Whose death is it, anyway?
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Biomedical subjects
Publications and source records attributed to P Rousseau.
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In bacteria lysogenic for bacteriophage Mu, the phage repressor binds to a tripartite operator region, O1,O2,O3, to repress the lytic promoter pE, located in O2, and negatively autoregulate its own synthesis at the pCM promoter located in O3. We isolated and characterized operator mutations which lead to derepression of pE. Their location in the first and third repressor-consensus-binding sequences in O2 confirms the importance of these sites for repressor/operator interactions.
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PURPOSE: To determine the analgesic efficacy and safety of interpleural block for percutaneous biliary drainage. MATERIALS AND METHODS: In this double-blind study, 34 age- and sex-matched patients who were to undergo percutaneous biliary drainage because of malignant biliary obstruction were randomly assigned to the true-block group (30 mL 0.5% bupivacaine block) or placebo-block group; all had access to a patient-controlled analgesia (fentanyl) pump. Self medication, pain reports, blood pressure, heart rate, and oxygen saturation were monitored during and until 8 hours after drainage. The McGill Pain Questionnaire was administered 1 hour after biliary drainage. RESULTS: Patients in the placebo group self administered statistically significantly more fentanyl than did patients in the true-block group (P = .008). Peak pain scores (10-point scale) and McGill Pain Questionnaire scores were statistically significantly higher for the placebo group patients (P = .017 and P = .001, respectively). There were no differences between groups in terms of blood pressure, heart rate, and oxygen saturation. Two patients had pneumothorax caused by the interpleural block. CONCLUSION: Interpleural block was effective in decreasing pain and opioid requirements during and after percutaneous biliary drainage and did not compromise the cardiopulmonary status of the patient. However, the rate of pneumothorax was higher than previously reported.
BACKGROUND: alpha-Amylases catalyze the hydrolysis of glycosidic linkages in starch and other related polysaccharides. The alpha-amylase inhibitor (alpha-Al) from the bean Phaseolus vulgaris belongs to a family of plant defence proteins and is a potent inhibitor of mammalian alpha-amylases. The structure of pig pancreatic alpha-amylase (PPA) in complex with both a carbohydrate inhibitor (acarbose) and a proteinaceous inhibitor (Tendamistat) is known, but the catalytic mechanism is poorly understood. RESULTS: The crystal structure of pig pancreatic alpha-amylase complexed with alpha-Al was refined to 1.85 A resolution. It reveals that in complex with PPA, the inhibitor has the typical dimer structure common to legume lectins. Two hairpin loops extending out from the jellyroll fold of a monomer interact directly with the active site region of the enzyme molecule, with the inhibitor molecule filling the whole substrate-docking region of the PPA. The inhibitor makes substrate-mimetic interactions with binding subsites of the enzyme and targets catalytic residues in the active site. Binding of inhibitor induces structural changes at the active site of the enzyme. CONCLUSIONS: The present analysis reveals that there are extensive interactions between the inhibitor and residues that are highly conserved in the active site of alpha-amylases; alpha-Al1 inactivates PPA through elaborate blockage of substrate-binding sites. It provides a basis to design peptide analogue inhibitors. alpha-Amylase inhibition is of interest from several points of view, for example the treatment of diabetes and for crop protection.
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Pig pancreatic alpha-amylase (PPA, E.C. 3.2. 1. 17, 496 amino-acid residues) has been crystallized as a complex with a lectin-like inhibitor from bean Phaseolus vulgaris (224 amino-acid residues for the inhibitor monomer). The hanging-drop vapour-diffusion method was used to grow crystals from solutions containing 2-methyl-2,4-pentanediol as precipitant. The crystals belong to monoclinic space group C2 with a = 152.5, b = 80.3, c = 68.8 A, beta = 91.4 and diffract to 2.9 A resolution. A molecular-replacement solution of the structure has been obtained using the refined PPA and LoLl (Lathyrus ochrus isolectin I) atomic coordinates as starting models. Low-resolution refinement of the model is underway. The analysis reveals that the functional inhibitor molecule is dimeric and interacts with two molecules of enzyme.
The repressor of bacteriophage Mu, c, binds to three operator sites, O1, O2, and O3, overlapping two divergent promoters, which regulate the lytic and lysogenic pathways. Its binding to this operator region generates several complexes, which were analyzed by DNase I protection experiments. We demonstrate that c first binds to two 11-base pair partially repeated sequences in O2 that could represent "core" binding sites for the repressor. This initial interaction serves as an organizer of a more complex nucleoprotein structure in which O2, O1, and O3 become successively occupied. The quaternary structure of the repressor was also investigated. Size exclusion chromatography and protein-protein crosslinking experiments with chemicals that possess linking arms of various lengths indicate that the repressor oligomerizes in solution. A model is proposed describing the successive interactions of c with the operator sites O2, O1, and O3 leading to the elaboration of a higher order structure in which the early lytic functions are repressed.
