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Biomedical subjects

J King

Publications and source records attributed to J King.

At least 37 records · Page 2Linked to original sources
PubMed2002

Antibiotics for prelabour rupture of membranes at or near term.

BACKGROUND: Prelabour rupture of the membranes at or near term (term PROM) increases the risk of infection for the woman and her baby. The routine use of antibiotics for women at the time of term PROM may reduce this risk. However, due to increasing problems with bacterial resistance and the risk of maternal anaphylaxis with antibiotic use, it is important to assess the evidence addressing risks and benefits in order to ensure judicious use of antibiotics. This review was undertaken to assess the balance of risks and benefits to the mother and infant of antibiotic prophylaxis for prelabour rupture of the membranes at or near term. OBJECTIVES: To assess the effects of antibiotics administered prophylactically to women with prelabour rupture of the membranes at 36 weeks or beyond, on maternal, fetal and neonatal outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's specialised register of controlled trials (October 2001), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001), MEDLINE (1965 to 2001). Other sources included contacting recognised experts and cross referencing relevant material. SELECTION CRITERIA: All randomised trials which compared outcomes for women and infants when antibiotics were administered prophylactically for prelabour rupture of the membranes at or near term, with outcomes for controls (placebo or no treatment). DATA COLLECTION AND ANALYSIS: Assessment of trial quality and data extraction were undertaken independently by the two authors who then compared and resolved differences. Additional data were received from the investigators of included trials. Meta-analysis was undertaken using a fixed effects model and results are presented using relative risk (RR), risk difference (RD) and number needed to treat (NNT) (where appropriate) for categorical data, and mean difference (MD) for variables measured on a continuous scale. All results are presented with 95% confidence intervals (CI). MAIN RESULTS: The results of two trials, involving a total of 838 women, are included in this review. The use of antibiotics resulted in a statistically significant reduction in maternal infectious morbidity (chorioamnionitis or endometritis): RR 0.43 (95% CI 0.23, 0.82), RD -4% (95% CI -7%, -1%), NNT 25 (95% CI 14 -100). No statistically significant differences were shown for outcomes of neonatal morbidity. REVIEWER'S CONCLUSIONS: No clear practice recommendations can be drawn from the results of this review on this clinically important question, related to a paucity of reliable data. Further well designed randomised controlled trials are needed to assess the effects of routine use of maternal antibiotics for women with prelabour rupture of the membranes at or near term.

Antibiotic Prophylaxis↗
PubMed2002

A demonstration of a 1:1 correspondence between chiasma frequency and recombination using a Lolium perenne/Festuca pratensis substitution.

A single chromosome of the grass species Festuca pratensis has been introgressed into Lolium perenne to produce a diploid monosomic substitution line 2n = 2x = 14. The chromatin of F. pratensis and L. perenne can be distinguished by genomic in situ hybridization (GISH), and it is therefore possible to visualize the substituted F. pratensis chromosome in the L. perenne background and to study chiasma formation in a single marked bivalent. Recombination occurs freely in the F. pratensis/L. perenne bivalent, and chiasma frequency counts give a predicted map length for this bivalent of 76 cM. The substituted F. pratensis chromosome was also mapped with 104 EcoRI/Tru91 and HindIII/Tru91 amplified fragment length polymorphisms (AFLPs), generating a marker map of 81 cM. This map length is almost identical to the map length of 76 cM predicted from the chiasma frequency data. The work demonstrates a 1:1 correspondence between chiasma frequency and recombination and, in addition, the absence of chromatid interference across the Festuca and Lolium centromeres.

Chromosome Mapping↗
PubMed2002

Physical and genetic mapping in the grasses Lolium perenne and Festuca pratensis.

A single chromosome of the grass species Festuca pratensis has been introgressed into Lolium perenne to produce a diploid monosomic substitution line 2n = 2x = 14. In this line recombination occurs throughout the length of the F. pratensis/L. perenne bivalent. The F. pratensis chromosome and recombinants between it and its L. perenne homeologue can be visualized using genomic in situ hybridization (GISH). GISH junctions represent the physical locations of sites of recombination, enabling a range of recombinant chromosomes to be used for physical mapping of the introgressed F. pratensis chromosome. The physical map, in conjunction with a genetic map composed of 104 F. pratensis-specific amplified fragment length polymorphisms (AFLPs), demonstrated: (1) the first large-scale analysis of the physical distribution of AFLPs; (2) variation in the relationship between genetic and physical distance from one part of the F. pratensis chromosome to another (e.g., variation was observed between and within chromosome arms); (3) that nucleolar organizer regions (NORs) and centromeres greatly reduce recombination; (4) that coding sequences are present close to the centromere and NORs in areas of low recombination in plant species with large genomes; and (5) apparent complete synteny between the F. pratensis chromosome and rice chromosome 1.

