Acute asthma precipitated by accidental inhalation of sodium bicarbonate granules (Carbex)
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Acute Disease↗
Biomedical subjects
J Griffith
Publications and source records attributed to J Griffith.
ODS_BOOTSTRAP: assessing the statistical reliability of physical maps by bootstrap resampling.
In the program ODS_BOOTSTRAP we provide a methodology for quickly ordering clones in a genomic library into a physical map and for applying a statistical tool known as the bootstrap to assess the statistical reliability of a clonal ordering. Each clone is assigned a binary fingerprint by one of a variety of experimental approaches to physical mapping. For example, the binary fingerprints might be generated by hybridizing a panel of m probes to a library of n clones. The resulting n x m binary data matrix, X, is input to ODS_BOOTSTRAP, which utilizes the similarity in binary fingerprints of clones to construct a physical map. Under this particular implementation of bootstrap resampling, the m probes (or columns of the data matrix) are sampled randomly with replacement in the computer to generate a new n x m data matrix, X*, from which a second physical map is constructed. The resampling process is repeated 100 or more times to generate 100 or more X* matrices. The resulting 100 or more physical maps are compared with the original physical map based on the original data matrix X by counting how often links in the original physical map reappear. Three confidence statistics are introduced for each link in a physical map. The statistic C1 is defined as the percentage of time two neighboring clones on the original map reappear as neighbors under resampling. The statistic C2 is defined as the percentage of time that two neighboring clones i and j on the original map reappear as neighbors or that a clone with an identical binary fingerprint to clone i reappears as a neighbor to clone j. The statistic C3 is defined as the percentage of time that two neighboring clones on the original map reappear in the same contig under resampling.
Algorithms↗
Closing the audit loop: a patient satisfaction survey.
A patient satisfaction survey was carried out in a nuclear medicine department of a large acute hospital. Surveys were initially carried out by interview and postal techniques, with approximately 100 responders in each category. The responses to each question were not significantly different for the two types of survey, although overall there was a significantly larger number of dissatisfied responses in the postal survey (22%) compared with the interview study (12%). The postal survey was repeated after 1 year, thus completing the audit loop. A significant reduction in dissatisfied responses has occurred in those areas which had been addressed following the criticisms revealed by the first survey.
Hospital-Patient Relations↗
Core values in health care reform: a communitarian approach.
Controlling health care costs should allow the nation to provide more health services and higher quality care to more people. The authors are concerned, however, that many of the reform efforts will unwittingly undermine the culture of care in their pursuit of savings and access. This article is a plea to maintain the core moral values and the social and institutional commitments that are essential in the delivery of care, so that the health care community is not turned into a health industry. The authors' communitarian approach aims to preserve the balance between individual rights and social responsibilities, the moral integrity of a caring society, and the unique character of mutual trust between patients and health care personnel. They advocate an orientation toward preventing disease and promoting health, an imperative of reforming the violent, reckless, and costly aspects of American society, and a moral justification for cutting administrative waste, defensive medicine, and excessive profits rather than rationing beneficial and humane health services.
Child↗
A further analysis of the use of cytomegalovirus immune globulin in orthotopic liver transplant patients at risk for primary infection. Boston Center for Liver Transplantation CMVIG-Study Group.
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Acyclovir↗
Cytomegalovirus immune globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial.
OBJECTIVE: To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants. DESIGN: Randomized, multicenter, placebo-controlled, double-blind trial. SETTING: Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). PATIENTS: One hundred forty-one liver transplant recipients completed the study. INTERVENTION: CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16. MEASUREMENTS: Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness. RESULTS: Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group). CONCLUSION: CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.
Acyclovir↗
Replicatively active complexes of DnaA protein and the Escherichia coli chromosomal origin observed in the electron microscope.
DnaA protein and the Escherichia coli chromosomal origin (oriC) form an initial complex at an early stage in the initiation of DNA replication. We have used electron microscopy to determine which structure among the several formed in the reconstitution of this multicomponent system is the replicatively active complex. One distinctive structure could be correlated with activity and localized to oriC, whilst several others could not. Formation of an open complex in the next stage of initiation was accompanied by the presence of a structure similar in size and shape to that of the functional initial complex. Whereas the initial complex was observed with either ATP or the ADP-forms of DnaA protein, only the ATP-form was effective in producing the open complex. Mutagenesis of several DNA sequence elements in oriC, known to be important for replication, was employed to determine the effects of these alterations on formation of the initial complex. As judged by electron microscopy and by functional assays, the region containing the four 9-mer dnaA boxes proved to be essential for the formation of the initial complex, while the three contiguous AT-rich 13-mers, known sites for opening of oriC, were not.
Adenosine Diphosphate↗
RecA binding to bulge- and mismatch-containing DNAs. Certain single base mismatches provide strong signals for RecA binding equal to multiple base bulges.
