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Biomedical subjects

A Murphy

Publications and source records attributed to A Murphy.

At least 55 records · Page 3Linked to original sources

Laboratory-supported influenza surveillance in Victorian sentinel general practices.

Laboratory-supported influenza surveillance is important as part of pandemic preparedness, for identifying and isolating candidate vaccine strains, for supporting trials of anti-influenza drugs and for refining the influenza surveillance case definition in practice. This study describes the implementation of laboratory-supported influenza surveillance in Victorian sentinel general practices and provides an estimate of the proportion of patients with an influenza-like illness proven to have influenza. During 1998 and 1999, 25 sentinel general practices contributed clinical surveillance data and 16 metropolitan practices participated in laboratory surveillance. Serological, virus-antigen detection, virus culture and multiplex polymerase chain reaction procedures were used to establish the diagnosis of influenza. Two laboratories at major teaching hospitals in Melbourne provided additional data on influenza virus identification. General practice sentinel surveillance and laboratory identification of influenza provided similar data on the pattern of influenza in the community between May and September. The clinical suspicion of influenza was confirmed in 49 to 54 per cent of cases seen in general practice.

Adolescent↗

Avian somatotrophs: differentiation, morphology, distribution, and regulation.

Growth hormone (GH) is primarily synthesized, stored, and released by pituitary somatotrophs. These cells comprise a highly labile population that continuously undergoes proliferation, differentiation, and morphogenesis in response to changing physiological stimuli. They are also functionally and morphologically heterogeneous with distinct spatial and temporal distribution within the pituitary gland. The characteristics of these cells are discussed in this brief review.

Animals↗

Remarkable affinity and selectivity for Cs+ and uranyl (UO22+) binding to the manganese site of the apo-water oxidation complex of photosystem II.

The size and charge density requirements for metal ion binding to the high-affinity Mn2+ site of the apo-water oxidizing complex (WOC) of spinach photosystem II (PSII) were studied by comparing the relative binding affinities of alkali metal cations, divalent metals (Mg2+, Ca2+, Mn2+, Sr2+), and the oxo-cation UO22+. Cation binding to the apo-WOC-PSII protein was measured by: (1) inhibition of the rate and yield of photoactivation, the light-induced recovery of O2 evolution by assembly of the functional Mn4Ca1Clx, core from its constituent inorganic cofactors (Mn2+, Ca2+, and Cl-); and by (2) inhibition of the PSII-mediated light-induced electron transfer from Mn2+ to an electron acceptor (DCIP). Together, these methods enable discrimination between inhibition at the high- and low-affinity Mn2+ sites and the Ca2+ site of the apo-WOC-PSII. Unexpectedly strong binding of large alkali cations (Cs+ >> Rb+ > K+ > Na+ > Li+) was found to smoothly correlate with decreasing cation charge density, exhibiting one of the largest Cs+/Li+ selectivities (>/=5000) for any known chelator. Both photoactivation and electron-transfer measurements at selected Mn2+ and Ca2+ concentrations reveal that Cs+ binds to the high-affinity Mn2+ site with a slightly greater affinity (2-3-fold at pH 6.0) than Mn2+, while binding about 10(4)-fold more weakly to the Ca2+-specific site required for reassembly of functional O2 evolving centers. In contrast to Cs+, divalent cations larger than Mn2+ bind considerably more weakly to the high-affinity Mn2+ site (Mn2+ >> Ca2+ > Sr2+). Their affinities correlate with the hydrolysis constant for formation of the metal hydroxide by hydrolysis of water: Me2+aq --> [MeOH]+aq + H+aq. Along with the strong stimulation of the rate of photoactivation by alkaline pH, these metal cation trends support the interpretation that [MnOH]+ is the active species that forms upon binding of Mn2+aq to apo-WOC. Further support for this interpretation is found by the unusually strong inhibition of Mn2+ photooxidation by the linear uranyl cation (UO22+). The intrinsic binding constant for [MnOH]+ to apo-WOC was determined using a thermodynamic cycle to be K = 4.0 x 10(15) M-1 (at pH 6.0), consistent with a high-affinity, preorganized, multidentate coordination site. We propose that the selectivity for binding [MnOH]+, a linear low charge-density monocation, vs symmetrical Me2+ dications is functionally important for assembly of the WOC by enabling: (1) discrimination against higher charge density alkaline earth cations (Mg2+ and Ca2+) and smaller alkali metal cations (Na+ and K+) that are present in considerably greater abundance in vivo, and thus would suppress photoactivation; and (2) higher affinity binding of the one Ca2+ ion or the remaining three Mn2+ ions via coordination to form mu-hydroxo-bridged intermediates, apo-WOC-[Mn(mu-OH)2Mn]3+ or apo-WOC-[Mn(mu-OH)Ca]3+, during subsequent assembly steps of the native Mn4Ca1Clx core. In contrast to more acidic Me2+ divalent ion inhibitors of the high-affinity Mn2+ site, like Ca2+ and Sr2+, Cs+ does not accelerate the decay of the first light-induced intermediate, IM1, formed during photoactivation (attributed to apo-WOC-[Mn(OH)2]+). The inability of Cs+ to promote decay of IM1, despite having comparable affinity as Mn2+, is consistent with its considerably weaker Lewis acidity, resulting in the reprotonation of IM1 by water becoming the rate-limiting step for decay prior to displacement of Mn2+. All four different lines of evidence provide a self-consistent picture indicating that the initial step in assembly of the WOC involves high-affinity binding of [MnOH]+.

