A chaperonin apical domain from the thermophilic bacterium Thermus Aquaticus.
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Biomedical subjects
Publications and source records attributed to D J Baker.
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Shaken Baby Syndrome is a complex disorder with implications for family members (especially the victim's mother) that are felt long after the emergency diagnosis and treatment of the child are concluded. The authors conducted a Women's Support Group for parolees over a two year period. Included in its group membership were several women who had been jailed for child abuse related crimes. This article synthesizes the significant progress in the research from the medical, legal, social, nursing, and preventive health perspectives on Shaken Baby Syndrome. A case study is used to illustrate the phenomenon of victimization of the mother, typically the nonoffending parent in Shaken Baby Syndrome. The difficulties of diagnosing Shaken Baby Syndrome in a timely manner are presented with emphasis on the diagnostic ambiguities confronting the various medical and nursing providers and nonoffending perpetrators. The case study attempts to raise the consciousness of nurses, with whom the nonoffending parents come into contact in the vast array of health service settings, as well as provide specific recommendations for enhancing community health nursing practice.
The effectiveness of video-based staff training with manager-led exercises in improving staff performance in residential support for persons with disabilities was examined. Research staff assisted two residential program managers to implement staff training in health and safety, basic support, and residential support values. Results showed improvement in (a) staff members' washing hands when appropriate, (b) wearing gloves when appropriate, and (c) frequency of positive interactions with residents. These changes in staff behavior maintained over a 6-month follow-up. Following the values training, in one house, brief increases were observed in frequency of residents' community activities. These changes did not maintain. No improvements in these measures were noted in the other house. Implications of these findings for assurance of competent staff performance with residents were discussed.
The authors discuss the creation of a police chaplain program at their hospital--why it was needed, the preparations that were necessary, the recruitment process, and the important role the police chaplain plays.
Substantial evidence indicates that triglyceride-rich lipoprotein remnants are atherogenic. Additional research has, however, been limited by available methods for separation and quantification of remnants. We have evaluated an immunoseparation assay developed to measure cholesterol in remnant-like particles (RLP-C). This method uses monoclonal antibodies to human apolipoproteins B-100 and A-I to remove most of the apolipoprotein B-100-containing lipoproteins (namely LDL and nascent VLDL) and apolipoprotein A-I-containing lipoproteins (namely chylomicrons and HDL), leaving behind a fraction of triglyceride-rich lipoproteins, including chylomicron and VLDL remnants, both of which are enriched in apolipoprotein E. Cholesterol in the unbound fraction is measured with a sensitive enzymatic assay. The RLP-C concentration was highly correlated with total triglyceride-rich lipoproteins (sum of VLDL-cholesterol and IDL-cholesterol) separated by ultracentrifugation and by polyacrylamide gel electrophoresis (r = 0.86 and 0.76, respectively). The within-run and run-to-run imprecision (CV) of the assay was approximately 6% and 10%, respectively. The assay was not affected by hemoglobin up to 5000 mg/L (500 mg/dL), bilirubin up to 342 mmol/L (20 mg/dL), glucose up to 67 mmol/L (1200 mg/dL), or ascorbic acid up to 170 mmol/L (3.0 mg/dL). In 726 subjects (men, n = 364; women, n = 362) in the US, the 75th percentiles of RLP-C concentration were 0.17 mmol/L (6.6 mg/dL) and 0.23 mmol/L (8.8 mg/dL) in sera obtained after overnight fasting or randomly, respectively. A group of 151 patients from nine US centers and one Canadian center with coronary artery atherosclerosis established by angiography had higher median RLP-C concentrations than 302 gender- and age-matched controls (P <0.05). We conclude that the RLP-C assay compares favorably to ultracentrifugation and electrophoresis and provides a convenient and economical approach to measure triglyceride-rich lipoprotein remnants in routine clinical laboratories.