Studies from several laboratories have demonstrated that RecA protein can recognize a variety of perturbations in the DNA helix. Here, using a nitrocellulose filter binding assay, it was observed that RecA bound to bulge-containing DNAs more effectively than non-bulged DNA. The degree of binding of RecA protein to bulged DNA was dependent on the conformation of the bulged bases and the kinking angles produced by the bulges as determined by the type and number of bases in the bulge. Although a single base mismatch does not kink DNA, RecA protein showed preferential binding to DNAs containing certain single base mismatches. An A.C mismatch flanked by A.T base pairs in a 28-base pair (bp) DNA facilitated the binding of RecA protein to the same high level as when the 28-bp DNA contained a 4-base cytosine bulge. Chemical probing techniques were used to examine the structure of DNA within the RecA filament. It was found that upon binding of RecA protein, the DNA helix becomes accessible over at least 14 bp, and the degree of sensitivity agrees with the binding efficiency of RecA protein.
Base Composition↗
Bidirectional excision in methyl-directed mismatch repair.
Using electron microscopy and indirect end-labeling methods, we have examined excision tracts produced by the Escherichia coli methyl-directed mismatch repair system on a closed circular G-T heteroduplex that contains a single d(GATC) site. Despite differing polarities of the unmodified strand in the two hemimethylated derivatives of the heteroduplex, that portion of the unmethylated strand spanning the shorter path between the d(GATC) site and mismatch is targeted for excision in both cases. Mismatch-provoked excision occurring on both hemimethylated DNAs requires DNA helicase II, but exonuclease requirements for the reaction depend on heteroduplex orientation. When the d(GATC) sequence on the unmodified strand resides 3' to the mismatch as viewed along the shorter path, excision requires exonuclease I. Excision occurring on the alternate hemimethylated heteroduplex depends on the 5'--> 3' hydrolytic activity of exonuclease VII. Coupled with the previous demonstration that repair initiates via the mismatch-provoked, MutHLS-dependent incision of the unmethylated strand at a d(GATC) sequence (Au, K.G., Welsh, K., and Modrich, P. (1992) J. Biol. Chem. 267, 12142-12148), these findings indicate an excision mechanism in which helicase II displacement renders the incised strand sensitive to the appropriate single-strand exonuclease. Our data imply that hydrolysis commences at the d(GATC) site, proceeds to a point beyond the mismatch, and terminates at a number of discrete sites within a 100-nucleotide region just beyond this site. The extent of excision is therefore controlled by one or more components of the repair system.
Adenosine Triphosphatases↗
Herpes simplex virus 1 single-strand DNA-binding protein (ICP8) will promote homologous pairing and strand transfer.
The herpes simplex virus type 1 encoded ICP8 protein binds single-stranded (ss) DNA and is required for DNA replication in vitro. We have used electron microscopy to examine the ability of ICP8 to promote homologous pairing and strand transfer reactions. Visualization of M13 ssDNA-ICP8 complexes showed that they preferentially bound and enveloped homologous double-stranded (ds) DNA fragments; their deproteinization released ssDNA circles containing dsDNA segments, and an equal number of linear single strands. Optimal transfer required Mg2+ but not nucleoside triphosphates, and showed a fourfold preference for dsDNA fragments with a few bases recessed ends. Gel electrophoretic analysis confirmed the strand transfer activity of ICP8.
DNA, Circular↗
Pituitary imaging is essential for women with moderate hyperprolactinaemia.
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Adenoma↗
Radiometric assay of red cell and plasma cholinesterase in pesticide appliers from Minnesota.
In this study we demonstrate the uses of radiometric assay to detect anticholinesterases in a human population (N = 80) exposed to a broad spectrum of pesticides. The assay is nondilutional. Therefore, anticholinesterase (AChE) agents with low binding affinity can be detected. Our initial results show statistically significant exposure-related decreases in either red cell (AChE) or plasma cholinesterase activity ((butyrl)cholinesterase; BuChE) occurred not only among pesticide appliers who use organophosphates, but also among appliers of the fumigant phosphine. These data extend earlier observations made in laboratory animals exposed to this fumigant. Significant exposure-related decreases in AChE activity were seen in herbicide appliers and appear to be associated with exposure to the herbicide 2-methoxy-3,6-dichlorobenzoic acid. There was no evidence of exposure-related decreases in BuChE activity in herbicide appliers. Our in vivo data, coupled with preliminary in vitro studies of phosphine (50% AChE inhibition, 10 ppm) and 2-methoxy-3,6-chlorobenzoic acid (50% AChE and BuChE inhibition, 70 ppm), suggest that the radiometric assay may be used to detect a broader spectrum of biologically active anticholinesterase agents.
Acetylcholinesterase↗
Neurophysiological and neuropsychological evidence for attentional dysfunction in schizophrenia.