Alkalies↗

Genetic selection of short peptides that support protein oligomerization in vivo.

An important goal in protein engineering is to control associations between designed proteins. This is most often done by fusing known, naturally occurring oligomerization modules, such as leucine zippers [1] [2] [3], to the proteins of interest [4] [5] [6]. It is of considerable interest to design or discover new oligomerization domains that have novel binding specificities [7] [8] [9] [10] [11] in order to expand the 'toolbox' of the protein engineer and also to eliminate associations of the designed proteins with endogenous factors. We report here a simple genetic selection scheme through which to search libraries for peptides that are able to mediate homodimerization or higher-order self-oligomerization of a protein in vivo. We found several peptides that support oligomerization of the lambda repressor DNA-binding domain in Escherichia coli cells, some of them as efficiently as the endogenous dimerization domain or the GCN4 leucine zipper. Many are very small, comprising as few as six residues. This study strongly supports the notion that peptide sequence space is rich in small peptides, which might be useful in protein engineering and other applications.

Amino Acid Sequence↗

A retrospective examination of in-home educational visits to reduce childhood lead levels.

A number of human health effects from lead are well known. However, the means for reducing lead exposure in children has been a subject of uncertainty. This paper presents results of a retrospective study of educational lead reduction interventions in Milwaukee, Wisconsin for children who had elevated blood lead levels between 20 and 24 microg/dl. The study examined Milwaukee Health Department (MHD) records of baseline and follow-up blood lead measurements. A study group of children received an in-home educational visit by an MHD paraprofessional. The educational visits last about an hour and the importance of reducing lead exposure, nutritional suggestions, and dust clean-up practices and behavioral changes that can reduce lead exposure are discussed. After the intervention, the average observed blood lead level (n=187) declined by 4.2 microg/dl or by about 21%. A decline of 1.2 microg/dl (6%) was also observed in a reference group of 226 children who did not receive an MHD in-home visit. The decline in the reference group may be partially due to education at the clinics taking the blood samples. The study group had a decline in blood lead levels 3.1 microg/dl (15%) greater than the reference group, with the difference between groups being statistically significant with a P value of less than 0.001. Although significant exposures remained in most of the children studied, important lead reductions were observed with this relatively inexpensive and simple intervention. Education in the homes of families at risk for lead poisoning may be an effective component of programs to reduce blood lead levels.

Blood Specimen Collection↗

Low-cost household paint abatement to reduce children's blood lead levels.

