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Biomedical subjects

B Buckley

Publications and source records attributed to B Buckley.

At least 19 recordsLinked to original sources
PubMed2002

Coeliac disease and autoimmune Addison's disease: a clinical pitfall.

BACKGROUND: Coeliac disease has an increased prevalence in a number of autoimmune endocrine conditions. An association between coeliac disease and Addison's disease has been proposed in isolated case reports, but has not been formally studied. AIM: To investigate the extent of this association. DESIGN: Prospective screening of patients with confirmed Addison's disease. METHODS: From central computerized records, we identified all living patients with a diagnosis of autoimmune Addison's disease in the past 30 years and presently attending our affiliated hospitals. After exclusions, 44 were invited to attend for screening. RESULTS: Of 41 patients screened, five (12.2%) had coeliac disease: Three were previously diagnosed coeliacs and this was confirmed on review, including examination of biopsy material. A further two had positive IgA-endomysial antibodies. Histological confirmation was obtained in both cases. Neither had laboratory or clinical evidence of malabsorption. DISCUSSION: In this series of patients with Addison's disease, a higher co-morbidity with coeliac disease was observed than in any previously studied endocrine condition. We recommend that coeliac serology (anti-endomysial and tissue transglutaminase antibody) testing be incorporated routinely into the autoimmune screen for other conditions in patients with Addison's disease.

Addison Disease↗
PubMed2002

Testing cognitive function in elderly populations: the PROSPER study. PROspective Study of Pravastatin in the Elderly at Risk.

OBJECTIVES: For large scale follow up studies with non-demented patients in which cognition is an endpoint, there is a need for short, inexpensive, sensitive, and reliable neuropsychological tests that are suitable for repeated measurements. The commonly used Mini-Mental-State-Examination fulfils only the first two requirements. METHODS: In the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), 5804 elderly subjects aged 70 to 82 years were examined using a learning test (memory), a coding test (general speed), and a short version of the Stroop test (attention). Data presented here were collected at dual baseline, before randomisation for active treatment. RESULTS: The tests proved to be reliable (with test/retest reliabilities ranging from acceptable (r=0.63) to high (r=0.88) and sensitive to detect small differences in subjects from different age categories. All tests showed significant practice effects: performance increased from the first measurement to the first follow up after two weeks. CONCLUSION: Normative data are provided that can be used for one time neuropsychological testing as well as for assessing individual and group change. Methods for analysing cognitive change are proposed.

Aged↗
PubMed2001

Determination of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) and its metabolite 2-hydroxyamino-PhIP by liquid chromatography/electrospray ionization-ion trap mass spectrometry.

2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic aromatic amine found in cooked meat. It is metabolically activated by the human cytochrome P450 enzymes to form the carcinogenic metabolite N2-OH-PhIP. PhIP has been found to induce tumors in rats and is a suspected human carcinogen. In the present work, we have developed and validated a liquid chromatography-electrospray ionization/ion trap mass spectrometry (LC-ESI/ITMS) method for the determination of PhIP and N2-OH-PhIP. PhIP was incubated with microsomes prepared from the human liver; the PhIP and N2-OH-PhIP formed were isolated from the biomatrices by solid-phase extraction using C18 cartridges, with recoveries greater than 86%. Subsequently, the products were separated on a microbore reversed-phase C18 liquid chromatograph coupled to an ESI-ITMS. The ESI interface and the ITMS were tuned for various parameters, and data acquisition was performed in selective ion monitoring mode. The detection limit of PhIP and N2-OH-PhIP was 1 and 10 pg, respectively. The method is highly sensitive and selective, has simple sample preparation protocols, and should be applicable to the study of the metabolic activation of PhIP in various human tissues.

Chromatography, Liquid↗
PubMed2001

Analysis of urinary metabolites of tea catechins by liquid chromatography/electrospray ionization mass spectrometry.

Tea has been proposed to have beneficial health effects which have been attributed to the polyphenolic compounds known as catechins. The bioavailability and biotransformation of these compounds, however, are not clearly understood. In this study, we used liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) to determine urinary glucuronidated and sulfated tea catechins and their metabolites (including methylated and ring-fission metabolites) based on the detection of deprotonated molecular ions and aglycone fragment ions. The compound resolution was achieved both chromatographically and mass spectroscopically. After green tea administration, the major conjugates appeared in human, mouse, and rat urine samples were identified as monoglucuronides and monosulfates of (-)-epigallocatechin (EGC) and (-)-epicatechin. We also found O-methyl-EGC-O-glucuronides and -O-sulfates and O-methyl-epicatechin-O-sulfates in human urine. (-)-5-(3',4',5'-Trihydroxyphenyl)-gamma-valerolactone (M4) and (-)-5-(3',4'-dihydroxyphenyl)-gamma-valerolactone (M6), the ring-fission metabolites of EGC and (-)-epicatechin, respectively, were also predominantly in monoglucuronide and monosulfate forms in the urine. In comparison to rats, the urinary metabolite profiles of tea catechins in mice resemble more closely to those in humans. This is the first report describing direct simultaneous analysis of multiple tea catechin conjugates in urine samples. This method will allow more thorough investigations of the biotransformation of tea polyphenols.