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We describe evidence for a sequence of events in which the Human DNA(cytosine-5)methyl-transferase first methylates spontaneous single-stranded conformers (SSCs) and then stalls at the methylated site to produce a complex with the conformationally unusual DNA. This property of the enzyme is a result of its ability to respond to a general loss of symmetry at its CG recognition site. The data suggest that DNA methyltransferase, itself, may physically participate in biological processes that distinguish between DNA that is in the normal Watson-Crick paired conformation and DNA that is conformationally unusual (e.g. a hairpin loop or misassembled replication intermediate). The in vitro methylation of spontaneous SSCs from the Huntington's locus illustrates the phenomenon.
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A system for addressing in the construction of macromolecular assemblies can be based on the biospecificity of DNA (cytosine-5) methyltransferases and the capacity of these enzymes to form abortive covalent complexes at targeted 5-fluorocytosine residues in DNA. Using this system, macromolecular assemblies have been created using two representative methyltransferases: M-HhaI and M x MspI. When 5-fluorocytosine (F) is placed at the targeted cytosine in each recognition sequence in a synthetic oligodeoxynucleotide (GFGC for M x HhaI or FCGG for M x MspI), we show that the first recognition sequence becomes an address for M x HhaI, while the second sequence becomes an address for M x MspI. A chimeric enzyme containing a dodecapeptide antigen linked to the C terminus of M-HhaI retained its recognition specificity. That specificity served to address the linked peptide to the GFGC recognition site in DNA. With this assembly system components can be placed in a preselected order on the DNA helix. Axial spacing for adjacent addresses can be guided by the observed kinetic footprint of each methyltransferase. Axial rotation of the addressable protein can be guided by the screw axis of the DNA helix. The system has significant potential in the general construction of macromolecular assemblies. We anticipate that these assemblies will be useful in the construction of regular protein arrays for structural analysis, in the construction of protein-DNA systems as models of chromatin and the synaptonemal complex, and in the construction of macromolecular devices.
This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.
The need to consider the problem of acute toxic injury in the prehospital context emphasized by the recent use of highly toxic agents of warfare in terrorist attacks. Toxic agents differ widely in their nature but may be considered to have four distinct properties: toxicity, latency, persistency and transmissibility. Toxicity and latency determine the onset and pathophysiology of the poisoning and therefore the clinical management. Persistency and transmissibility determine the level of hazard to rescue personnel and the evacuation system and therefore the rationale of logistic management. Previously, special emphasis has been given to the importance of isolation and decontamination of the patient before any medical intervention can occur. This approach, however, although essential for the safety of medical responders may not be in the best interests of the patient who may be in a life-threatening situation within a contaminated zone (CONZONE). Toxic injury may require more rapid help than traumatic injury; moreover, traumatic and toxic injury may co-exist, as in the case of explosion with toxic emission. The special skills required are defined in the TOXALS programme and must now become a standard part of the training and practice of prehospital care medical care.
1. Neuromuscular (NM) changes resulting from organophosphate exposure are known to be complex. After severe acute poisoning recovery from initial depolarisation paralysis may be followed in a limited number of cases by onset of a non-depolarisation paralysis (the Intermediate Syndrome). It is not clear whether this block arises subclinically in all cases of poisoning as a sequel to the initial depolarisation. 2. Single fibre electromyography (SFEMG) is a sensitive clinical neurophysiological technique allowing detection of subclinical changes at the neuromuscular junction. In the study reported it has been used to examine changes in NM transmission in the forearm of fit volunteers exposed to a low level of sarin (isopropyl methyl phosphonofluoridate). 3. Small changes in SFEMG were seen at three hours and three days after an exposure sufficient to cause a reduction in red cell acetyl cholinesterase to 60% of normal. The SFEMG changes were not accompanied by any clinical neuromuscular symptoms or signs and returned to normal 2 years after exposure. 4. The results indicate that there are reversible subclinical changes compatible with the development of non-depolarising NM block without frank clinical expression. In the small population examined there were individual variations in response which may reflect differences in safety margin at the neuromuscular junction.