The purpose was to examine the effectiveness of low-cost abatement on children's blood lead levels. Blood lead was analyzed before and after abatement in 37 homes of children under 7 years old with initial blood lead levels of 25-44 microgram/dL. Ninety-five percent of homes were built before 1950. Abatement methods used were wet-scraping and repainting deteriorated surfaces and wrapping window wells with aluminum or vinyl. A control group was retrospectively selected. Control children were under 7 years old, had initial blood lead levels of 25-44 microgram/dL and a follow-up level at least 28 days afterward, and did not have abatements performed in their homes between blood lead levels. After abatement, statistically significant declines occurred in the intervention children's blood lead levels. The mean decline was 22%, 1 to 6 months after treatment. After adjustment for seasonality and child's age, the mean decline was 6.0 microgram/dL, or 18%. The control children's blood levels did not decline significantly. There was a mean decline of 0.25 microgram/dL, or 0.39%. After adjustment for seasonality and age, the mean decline for control children was 1.6 microgram/dL, or 1.8%. Low-cost abatement and education are effective short-term interim controls.

Child↗

Evaluation of a computerized contraceptive decision aid for adolescent patients.

Recent efforts to involve patients more actively in therapeutic decisions have suggested the relevance of computer-based interventions at clinic visits. This paper presents a longitudinal, experimental study evaluating a computer-based contraceptive decision aid in Chicago and Madison family planning clinic visits. Patient interviews at three time points evaluated patient acceptance by and program impact on 949 young women. Both Chicago and Madison patients reported high acceptance. The program resulted in improved short-term knowledge and confidence in oral contraceptive (OC) efficacy for Chicago and Madison patients. In addition, compared to their control group, Madison experimental group patients had higher OC knowledge 1 year after the initial visit and a trend for fewer pregnancies (P < 0.074). Compared to their control group, a higher percent of the Chicago experimental group patients adopted OC's after stating their intention to do so at the initial visit. Exposure to the computer program had no observable impact on the number of months on the oral contraceptive for Chicago or Madison patients. Overall findings suggest the usefulness of informatics tools as a supplement to patient-provider interactions.

Adolescent↗

Vital capacity reservoir and online measurement of childhood nitrosopnea are linearly related. Clinical implications.

Hypernitrosopnea, a robust marker for childhood asthma, is measured reproducibly in mixed vital capacity (VC) expirates. Recent guidelines for measurement of expired nitric oxide (NO) in adults have favored use of an online (OL), flow-dependent technique. We compared VC and OL NO measurements in 14 asthmatic and 11 control children 5 through 18 yr of age. After spirometry, subjects breathed both into an open-ended reservoir (20 cm H2O resistance) and into a tedlar bag (VC maneuver). End-expiratory pressure > 5 cm H2O was continuously maintained during VC measurements, and the velum remained shut. Eight additional children (24% of total number of subjects) were unable reproducibly to perform the OL measurement at constant flow (six asthmatics; two control children). For subjects able to perform the OL technique, OL and VC NO measurements were linearly related (r2 = 0.88). In children, VC NO assays are reproducible, sensitive in identifying asthma, and portable. Additionally, we have shown that (1) not all children are able to perform OL measurements, and (2) VC measurements vary linearly with OL measurements. These findings suggest that there may not be compelling reason to favor OL over VC measurements for hypernitrosopnea in children with asthma.

Adolescent↗

Variation between experienced observers in the interpretation of accident and emergency radiographs.