Adult↗
PubMed2000

An exposure system to study the effects of water-soluble gases on PM-induced toxicity.

An aerosol generation and exposure system to evaluate the role of water-soluble gases in particulate matter (PM)-induced injury was designed, built, and validated by generating test atmospheres to study the role of hydrogen peroxide in PM-induced toxicity. In this system, particle number concentration, size distribution, hydrogen peroxide concentration, and water concentration can all be varied. An ammonium sulfate aerosol with mass median diameter 0.46 +/- 0.01 microm was used as a model atmospheric aerosol because ammonium sulfate is a major component of the fine aerosol, and the water uptake of ammonium sulfate aerosol is well characterized. The following four test atmospheres were generated: (1) ammonium sulfate aerosol, (2) an aerosol containing hydrogen peroxide and ammonium sulfate, (3) vapor-phase hydrogen peroxide, and (4) particle-free air. All test atmospheres were maintained at a relative humidity of 85%. Particle size distribution, number concentration, total hydrogen peroxide concentration, temperature, and relative humidity were measured continuously in the exposure chamber. The gas-particle partitioning of hydrogen peroxide was calculated using total hydrogen peroxide concentration, the Henry's law constant for hydrogen peroxide in water, and aerosol water content. We found that the aerosol generation system produced stable concentrations throughout the 2-hour exposures.

Aerosols↗
PubMed1998

Accumulation of chlorpyrifos on residential surfaces and toys accessible to children.

Quantitative examination of major pathways and routes of exposure to pesticides is essential for determining human risk. The current study was conducted in two apartments and examines the accumulation of the pesticide chlorpyrifos in childrens' toys after the time suggested for reentry after application. It has been established for the first time that a semivolatile pesticide will accumulate on and in toys and other sorbant surfaces in a home via a two-phase physical process that continues for at least 2 weeks postapplication. A summation of the above for a 3-6-year-old child yielded an estimated nondietary total dose of 208 microg/kg/day. Potential exposure from the inhalation pathway was negligible, while dermal and nondietary oral doses from playing with toys contributed to 39 and 61% of the total dose, respectively. If children with high frequency mouthing behavior are considered as candidates for acute exposure to chlorpyrifos residues, the estimated acute dose could be as high as 356 microg/kg/day. Routine reapplication of pesticides could lead to continued accumulation in toys and other sorbant surfaces, e.g., pillows, with large sorbant reservoirs, which can become a long-term source of exposure to a child. Estimates of a child's nondietary exposure to chlorpyrifos associated with toys and other sorbant surfaces for a period of 1 week following application appear to be of public health concern, and studies of actual childhood exposure from this pathway are warranted in the home environment. The above information should be used to determine if current procedures for postapplication reentry are sufficient and to evaluate the need for procedures to store frequently used household toys, pillows, and other sorbant objects during insecticidal application.

Air Pollution, Indoor↗
PubMed1996

Sustained-release morphine sulfate in the management of pain associated with acquired immune deficiency syndrome.

Sustained-release morphine (SRM) was studied in patients with acquired immune deficiency syndrome (AIDS)-related chronic pain. Outpatients and inpatients with AIDS-related pain were studied for 3-18 days in an open-label prospective survey. Patients were stratified according to prior opioid analgesic use for the purposes of initiating and titrating SRM, which was administered at a 12-hr interval. Immediate-release morphine (IRM) was offered every 2 hr as needed for supplemental analgesia at one-quarter to one-third of the 12-hourly SRM dose. Pain intensity (PI), quality of life (QL), acceptability of therapy (AT), side effects, safety, and morphine usage were evaluated. Of 44 patients enrolled, 40 (91%) were evaluable for intent-to-treat analysis, and 24 (55%) completed the study. PI decreased by 50% (from severe to mild-moderate) in the intent-to-treat patients and by 65% (from severe to mild) in the completed patients. QL was fair to good in 80% and poor in 20% of both groups. AT was good to excellent in 78% of the intent-to-treat and in 96% of the completed patients. Of 61 adverse events reported, 61% required intervention, and 92% were resolved. Total morphine dose remained stable while IRM dosage and frequency of use significantly decreased with escalation of the SRM dose. A significant reduction in PI was achievable with SRM in a variety of painful conditions experienced by AIDS patients, with limited or manageable side effects in most. This study supports the usefulness of opioid analgesia for severe pain in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Expression of tobacco ringspot virus capsid protein and satellite RNA in insect cells and three-dimensional structure of tobacco ringspot virus-like particles.