Chromosomes, Plant↗
PubMed2002

Clinical ethics in rehabilitation medicine: core objectives and algorithm for resident education.

Described as the balance of values on either side of a moral dilemma, ethics and ethical issues are of increasing importance in the changing practice of rehabilitation medicine. Because the substance of ethics and true ethical issues can be difficult to identify, the education of rehabilitation residents in ethics can similarly be challenging. This article discusses topics pertinent to an understanding of clinical ethics in rehabilitation medicine and provides a method of teaching residents through an algorithm of ethical issues, learning objectives, and illustrative cases.

Algorithms↗
PubMed2001

BETAWRAP: successful prediction of parallel beta -helices from primary sequence reveals an association with many microbial pathogens.

The amino acid sequence rules that specify beta-sheet structure in proteins remain obscure. A subclass of beta-sheet proteins, parallel beta-helices, represent a processive folding of the chain into an elongated topologically simpler fold than globular beta-sheets. In this paper, we present a computational approach that predicts the right-handed parallel beta-helix supersecondary structural motif in primary amino acid sequences by using beta-strand interactions learned from non-beta-helix structures. A program called BETAWRAP (http://theory.lcs.mit.edu/betawrap) implements this method and recognizes each of the seven known parallel beta-helix families, when trained on the known parallel beta-helices from outside that family. BETAWRAP identifies 2,448 sequences among 595,890 screened from the National Center for Biotechnology Information (NCBI; http://www.ncbi.nlm.nih.gov/) nonredundant protein database as likely parallel beta-helices. It identifies surprisingly many bacterial and fungal protein sequences that play a role in human infectious disease; these include toxins, virulence factors, adhesins, and surface proteins of Chlamydia, Helicobacteria, Bordetella, Leishmania, Borrelia, Rickettsia, Neisseria, and Bacillus anthracis. Also unexpected was the rarity of the parallel beta-helix fold and its predicted sequences among higher eukaryotes. The computational method introduced here can be called a three-dimensional dynamic profile method because it generates interstrand pairwise correlations from a processive sequence wrap. Such methods may be applicable to recognizing other beta structures for which strand topology and profiles of residue accessibility are well conserved.

Bacteria↗
PubMed2001

Enhanced crystallization of the Cys18 to Ser mutant of bovine gammaB crystallin.

The cysteine residues of the gamma crystallins, a family of ocular lens proteins, are involved in the aggregation and phase separation of these proteins. Both these phenomena are implicated in cataract formation. We have used bovine gammaB crystallin as a model system to study the role of the individual cysteine residues in the aggregation and phase separation of the gamma crystallins. Here, we compare the thermodynamic and kinetic behavior of the recombinant wild-type protein (WT) and the Cys18 to Ser (C18S) mutant. We find that the solubilities of the two proteins are similar. The kinetics of crystallization, however, are different. The WT crystallizes slowly enough for the metastable liquid-liquid coexistence to be easily observed. C18S, on the other hand, crystallizes rapidly; the metastable coexisting liquid phases of the pure mutant do not form. Nevertheless, the coexistence curve of C18S can be determined provided that crystallization is kinetically suppressed. In this way we found that the coexistence curve coincides with that of the WT. Despite the difference in the kinetics of crystallization, the two proteins were found to have the same crystal forms and almost identical X-ray structures. Our results demonstrate that even conservative point mutations can bring about dramatic changes in the kinetics of crystallization. The implications of our findings for cataract formation and protein crystallization are discussed.

Amino Acid Substitution↗
PubMed2001

How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis.

