas; however, its dysregulation results in high levels of expression in pancreatic tumors and tumor cell lines. Recently, we have demonstrated the presence of alternative splice events in the 3'-end of the MUC4 cDNA that generated new putative variants (sv1-sv10) in normal human testis and in a pancreatic tumor cell line (HPAF). In search of MUC4 variant(s) that are specific to pancreatic adenocarcinoma, we investigated the splicing phenomena in the MUC4 cDNA sequence by using a large panel of pancreatic tumor cell lines. We have identified ten alternative splice events located downstream to the central large tandem repeat domain. These splice events generated 12 variant species (sv4, sv9, sv10-18, and sv21) of MUC4 cDNAs. The deduced amino acid sequence of these variant MUC4 cDNAs revealed two distinct types: a family of secreted and a membrane-associated variant form. Among the members of MUC4 secreted variant family, three (sv4, sv12, and sv13) of ten showed a short 144 residue COOH-terminus compared to 1154 residues in WT-MUC4. The variants with this short COOH-terminus (144 residues) was found in 37% (4/11) of the tumor lines. The putative membrane-bound variant sv10 was detected in 37% (4/11) pancreatic tumor cell lines but not in any normal human tissues. In conclusion, we have identified novel splice variant(s) of MUC4 in pancreatic adenocarcinoma.

3' Untranslated Regions↗

Growth inhibition of glioblastoma cells by human Pur(alpha).

Pur(alpha) is a multifunctional DNA- and RNA-binding protein implicated in a variety of biological events including transcription and replication. Further, this protein has the ability to form a complex with several cellular proteins which are important for cell proliferation including the transcription factor, E2F-1. Pur(alpha) has a modular structure highlighted by alternating three basic aromatic class I and two acidic leucine-rich class II repeats in the central region of the protein. Here, we demonstrate that ectopic overexpression of Pur(alpha) suppresses proliferation of a variety of transformed and tumor cells including human glioblastoma. By utilizing various deletion mutants of Pur(alpha) in colony formation assay, we identified the region spanning the first class II repeat (residues 107-131) and the second class I repeat (residues 148-170) of Pur(alpha) which participate in growth inhibitory action of Pur(alpha). Results from protein transduction experiments using the synthetic peptides representing residues 109-131 and 123-154 of Pur(alpha) in fusion with the arginine rich domain of HIV-1 Tat revealed cellular internalization and nuclear appearance of the Tat-Pur(alpha) fusion peptide after 2 h and its detection in nuclei up to 24 h after treatment. Glioblastoma cells treated with Tat-Pur(alpha) (109-131) and Tat-Pur(alpha) (123-154) exhibited 41 and 47% decrease, respectively, in proliferation. Altogether these results illustrate the efficacy of Pur(alpha) in suppressing glioblastoma cell growth and provide evidence for the potential use of this protein and its derivative(s) in blocking proliferation of tumor cells.

Active Transport, Cell Nucleus↗

Popular diets: correlation to health, nutrition, and obesity.

OBJECTIVE: To examine the association between a range of health and nutrition indicators and popular diets. DESIGN: The Continuing Survey of Food Intake by Individuals (CSFII) 1994-1996 data were used to examine the relationship between prototype popular diets and diet quality as measured by the healthy eating index (HEI), consumption patterns, and body mass index (BMI). The prototype diets included vegetarian (no meat, poultry, or fish on day of survey) and non-vegetarian. The nonvegetarian group was further subdivided into low carbohydrate (less than 30% of energy from carbohydrate), medium (30% to 55%), and high (greater than 55% of energy). Within the high carbohydrate group, participants were classified as having Pyramid or non-Pyramid eating patterns. The Pyramid group was defined as 30% or less of energy from fat and at least one serving from the five major food groups in the USDA Food Guide Pyramid. Finally, the non-Pyramid group was further subdivided into low fat (less than 15% of energy from fat) and moderate fat (15% to 30% of energy from fat). In addition, a review of the published scientific literature was conducted; all studies identified were included in the review. SUBJECTS: 10,014 adults, aged 19 years and older, from the 1994-1996 CSFII were included in the analyses of extant data. More than 200 individual studies were included in the review of the literature. RESULTS: Analyses of the CSFII indicate that diet quality as measured by HEI was highest for the high carbohydrate Pyramid group (82.9) and lowest for the low carbohydrate group (44.6). Energy intakes were low for the vegetarians (1,606 kcals) and high carbohydrate/low fat group (1360 kcals). BMIs were lowest for women in the vegetarian group (24.6) and the high carbohydrate/low fat group (24.4); for men, the lowest BMIs were observed for vegetarians (25.2) and the high carbohydrate Pyramid group (25.2). Review of the literature suggests that weight loss is independent of diet composition. Energy restriction is the key variable associated with weight reduction in the short term. CONCLUSIONS: Diets that are high in carbohydrate and low to moderate in fat tend to be lower in energy. The lowest energy intakes were observed for those on a vegetarian diet. The diet quality as measured by HEI was highest for the high carbohydrate groups and lowest for the low carbohydrate groups. The BMIs were significantly lower for men and women on the high carbohydrate diet; the highest BMIs were noted for those on a low carbohydrate diet.