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The relationship between disabled elderly veteran care receivers' functional status and their in-home family caregivers' strain was examined in this study. The convenience sample was composed of 93 dyads. Data were obtained from care receivers' health care records and included the Folstein Mini-Mental State Examination (MMS), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (ADL), and Robinson's Caregiver Strain Index (CSI). Major findings were: 52% of caregivers experienced significant strain; 59% of care receivers were cognitively impaired to some extent and were severely impaired in IADL and ADL; and the relationships between care receivers' functional status (cognitive, ADL and IADL) and caregiver strain were statistically significant.
The treatment of nonpain symptoms is integral to good palliative care of the terminally ill elder. This article reviews the management of common physical symptoms observed during the dying process, including nausea and vomiting, dyspnea, cough, constipation, diarrhea, bowel obstruction, and xerostomia. Alleviation of these symptoms is necessary for a comfortable and tranquil death for the patient, and an uncomplicated bereavement for surviving family members.
Painful bone metastases are a clear indication for the use of radiotherapy, with reported response rates of up to 85% of patients treated. In an attempt to define the optimal use of palliative radiotherapy when used in this situation, the data for the efficacy, toxicity and choice of dose and fractionation are reviewed. Although there have been some recent trials demonstrating the value of hypofractionated radiation therapy, half-body irradiation and 89-strontium, in general there is a lack of information in this clinical area, particularly on the duration of beneficial effect and on treatment toxicity. The available data suggest that single-fraction radiation is as effective as short-course fractionated treatment, and may be isotoxic when 5HT3 antagonists are used. Future implications for research are discussed.
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Integration host factor (IHF) binds in a sequence-specific manner to the bacteriophage Mu early operator. It participates with bound Mu repressor, c, in building stable, large molecular mass nucleoprotein complexes in vitro and enhances repression of early transcription in vivo. We demonstrate that, when the specific IHF binding site with the operator is mutated, the appearance of large molecular mass complexes still depends on IHF and c, but the efficiency of their formation is reduced. Moreover, the IHF-like HU protein, which binds DNA in a non-sequence-specific way, can substitute for IHF and participate in complex formation. Since the complexes require both c and a host factor (IHF or HU), the results imply that these proteins stabilise each other within the nucleoprotein structures. These results suggest that IHF and HU are directed to the repressor-operator complexes, even in the absence of detectable sequence-specific binding. This could be a consequence of their preferential recognition of DNA containing a distortion such as that introduced by repressor binding to the operator. The histone-like proteins could then stabilise the nucleoprotein complexes simply by their capacity to maintain a bend in DNA rather than by specific protein-protein interactions with c. This model is supported by the observation that the unrelated eukaryotic HMG-1 protein, which exhibits a similar marked preference for structurally deformed DNA, is also able to participate in the formation of higher-order complexes with c and the operator DNA.
The emergence of AIDS and the aging of the population, with the numerous malignant and debilitating maladies associated with growing older, have focused attention on the provision of cost-effective quality care by hospice and palliative care programs. Hospice and palliative care is a venerated system of care, which uses an interdisciplinary approach to address the medical, psychosocial, and spiritual issues that arise in the treatment of terminally ill patients. This interdisciplinary stratagem for symptom control is necessary to ensure that dying patients and their families are afforded dignity and quality of life through death and the period of familial bereavement. Although death is dominant in palliative situations, terminal care requires an affirmation of life and a recognition that dying is not an aberration of medical care but a natural and normal process. Palliative care, however, also requires a personal acceptance of death and an acknowledgment that dying does not denote a failure to provide good medical care but, rather, calls for an acquiescence that curative treatment is no longer feasible. Accordingly, the terminal state is an integral process and a time to reconcile differences so that patient and family may accept death with a minimum of physical, spiritual, and psychosocial anguish. This article discusses the various precepts cardinal to hospice and palliative care, including the philosophy of terminal care, the management of pain, the adverse effects of analgesic medications, the management of nonpain symptoms, the use of terminal sedation, and the stages of familial bereavement.
Hiccups result from a variety of causes and serve no known physiologic function. Although most episodes are time-limited, hiccups may become protracted, with serious consequences. Assessment of hiccups entails a focused history and physical examination coupled with selected laboratory tests. If a correctable malady is discovered, treatment should address the underlying disorder. However, if the cause remains unknown, therapeutic options include nonpharmacologic and pharmacologic measures. Since hiccups are common, this review provides a practical approach to the management of this bothersome symptom.