BACKGROUND: Numerous small clinical trials have been carried out to study the behaviourally defined efficacy and safety of short-acting methylphenidate compared with placebo for attention-deficit disorder (ADD) in individuals aged 18 years and less. However, no meta-analyses that carefully examined these questions have been done. We reviewed the behavioural evidence from all the randomized controlled trials that compared methylphenidate and placebo, and completed a meta-analysis. METHODS: We searched several electronic sources for articles published between 1981 and 1999: MEDLINE, EMBASE, PsychINFO, ERIC, CINAHL, HEALTHSTAR, Biological Abstracts, Current Contents and Dissertation Abstracts. The Cochrane Library Trials Registry and Current Controlled Trials were also consulted. A study was considered eligible for inclusion if it entailed the following: a placebo-controlled randomized trial that involved short-acting methylphenidate and participants aged 18 years or less at the start of the trial who had received any primary diagnosis of ADD that was made in a systematic and reproducible way. RESULTS: We included 62 randomized trials that involved a total of 2897 participants with a primary diagnosis of ADD (e.g., with or without hyperactivity). The median age of trial participants was 8.7 years, and the median "percent male" composition of trials was 88.1%. Most studies used a crossover design. Using the scores from 2 separate indices, this collection of trials exhibited low quality. Interventions lasted, on average, 3 weeks, with no trial lasting longer than 28 weeks. Each primary outcome (hyperactivity index) demonstrated a significant effect of methylphenidate (effect size reported by teacher 0.78, 95% confidence interval [CI] 0.64-0.91; effect size reported by parent 0.54, 95% CI 0.40-0.67). However, these apparent beneficial effects are tempered by a strong indication of publication bias and the lack of robustness of the findings, especially those involving core ADD features. Methylphenidate also has an adverse event profile that requires consideration. For example, clinicians only need to treat 4 children to identify an episode of decreased appetite. INTERPRETATION: Short-acting methylphenidate has a statistically significant clinical effect in the short-term treatment of individuals with a diagnosis of ADD aged 18 years and less. However, the extension of this placebo-controlled effect beyond 4 weeks of treatment has not been demonstrated. Exact knowledge of the extent and definition of the short-term behavioural usefulness of methylphenidate is questioned.

Adolescent↗
PubMed2001

Families of restriction enzymes: an analysis prompted by molecular and genetic data for type ID restriction and modification systems.

Current genetic and molecular evidence places all the known type I restriction and modification systems of Escherichia coli and Salmonella enterica into one of four discrete families: type IA, IB, IC or ID. StySBLI is the founder member of the ID family. Similarities of coding sequences have identified restriction systems in E.coli and Klebsiella pneumoniae as probable members of the type ID family. We present complementation tests that confirm the allocation of EcoR9I and KpnAI to the ID family. An alignment of the amino acid sequences of the HsdS subunits of StySBLI and EcoR9I identify two variable regions, each predicted to be a target recognition domain (TRD). Consistent with two TRDs, StySBLI was shown to recognise a bipartite target sequence, but one in which the adenine residues that are the substrates for methylation are separated by only 6 bp. Implications of family relationships are discussed and evidence is presented that extends the family affiliations identified in enteric bacteria to a wide range of other genera.

Amino Acid Sequence↗
PubMed2001

Aprotinin, blood loss, and renal dysfunction in deep hypothermic circulatory arrest.

BACKGROUND: The technique of deep hypothermic circulatory arrest (DHCA) for cardiothoracic surgery is associated with increased risk for perioperative blood loss and renal dysfunction. Although aprotinin, a serine protease inhibitor, reduces blood loss in patients undergoing cardiopulmonary bypass, its use has been limited in the setting of DHCA because of concerns regarding aprotinin-induced renal dysfunction. Therefore, we assessed the affect of aprotinin on both blood transfusion requirements and renal function in patients undergoing cardiovascular surgery and DHCA. METHODS AND RESULTS: We reviewed the records of 853 patients who underwent aortic or thoracoabdominal surgery at Stanford University Medical Center between January 1992 and March 2000. Two hundred three of these patients were treated with DHCA, and 90% (183) survived for more than 24 hours. Preoperative patient characteristics and intraoperative and postoperative clinical and surgical variables were recorded, and creatinine clearance (CRCl) was calculated for the preoperative and postoperative periods; renal dysfunction was prospectively defined as a 25% reduction in CRCl. The association between perioperative variables, including aprotinin use, and renal dysfunction was assessed by ANOVA techniques. Total urine output was 1294+/-1024 mL and 3492+/-1613 mL during and after surgery, respectively. CRCl decreased significantly after DHCA from 86+/-8 mL/min (before surgery) to 67+/-4 mL/min (in the intensive care unit) (P<0.01). Thirty-eight percent of patients (70 of 183) had postoperative renal dysfunction. Multivariate regression analyses identified 5 factors independently associated with a >25% reduction in CRCl: requirement for >/=5 U of packed red blood cells(P=0.0002; OR=2.1), </=800 mL of urine collected in the operating room (P=0.0011; OR=1.9), nonuse of dopamine (P=0.0430; OR=1.6), hematocrit </=21 mg% (P=0.0343; OR=1.5), and </=2100 mL of urine during the first 24 hours in the intensive care unit (P=0.0039; OR=2.0). Aprotinin did not increase the likelihood of postoperative renal dysfunction (P=0.951), nor did it significantly reduce packed red blood cell transfusion requirements in either primary (n=107) (P=0.456) or reoperative cardiovascular (n=76) (P=0.176) procedures. During the operative period, the aprotinin group received a greater number of units of platelets (10.0 versus 6.6 U, P<0.012), fresh frozen plasma (4.8 versus 3.1 U, P<0.03), and cryoprecipitate (9.9 versus 5.4 U, P<0.002) than patients not prescribed aprotinin. Similarly, patients given aprotinin received more cryoprecipitate in the intensive care unit (7.3 versus 3.0 U, P<0.024). CONCLUSIONS: These data suggest that the administration of aprotinin to patients treated with DHCA does not increase the risk of renal dysfunction. However, aprotinin may not ameliorate the problem of perioperative blood loss in DHCA. Patients with greater requirements for packed red blood cell transfusions or reduced urine production are more likely to have postoperative renal dysfunction. Dopamine may provide renal protection in the setting of DHCA.