Adult↗

Development and evaluation of a real-time quantitative PCR for the detection of human cytomegalovirus.

A novel real-time quantitative PCR (QPCR) assay is described for monitoring CMV DNA load in clinical specimens using the LightCycler. The assay is rapid (< 40 min), easy to carry out, robust, reliable and is capable of detecting from 10 to over 2 x 10(5) CMV DNA copies with a wide linear range. Amplification and detection occur simultaneously, avoiding the need for post-PCR analysis and thereby minimising the risk of carryover contamination. The assay proved to be accurate, specific and reproducible when evaluated in three different laboratories. In addition, LightCycler results were comparable with those of TaqMan, an independent real-time QPCR assay.

Cytomegalovirus↗

Children with sialorrhoea in the absence of neurological abnormalities.

OBJECTIVE: To study the outcome of 21 typically developing children who had been referred to the Saliva Control Clinic at the Royal Children's Hospital, Melbourne. METHOD: Information was collected on various aspects of the child's health, oromotor function and severity of drooling. A follow-up telephone survey was completed by the parents of these children after a mean period of 3.4 years. Information was gathered regarding their child's drooling, current health, oromotor status and the usefulness of the clinic. RESULTS: There was a statistically significant improvement (P < 0.01) in the saliva control measures analysed on follow-up. Thirteen children ceased to drool, three still drooled occasionally, and five continued to drool. The recommendations, mainly advice and referrals to other health professionals, were generally reported to be helpful by the parents. CONCLUSIONS: This cohort of children was established retrospectively, and the study is therefore limited in both numbers and design. The results indicate that some typically developing children may be delayed in the development of saliva control. Parents and professionals can be reassured that this problem is likely to resolve.

Child↗

Development of a self-directed learning readiness scale for nursing education.

Self-directed learning is a method of instruction used increasingly in adult education. A scale was developed in response to a need for a valid and reliable instrument to measure self-directed learning readiness. Such a scale will allow nurse educators to diagnose students' attitudes, abilities and personality characteristics, necessary for self-directed learning. This study was undertaken in two stages. In the first, the Delphi technique utilizing a panel of 11 nurse educator experts was used to assess the content and construct validity of a number of items perceived to reflect self-directed learning readiness. Each panel member was asked to independently rate the relevance of each item on a Likert scale. The second stage involved the administration of the questionnaire to a convenience sample of 201 undergraduate nursing students. The questionnaire was analysed using principal components factor analysis with varimax rotation, Chronbach's coefficient alpha, and item-to-total correlations to measure the scale's construct validity, internal consistency (reliability), and unidimensionality, respectively.The resulting self-directed learning readiness scale appears homogeneous and valid. The scale will assist nurse educators in the diagnosis of student learning needs, in order for the educator to implement teaching strategies that will best suit the students. Furthermore the development of this scale will provide valuable data for curriculum development.

Attitude of Health Personnel↗

The reliability of the SCAN test: results from a primary school population in the UK.

The SCAN test utilizes a pre-recorded tape, with carrier phrase and target words spoken by an American English speaker, to screen for central auditory processing disorders in children. The aim of the present study was to establish whether the normative data, derived from American school children, are applicable to a UK primary school population. The SCAN test was administered to 133 British primary school children with normal hearing, stratified into one-year age bands. Mean scores from the UK sample were found to be significantly lower than US mean scores for the most of the age bands. Analysis of word errors indicates accent and word familiarity effects. This evaluation of the SCAN indicates that the test is not directly applicable to British children as currently normalized. The present study provides interim norms for the American recording for age bands six to 11 years. It is recommended that the test material is recorded by a UK English speaker, with substitution of high error-rate target words, followed by normative data collection for the new test material.