Skill mix and role extension initiatives have highlighted the difficulty of establishing quality standards for the accuracy of plain film reporting. An acceptable performance might be one which is indistinguishable from that of a group of experienced consultant radiologists. In order to assess the feasibility of setting such a standard, the variation between experienced observers must first be established. This study examines the variation found between three observers with the three major types of plain film examination. 402 plain film examinations (205 skeletal, 100 chest and 97 abdominal) performed on accident and emergency patients were reported retrospectively and independently by three experienced radiologists. The clinical data supplied on the request cards were available to the readers. Each examination was categorized by each reader as being normal, as showing significant abnormality relevant to the current clinical problem, or as showing insignificant or irrelevant abnormality. Concordance between all three readers was found in 51%, 61% and 74% of abdominal, chest and skeletal radiographs, respectively. Weighted kappa values confirmed that the level of agreement between pairs of observers was higher with skeletal radiographs (kappa w = 0.76-0.77) than with chest (kappa w = 0.63-0.68), or abdominal (kappa w = 0.50-0.78) examinations. However, the frequency of major disagreements (at least one reader reporting "normal" and one reporting "relevant abnormality") was similar for abdominal (11%), chest (12%) and skeletal (10%) radiographs. When the reports were reclassified into only two groups--either significantly abnormal or not--pairs of observers disagreed on 9-10% of skeletal, 11-19% of chest and 8-18% of abdominal cases. The average incidence of errors per observer was estimated to be in the range 3-6%. The magnitude of interobserver variation in plain film reporting is considerable, and must be taken into account when designing assessment techniques and setting quality standards for this activity.

Bone and Bones↗

Severe aplastic anaemia--complete response to antilymphocyte globulin and cyclosporin.

Severe aplastic anaemia is uniformly fatal unless treated with immunosuppressive therapy or bone marrow transplantation. The latter is curative in 65% of patients and is the treatment of choice in children and young adults. Antilymphocyte globulin (ALG) and cyclosporin may be used successfully in the absence of an HLA matched sibling donor. We report the case of a twelve-year-old boy with severe aplastic anaemia who received immunosuppressive treatment with ALG and cyclosporin and is alive and well three years and six months post treatment.

Anemia, Aplastic↗

The role of automated external defibrillators in rural general practice.

In a questionnaire survey (100% response rate) investigating the availability and use of automated external defibrillators (AEDs), it was found that the success rate (number discharged alive) compared favourably with pre-hospital defibrillation by other providers, and that AEDs aided the management of dysrhythmias not commonly seen in general practice. With appropriate training they are useful in rural general practice.

Data Collection↗

Synthesis and biological activity of lactones en route to Altohyrtin A.

Lactones 2 and 7 were synthesised and tested against six human tumour cell lines (Pancreas-a, BXPC-3), (Thyroid ca, KAT-4), (Thyroid ca, SW1736), (Lung-NSC, NCI-H460), (Pharynx-sq, FADU) and (Prostate, DU-145). Lactone 7 proved inactive, but lactone 2 displayed some activity against four of the six cell lines examined. Both lactones were converted into an intermediate 5 en route to Altohyrtin A.

Antineoplastic Agents↗

Potent inhibitory activities of hydrophobic aci-reductones (2-hydroxytetronic acid analogs) against membrane and human low-density lipoprotein oxidation.

The effects of selected aci-reductones, which are hydrophobic ascorbate-related analogs including 4-chlorophenyl-2-hydroxytetronic acid (Cpd A), 4-(1,1'-biphenyl)-2-hydroxytetronic acid (Cpd B), and 4-(4'-chloro-1,1'-biphenyl)-2-hydroxytetronic acid (Cpd C), on membrane and low density lipoprotein (LDL) oxidation were assessed. Hepatic microsomal lipid peroxidation was induced by the ascorbate + Fe(II) chemical system. All three agents inhibited membrane lipid peroxidation in a concentration-dependent manner with the order of potency: Trolox (vitamin E) < or = Cpd A << Cpd B < Cpd C; based on the EC50 values, Cpd B and Cpd C were 11- and 19-fold, respectively, more potent than Trolox. In contrast to ascorbic acid, all three agents did not display any membrane prooxidative effect in the presence of iron. When human LDL was incubated with 10 microM of Cu(II), LDL oxidation, determined by the formation of thiobarbituric acid reactive substances, followed a typical sigmoidal curve with an initial lag phase. Preincubation of the LDL samples with low micromolar concentrations (1 and 3 microM) of each agents for 30 min before the addition of copper resulted in significant delays of the lag time of LDL oxidation, and the effectiveness of Cpd B and Cpd C was more prominent than that mediated by either Trolox or probucol. Since clinical evidence strongly supports the hypothesis that atherogenesis is initiated by LDL oxidation, the results suggest that these aryl tetronic acid analogs may serve as promising candidates for future therapeutic use as anti-atherogenic agents.