Aprotinin↗
PubMed2001

Menstrual cycle effects on postural stability but not optokinetic function.

We investigated the effects of the menstrual cycle on visual-vestibular interaction by measuring optokinetic function and postural stability at different phases of the cycle. Menstrual cycle phase had no significant effect on gaze-holding, optokinetic nystagmus slow phase velocity, amplitude or frequency, circularvection latency or optokinetic afternystagmus frequency, amplitude or duration. While menstrual cycle phase had no significant effect on anterior-posterior sway, it did significantly affect lateral sway (P<0.001), with sway on day 5 significantly greater than on days 12 and 21 (P<0.05 and 0.01, respectively), and sway on day 25 significantly greater than that on day 21 (P<0.05).

Adolescent↗
PubMed2001

Consent: the patients' view--a summary of findings from a study of patients' perceptions of their consent to dental care.

AIM: A study was carried out which aimed to investigate peoples' perceptions of how their consent was given for dental treatment. METHOD: A structured questionnaire was completed by 50 patients receiving treatment in the British NHS and 12 of them completed an in-depth recorded interview. The data was analysed using a combination of quantitative and qualitative methods. RESULTS: The findings showed that 80% of patients had not been given any written treatment plan (FP17DC). 79% of patients mistakenly thought that the form signed requesting NHS treatment (FP17) was a consent form. When options were offered patients were more likely to consider that they were involved in the consenting process. However consent is still often implied rather than explicit. There was a range of experience reported by patients from those who felt that the dentist made the treatment decisions to those who felt that decisions had been made collaboratively. Although some patients were happy with the way their consent was obtained examples were also given of lack of information, confusion and even of deceit. CONCLUSIONS: There is an urgent need to clarify the status of NHS documentation regarding consent and a general need for awareness to be raised in the dental profession about the importance of obtaining consent which is freely given based on appropriate information which has been adequately understood.

Dental Care↗
PubMed2001

Optokinetic reflex dysfunction in multiple sclerosis.

The aim of this study was to further investigate optokinetic reflex function in multiple sclerosis. Gaze-holding in darkness, optokinetic nystagmus, optokinetic afternystagmus and latency to circularvection were measured using electro-oculography and a rotating optokinetic drum. Gaze-holding was not significantly different between the multiple sclerosis and control groups; however, four of 23 multiple sclerosis patients exhibited eccentric gaze-evoked nystagmus. There were no significant differences in either optokinetic nystagmus frequency or latency to circularvection. However, optokinetic nystagmus slow phase velocity during rise time and amplitude during beat time were significantly reduced in the multiple sclerosis group (p < 0.05 and p < 0.0001, respectively). The time constant of optokinetic afternystagmus was also significantly reduced in the multiple sclerosis group (p < 0.005). These results indicate that optokinetic nystagmus and optokinetic afternystagmus are significantly impaired multiple sclerosis.

Adult↗
PubMed2001

Crystal cataracts: human genetic cataract caused by protein crystallization.

Several human genetic cataracts have been linked recently to point mutations in the gammaD crystallin gene. Here we provide a molecular basis for lens opacity in two genetic cataracts and suggest that the opacity occurs because of the spontaneous crystallization of the mutant proteins. Such crystallization of endogenous proteins leading to pathology is an unusual event. Measurements of the solubility curves of crystals of the Arg-58 to His and Arg-36 to Ser mutants of gammaD crystallin show that the mutations dramatically lower the solubility of the protein. Furthermore, the crystal nucleation rate of the mutants is enhanced considerably relative to that of the wild-type protein. It should be noted that, although there is a marked difference in phase behavior, there is no significant difference in protein conformation among the three proteins.