Child↗

Phycobiliprotein genes of the marine photosynthetic prokaryote Prochlorococcus: evidence for rapid evolution of genetic heterogeneity.

Prochlorococcus is a major photosynthetic prokaryote in nutrient-limited, open ocean environments and an important participant in the global carbon cycle. This phototroph is distinct from other members of the cyanobacterial lineage to which it belongs because it utilizes a chlorophyll a2/b(2) light-harvesting complex as its major antenna, instead of phycobilisomes. Recently, genes encoding the phycobiliprotein phycoerythrin were identified in several Prochlorococcus isolates, thus making it the only extant photosynthetic prokaryote to possess a chlorophyll a/b antenna as well as phycobiliprotein genes. In order to understand the evolution of phycobiliproteins in this genus, the authors have sequenced the phycoerythrin genes of two isolates that are the most deeply branching in the Prochlorococcus lineage and share the highest degree of 16S rDNA sequence similarity to phycobilisome-containing marine SYNECHOCOCCUS: Sequence analyses suggest that within the Prochlorococcus lineage, the selective forces shaping the evolution of the phycoerythrin gene set have not been uniform. Although strains that are most closely related to marine Synechococcus possess genes (cpeB, cpeA) encoding both subunits of phycoerythrin, a more recently evolved strain is shown to lack cpeA and to possess a degenerate form of cpeB. Differences in phycoerythrin gene sequences between Prochlorococcus and Synechococcus appear to be consistent with a model of elevated mutation rates rather than relaxed selection. This suggests that although phycoerythrin is not a major constituent of the light-harvesting apparatus in Prochlorococcus, as it is in Synechococcus, the cpeB and cpeA genes are still under selection, albeit a different type of selection than in Synechococcus. The evolution of the Prochlorococcus light-harvesting antenna complex provides an important system for understanding the origins and scope of phylogenetic diversity in ocean ecosystems.

Amino Acid Sequence↗

Whole proteome pI values correlate with subcellular localizations of proteins for organisms within the three domains of life.

Isoelectric point (pI) values have long been a standard measure for distinguishing between proteins. This article analyzes distributions of pI values estimated computationally for all predicted ORFs in a selection of fully sequenced genomes. Histograms of pI values confirm the bimodality that has been observed previously for bacterial and archaeal genomes () and reveal a trimodality in eukaryotic genomes. A similar analysis on subsets of a nonredundant protein sequence database generated from the full database by selecting on subcellular localization shows that sequences annotated as corresponding to cytosolic and integral membrane proteins have pI distributions that appear to correspond with the two observed modes of bacteria and archaea. Furthermore, nuclear proteins have a broader distribution that may account for the third mode observed in eukaryotes. On the basis of this association between pI and subcellular localization, we conclude that the bimodal character of whole proteome pI values in bacteria and archaea and the trimodal character in eukaryotes are likely to be general properties of proteomes and are associated with the need for different pI values depending on subcellular localization. Our analyses also suggest that the proportions of proteomes consisting of membrane-associated proteins may be currently underestimated.

Animals↗

Frequencies of amino acid strings in globular protein sequences indicate suppression of blocks of consecutive hydrophobic residues.

Patterns of hydrophobic and hydrophilic residues play a major role in protein folding and function. Long, predominantly hydrophobic strings of 20-22 amino acids each are associated with transmembrane helices and have been used to identify such sequences. Much less attention has been paid to hydrophobic sequences within globular proteins. In prior work on computer simulations of the competition between on-pathway folding and off-pathway aggregate formation, we found that long sequences of consecutive hydrophobic residues promoted aggregation within the model, even controlling for overall hydrophobic content. We report here on an analysis of the frequencies of different lengths of contiguous blocks of hydrophobic residues in a database of amino acid sequences of proteins of known structure. Sequences of three or more consecutive hydrophobic residues are found to be significantly less common in actual globular proteins than would be predicted if residues were selected independently. The result may reflect selection against long blocks of hydrophobic residues within globular proteins relative to what would be expected if residue hydrophobicities were independent of those of nearby residues in the sequence.

Alkyl and Aryl Transferases↗

Role for cysteine residues in the in vivo folding and assembly of the phage P22 tailspike.