OBJECTIVE: To collate information relating to the current use of marketed semen for therapeutic donor insemination (DI) in the United States. DATA IDENTIFICATION: Literature was identified by Medline search and government document review. LITERATURE SELECTION: Materials selected for review included empirical studies, policy reviews, legal documents, and government surveys relating to use of donor sperm. RESULTS: Use of marketed (donor) sperm is associated with significant medical, genetic, and psychological risk. These risks directly affect the individuals involved in therapeutic DI. Also, the public's health is involved because these risks include transmission of infectious disease and genetic anomalies. Legal and social concerns associated with therapeutic DI include offspring's knowledge of genetic endowment, parental responsibility, and donor confidentiality. This analysis shows that policies currently in place regarding the use of marketed semen in therapeutic DI do not ensure consumer safety and do not protect society's interest. CONCLUSIONS: Current policies need to be improved to protect those directly involved in the therapeutic DI process and to address public health and societal concerns. Recommendations include: [1] programs to assure quality and safety of marketed sperm, [2] implementation of a central registry to collect information about the use and outcomes of therapeutic DI, and [3H] expansion of available therapeutic DI guidelines to address psychological and social support for persons involved in therapeutic DI.
Myiasis, the infestation of humans or other vertebrates with fly larvae, may appear as furuncular nodules. Furuncular myiasis occurring in the Western hemisphere, especially in Central and South America, is usually caused by Dermatobia hominis infestation. Travel history, gross examination, and histologic evaluation of the submitted fly larvae will allow the clinician and dermatopathologist to identify the causative organism. We report two cases of furuncular myiasis due to Dermatobia hominis and review the clinical and histopathologic findings pertinent to its diagnosis. In addition, we attempted to identify some of the cardinal internal structures of this organism by extrapolating known information about insect internal anatomy and physiology to the structures visualized during serial transverse sectioning of the larvae.
Synthetic oligodeoxyribonucleotide duplexes have been used to study the methylation specificity of M.HpaII, a bacterial DNA methyltransferase. Substrates of four types were compared. A 30-mer containing a Watson-Crick paired CCGG recognition sequence was rapidly methylated at the central cytosine on each strand in the recognition sequence. A 30-mer containing an asymmetrically methylated recognition sequence, of the type transiently produced by DNA replication, was rapidly methylated at the central cytosine on the unmethylated strand. A heteroduplex containing an A.C mispair in the recognition sequence (CCGG/CCAG) was rapidly methylated at the cytosine in the mispair. A heteroduplex containing an A.C and an adjacent C.C mispair in the recognition sequence (CCGG/CCCA) was not methylated at a significant rate. The results show that M.HpaII can tolerate a single mispair at its recognition site in a heteroduplex without loss of activity or specificity.
Runs of G residues on the G-rich strands of 30mers from the region spanning codon 12 of c-Ha-ras appear to be protected against chemical modification by dimethylsulfate. This suggests that the G-rich strand might spontaneously form a Hoogsteen-paired quadruplex, which is characteristic of telomere-like DNA sequences. In this report we show that the predominant species in 1:1 mixtures of complementary 30mers from this region are duplex DNA and a smaller amount of unimolecular foldback formed by the C-rich strand. Foldbacks of this type resemble structures first observed in the C-rich strand of telomeric DNA and also occur at the CCG triplet repeat present in the FMR-1 gene of human fragile X syndrome. Foldbacks from the C-rich strand of c-Ha-ras and the FMR-1 triplet repeat are exceptional substrates for the human methyltransferase in isolation. Substituting inosine for guanosine alters the secondary structure of the folded oligomers and dramatically reduces their ability to serve as substrates for the human methyltransferase, suggesting that secondary structure is required for recognition by the enzyme. These findings suggest that one mechanism by which methyl groups accumulate in the c-Ha-ras region of chromosome 11 during carcinogenesis and at the FMR-1 locus during repeat expansion at fragile X may be structurally induced de novo methylation at sites undergoing local conformational change. Such methylation might serve to mark unusual structures for repair. In the absence of repair, asymmetrically methylated duplexes produced by resolution of the unusual structures would be rapidly converted to symmetrically methylated duplexes through the methyl-directed activity also carried by the human methyltransferase.
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