Cataract↗
PubMed2001

A newly synthesized, ribosome-bound polypeptide chain adopts conformations dissimilar from early in vitro refolding intermediates.

Little is known about the conformations of newly synthesized polypeptide chains as they emerge from the large ribosomal subunit, or how these conformations compare with those populated immediately after dilution of polypeptide chains out of denaturant in vitro. Both in vivo and in vitro, partially folded intermediates of the tailspike protein from Salmonella typhimurium phage P22 can be trapped in the cold. A subset of monoclonal antibodies raised against tailspike recognize partially folded intermediates, whereas other antibodies recognize only later intermediates and/or the native state. We have used a pair of monoclonal antibodies to probe the conformational features of full-length, newly synthesized tailspike chains recovered on ribosomes from phage-infected cells. The antibody that recognizes early intermediates in vitro also recognizes the ribosome-bound intermediates. Surprisingly, the antibody that did not recognize early in vitro intermediates did recognize ribosome-bound tailspike chains translated in vivo. Thus, the newly synthesized, ribosome-bound tailspike chains display structured epitopes not detected upon dilution of tailspike chains from denaturant. As opposed to the random ensemble first populated when polypeptide chains are diluted out of denaturant, folding in vivo from the ribosome may begin with polypeptide conformations already directed toward the productive folding and assembly pathway.

Antibodies, Monoclonal↗
PubMed2001

Distinct cysteine sulfhydryl environments detected by analysis of Raman S-hh markers of Cys-->Ser mutant proteins.

Very little is known about the character or functional relevance of hydrogen-bonded cysteine sulfhydryl (S-H) groups in proteins. The Raman S-H band is a unique and sensitive probe of the local S-H environment. Here, we report the use of Raman spectroscopy combined with site-specific mutagenesis to document the existence of five distinguishable hydrogen-bonded states of buried cysteine sulfhydryl groups in a native protein. The 666 residue subunit of the Salmonella typhimurium bacteriophage P22 tailspike contains eight cysteine residues distributed through the elongated structure. The tailspike cysteine residues display an unusual Raman S-H band complex (2500-2600 cm(-1) interval) indicative of diverse S-H hydrogen-bonding interactions in the native trimeric structure. To resolve specific Cys contributions to the complex Raman band we characterized a set of tailspike proteins with each cysteine replaced by a serine. The mutant proteins, once folded, were structurally and functionally indistinguishable from wild-type tailspikes, except for their Raman S-H signatures. Comparison of the Raman spectra of the mutant and wild-type proteins reveals the following hydrogen-bond classes for cysteine sulfhydryl groups. (i) Cys613 forms the strongest S-H...X bond of the tailspike, stronger than any heretofore observed for a protein. (ii) Cys267, Cys287 and Cys458 form robust S-H...X bonds. (iii) Moderate S-H...X bonding occurs for Cys169 and Cys635. (iv) Cys290 and Cys496 form weak hydrogen bonds. (v) It is remarkable that Cys287 contributes two Raman S-H markers, indicating the population of two distinct hydrogen-bonding states. The sum of the S-H Raman signatures of all eight mutants accurately reproduces the composite Raman band of the wild-type tailspike. The diverse cysteine states may be an outcome of the folding and assembly pathway of the tailspike, which though lacking disulfide bonds in the native state, utilizes transient disulfide bonds in the maturation pathway. This Raman study represents the first detailed assessment of local S-H hydrogen bonding in a native protein and provides information not obtainable directly by other structural probes. The method employed here should be applicable to a wide range of cysteine-containing proteins.

Amino Acid Substitution↗
PubMed2001

Experimental annotation of the human genome using microarray technology.

The most important product of the sequencing of a genome is a complete, accurate catalogue of genes and their products, primarily messenger RNA transcripts and their cognate proteins. Such a catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a genome scale. Using 'exon' and 'tiling' arrays fabricated by ink-jet oligonucleotide synthesis, we devised an experimental approach to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons. These methods can provide more accurate gene numbers and allow the detection of mRNA splice variants and identification of the tissue- and disease-specific conditions under which genes are expressed. We apply our technique to chromosome 22q under 69 experimental condition pairs, and to the entire human genome under two experimental conditions. We discuss implications for more comprehensive, consistent and reliable genome annotation, more efficient, full-length complementary DNA cloning strategies and application to complex diseases.

Algorithms↗