The predominantly beta-sheet phage P22 tailspike adhesin contains eight reduced cysteines per 666 residue chain, which are buried and unreactive in the native trimer. In the pathway to the native trimer, both in vivo and in vitro transient interchain disulfide bonds are formed and reduced. This occurs in the protrimer, an intermediate in the formation of the interdigitated beta-sheets of the trimeric tailspike. Each of the eight cysteines was replaced with serine by site-specific mutagenesis of the cloned P22 tailspike gene and the mutant genes expressed in Escherichia coli. Although the yields of native-like Cys>Ser proteins varied, sufficient soluble trimeric forms of each of the eight mutants accumulated to permit purification. All eight single Cys>Ser mature proteins maintained the high thermostability of the wild type, as well as the wild-type biological activity in forming infectious virions. Thus, these cysteine thiols are not required for the stability or activity of the native state. When their in vivo folding and assembly kinetics were examined, six of the mutant substitutions--C267S, C287S, C458S, C613S, and C635S--were significantly impaired at higher temperatures. Four--C290S, C496, C613S, and C635--showed significantly impaired kinetics even at lower temperatures. The in vivo folding of the C613S/C635S double mutant was severely defective independent of temperature. Since the trimeric states of the single Cys>Ser substituted chains were as stable and active as wild type, the impairment of tailspike maturation presumably reflects problems in the in vivo folding or assembly pathways. The formation or reduction of the transient interchain disulfide bonds in the protrimer may be the locus of these kinetic functions.

Adhesins, Bacterial↗

Student learning through video assessment.

This paper reports on the use of video and self-assessment as a tool to guide and support undergraduate students in the practice of nursing. This method of learning and assessment promoted self- and peer evaluation as well as critical thinking. It encouraged students to take more responsibility for their learning and assisted academic staff and students to identify learning issues associated with clinical practices. Evaluative comments by teachers, students and educational experts have established the credibility and continued use of this approach within the Bachelor of Nursing program at a major university in Sydney, Australia.

Education, Nursing, Baccalaureate↗

Fetal valproate syndrome and autism: additional evidence of an association.

Autism has been described in association with a variety of medical and genetic conditions. We previously reported on a patient whose clinical phenotype was compatible with both fetal valproate syndrome (FVS) and autism. Here we present five additional patients with FVS and autism. In all five of our patients, there was evidence of cognitive deficits, manifestations of autism, and typical phenotypic characteristics of FVS. The association between this known teratogen and autism has both clinical and research implications.

Autistic Disorder↗

Carbon and complex nitrogen source selection for secondary metabolite cultivation at the pilot scale.

The fermentation of desmethyl-asterriquinone B-1, a diabetes target, by a Pseudomonasarias species was conducted at the 600-l scale using a revised complex medium containing yeast extract and soy hydrolysate. Oat flour and tomato paste were removed from this medium due to difficulties in sterilization. An initial cerelose charge of 40 g/l improved titer and reduced product degradation in the broth at cultivation conditions. An initial mannitol concentration of 65 g/l effectively avoided mid-cycle mannitol additions necessary for the 40 g/l mannitol concentration without the reduction in productivity seen at 90 g/l mannitol. These additions diluted the broth because of the low aqueous solubility of mannitol. Titers reached 3.0 g/l after 158 h with an optimized process, increasing two-fold from the original medium and operating conditions. Reproducible foaming occurred at the point of glucose exhaustion when the culture switched to mannitol consumption. Use of alternative carbon sources (glycerol, soybean oil, sorbitol in conjunction with cerelose) was not effective in attaining similar productivity and did not reduce the extent of foaming. In the case of fructose, the extent of foaming was markedly reduced but product formation was negligible.

Journal Article↗

Immunization of humans with recombinant pneumococcal surface protein A (rPspA) elicits antibodies that passively protect mice from fatal infection with Streptococcus pneumoniae bearing heterologous PspA.

Pneumococcal surface protein A (PspA), a cross-reactive protein expressed by all pneumococci, is known to elicit an antibody in animals that can passively protect mice from infection with Streptococcus pneumoniae. A phase I trial with recombinant PspA showed the protein to be immunogenic in humans. Pre- and postimmune serum samples from this trial were examined, and human antibody to PspA could protect mice from pneumococcal infection. The serum samples of subjects immunized twice with 125 microg of PspA had >100 times as much antibody per milliliter as was required to consistently protect mice from fatal infection (1.3 microg/dose). At least 98% of PspAs fall into PspA sequence/serologic families 1 or 2. Human antibodies elicited by a family 1 PspA protected against infection with S. pneumoniae expressing either family 1 or 2 PspAs and with strains of all 3 capsular types tested: 3, 6A, and 6B. These studies suggest that PspA may have efficacy as a human vaccine.

Adult↗