Animals↗

Chemically stabilized trypsin used in dipeptide synthesis.

Bovine pancreatic trypsin was treated with ethylene glycol bis(succinic acid N-hydroxysuccinimide ester). Approximately 8 of 14 lysines per trypsin molecule were modified. This derivative (EG trypsin) was more stable than native between 30 degrees and 70 degrees C: T50 values were 59 degrees C and 46 degrees C, respective. EG trypsin's half-life of 25 min at 55 degrees C was fivefold greater than native's. EG trypsin had a decreased rate of autolysis and retained more activity in aqueous mixtures of 1,4-dioxan, dimethylformamide, dimethylsulfoxide, and acetonitrile. EG trypsin had lower Km values for both amide and ester substrates; its kcat values for two amides (benzoyl-L-arginine p-nitroanilide and benzyloxycarbonyl glycyl-glycyl-arginyl-7-amino-4-methyl coumarin) increased, whereas its kcat value for an ester (thiobenzoyl benzoyloxycarbonyl-L-lysinate) decreased slightly. The specific activity (kcat/Km) of EG trypsin was increased for both amide and ester substrates. EG trypsin gave higher yields and reaction rates than native in kinetically controlled synthesis of benzoyl argininyl-leucinamide in acetonitrile and in t-butanol. Highest peptide yields occurred with EG trypsin in 95% acetonitrile, where 90% of the substrate was converted to product. No peptide synthesis occurred in 95% DMF with either form of trypsin.

Animals↗

Persistent infection of the chin with an unusual skin pathogen (Streptococcus milleri): a sign of intraoral carcinoma.

Streptococcus milleri is a commensal of the oropharynx and gastrointestinal tract which is not generally associated with skin disease. We now report a patient who presented with a pustular mass of the chin with lower lip anaesthesia. He was initially thought to have sycosis barbae, but response to treatment was poor and lesional swabs repeatedly cultured S. milleri. After some delay, squamous cell carcinoma of the mouth, involving the mandible and overlying skin, was detected. We consider that the S. milleri either invaded through the tumour from the mouth or root canal or colonized the skin from saliva dribbled over the numb lower lip. Isolation of an unusual organism and numbness of the chin are features that should suggest the need for early radiography.

Aged↗

Meconium thorax: a case report and review of literature.

A case is presented in which extension of meconium peritonitis through muscular defects in the diaphragm lead to intrathoracic calcifications diagnosed sonographically at 23 weeks of gestation. There were three diaphragmatic defects, two small ones corresponded to foramina of Morgagni and one large posterior defect that did not correspond to the foramen of Bochdelak. There were three additional muscular defects: one in the rectus abdominus and two, bilaterally, in the loins. Despite long-standing fetal ascites and fresh intraperitoneal meconium at laparotomy, postoperative progress was uneventful. The baby did not have other dysmorphic features except for a single palmar crease, the chromosomes were normal, and the baby did not have cystic fibrosis. Follow-up examination at 10 months showed a thriving infant with mild hypotonia and developmental delay, but no respiratory or gastrointestinal problems.

Adult↗

Metallothioneins 1 and 2 have distinct but overlapping expression patterns in Arabidopsis.

The spatial and temporal expression patterns of metallothionein (MT) isoforms MT1a and MT2a were investigated in vegetative and reproductive tissues of untreated and copper-treated Arabidopsis by in situ hybridization and by northern blotting. In control plants, MT1a mRNA was localized in leaf trichomes and in the vascular tissue in leaves, roots, flowers, and germinating embryos. In copper-treated plants, MT1a expression was also observed in the leaf mesophyll and in vascular tissue of developing siliques and seeds. In contrast, MT2a was expressed primarily in the trichomes of both untreated and copper-treated plants. In copper-treated plants, MT2a mRNA was also expressed in siliques. Northern-hybridization studies performed on developing seedlings and leaves showed temporal variations of MT1a gene expression but not of MT2a expression. The possible implications of these findings for the cellular roles of MTs in plants are discussed.

Arabidopsis↗