The behavior of the P50 wave of the auditory evoked potential in a paired stimulus or conditioning-testing paradigm has been used as a measure of sensory gating disturbance in schizophrenia. Schizophrenics fail to decrement the P50 response to the second stimulus of the pair, so that the ratio of the test to the conditioning amplitude is elevated over normal values. The aim of this study was to compare this neurophysiological measure to neuropsychological measures of attention and memory. As expected, schizophrenics performed worse than controls on most measures. The time to complete a digit cancellation test, a measure of sustained attention, was found to be particularly longer in schizophrenics than in control subjects. Furthermore, the increased time to complete this task correlated with the increased ratio of the amplitude of the test P50 response to the conditioning response in the schizophrenics. Thus, a neurophysiological defect in sensory gating may relate to a disorder in sustained attention in schizophrenia. Although the P50 wave may come from the hippocampus, neuropsychological measures of verbal learning and memory were not correlated with alterations in the P50 ratio.
Adult↗
Photoelastic evaluation of the standard bionator appliance.
A study was undertaken to demonstrate the forces in the craniofacial complex generated by the activation of the standard bionator appliance. A three-dimensional skull replica of an orthodontic patient with a Class II Division 1 malocclusion in the mixed dentition was fabricated using a urethane based photoelastic material to simulate bone. Four muscles of mastication were simulated on the photoelastic model. Various anatomical areas of the skull were viewed in a circular polariscope and recorded photographically before and after inserting the bionator. The downward and forward repositioning of the lower jaw by the bionator appliance caused various stresses on the craniofacial complex. The photoelastic stresses visualized in this investigation would most likely cause: an increase in the gonial angle; downward repositioning of the midface; and a posterior displacement and expansion of the maxilla.
Activator Appliances↗
Use of ganciclovir plus cytomegalovirus immune globulin to treat CMV pneumonia in orthotopic liver transplant recipients. The Boston Center for Liver Transplantation CMVIG-Study Group.
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Adult↗
Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics.
Diminished gating of the P50 auditory evoked response to repeated stimuli is a psychophysiological feature of schizophrenia, that is also present in many relatives of patients. Animal models of auditory sensory gating indicate that nicotinic cholinergic neurotransmission is a critical neuronal substrate. The aim of this experiment was to determine if the deficit in sensory gating could be reversed by nicotine administration. Nonsmoking relatives of schizophrenics with abnormal sensory gating were selected as subjects for this initial double-blind trial, to avoid effects of psychotropic medications that might complicate trials in schizophrenic patients themselves. Nicotine-containing gum increased P50 sensory gating to near normal levels within 30 min of administration. The effect was transient; the gating of P50 returned to baseline levels within 1 hr. There was no change observed after placebo administration. In one of the subjects, the anticholinesterase inhibitor physostigmine similarly normalized P50 gating. The results are consistent with the hypothesis that nicotinic cholinergic neurotransmission may mediate a familial psychophysiological deficit in schizophrenia.
Adult↗
Electron microscopic study of (A)BC excinuclease. DNA is sharply bent in the UvrB-DNA complex.
Nucleotide excision repair in Escherichia coli is initiated by the UvrA, UvrB and UvrC proteins. UvrA is the damage recognition subunit, makes an A2B1 complex with the targeting subunit UvrB, and the complex binds to the lesion site; UvrA dissociates leaving behind a very stable UvrB-DNA complex that is recognized by the trigger subunit, UvrC, and the ensuing UvrB-UvrC heterodimer makes two incisions, one on either side of the lesion. Using electron microscopy, we investigated the structures of these early A, A-B intermediates on DNA containing ultraviolet light photoproducts. UvrA, which is known to bind to DNA as a dimer and produce a DNase I footprint of 33 base-pairs does not change the trajectory of DNA appreciably. The A2B1 complex clearly shows a bipartite structure and its effect on the trajectory of the DNA was not consistently straight or kinked. In contrast, the DNA in the preincision UvrB-DNA complex appears to be severely kinked; 43% of the molecules are bent by 80 degrees or more, with an average bending angle of 127 degrees. It appears that protein-induced bending is an important step on the pathway leading to excision of the damaged nucleotide by (A)BC excinuclease.
Adenosine Triphosphatases↗
Visualization of diagnostic heteroduplex DNAs from cystic fibrosis deletion heterozygotes provides an estimate of the kinking of DNA by bulged bases.
Previous studies (Hsieh, C.-H., and Griffith, J. D. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 4833-4837) of DNAs containing extra or bulged bases on one of the two strands of a duplex showed that they exhibit slower electrophoretic mobility than non-bulged DNAs, indicating that bulges create stiff kinks in the DNA. Here we paired a 97-base single-stranded DNA from the intact cystic fibrosis (CF) gene with a complementary 94-base strand containing a central 3-base deletion (delta F508), common to many CF patients. This produced a 94-base pair DNA with a central 3-base bulge. Visualization of these DNAs by electron microscopy showed that twice as many bulge-containing DNAs had a central kink as compared with the non-bulged controls. Examination of the distribution of kinking angles showed that the bulged population contained 5-7-fold more molecules with a central kink of 80 +/- 10 degrees than did the control molecules. When the 3-base bulge was replaced by a 3-base gap, the resulting duplex DNA showed central kinks with a somewhat lower frequency but greater range of kinking angles.
Base Sequence↗