The capsid protein gene of tobacco ringspot virus (TobRV), which had been modified to contain an amino-terminal methionine codon, was ligated into a baculovirus transfer vector downstream from the polyhedrin promoter. The resulting plasmid was cotransfected with linearized baculovirus DNA into insect cells. Recombinant baculovirus expressed high levels of the TobRV capsid protein that assembled to form virus-like particles that were similar in size and shape to authentic TobRV capsids. These virus-like particles did not encapsidate any RNA, including the capsid protein mRNA. The capsid protein mRNA is a truncated RNA 2, which may lack a putative encapsidation signal. To determine whether an intact packaging substrate could be encapsidated by the TobRV capsid protein, another recombinant baculovirus, concomitantly expressing both capsid protein and TobRV satellite RNA, was constructed. Surprisingly, the vast majority of the satellite RNA molecules expressed from this recombinant baculovirus were ligated in the insect cells to form circular RNA molecules. Like circular forms of satellite RNA generated in planta, these circular satellite molecules remained unencapsidated by the TobRV capsid protein. Computer-generated three-dimensional reconstruction using electron cryomicrographs of the empty virus-like particles allowed the first structural analyses of any nepovirus capsid. This 22-A resolution reconstruction resembled capsids of other members of the picornavirus superfamily. These data support the hypothesis that the nepovirus capsid is structurally analogous to those of the como- and picornaviruses.

Animals↗
PubMed1995

Osteopenia, abnormal dentition, hydrops fetalis and communicating hydrocephalus.

We describe a single male infant who developed severe hydrops fetalis between 19 and 28 weeks of gestation. After delivery at 32 weeks he was treated by hemofiltration, prolonged ventilation and intravenous feeding. He had hypertelorism, orbital hypoplasia without proptosis, brachydactyly, frontal and temporal bossing of the skull, central hypotonia, communicating hydrocephalus, and severe delay in psychomotor development. Signs of connective tissue disorder included: osteopenia, pathological fracture, yellow/grey discolored teeth, blue sclerae and easy bruising. Laboratory investigations failed to reveal the cause of fetal hydrops or collagen abnormality. His mother and one sib had learning difficulties. Although some of these findings may be due to perinatal factors, the connective tissue abnormalities suggest a genetic syndrome in the heterogeneous group of osteogenesis imperfecta. This case either represents the more severe end of the spectrum of Type IV osteogenesis imperfecta or the mild end of the spectrum of Cole-Carpenter syndrome.

Bone Diseases, Metabolic↗
PubMed1993

Nucleotide sequence and in vitro expression of the capsid protein gene of tobacco ringspot virus.

The nucleotide sequence of the 3' terminal 2022 nucleotides (nt) of tobacco ringspot virus (TobRV) RNA 2 has been determined. Protein microsequence analysis of the amino-terminal residues of purified capsid protein localized the capsid protein gene between nt 2014 and 583 (from the 3' terminus) of this sequence. The proteolytic cleavage site that is processed to liberate the capsid protein from the RNA 2-encoded polyprotein was identified as Cys-Ala. The predicted translation product from the gene is a 477 amino acid long polypeptide with a calculated MW of 53 kDa. The gene was modified at the 5' end to facilitate sub-cloning, and to provide it with a methionine initiation codon. The modified gene was sub-cloned, transcribed in vitro and expressed in a rabbit reticulocyte lysate translation system, where it directed the synthesis of a 53 kDa polypeptide. Garnier-Osguthorpe-Robson analyses of the secondary structure of the capsid protein predicted the presence of three beta sheet domains, which suggests that this nepovirus capsid may be structurally analogous to those of the como- and picornaviruses. These and other results from computer analyses of the nucleic acid and amino acid sequences, and comparisons with the capsid proteins of nepoviruses and other related viruses are discussed.

Amino Acid Sequence↗
PubMed1993

Local administration of EAA antagonists blocks light-induced phase shifts and c-fos expression in hamster SCN.

Syrian hamsters were fitted with guide cannulas stereotaxically aimed at the suprachiasmatic nuclei (SCN) and housed in constant darkness in cages equipped with running wheels. Animals received 300-nl injections of either vehicle, CNQX, or MK-801 into the region of the SCN 5 min before a brief (10 min at 20 lx) light exposure. Local administration of either 1 mM CNQX or 1 mM MK-801 at circadian time (CT) 18 significantly inhibited light-induced phase advances (vehicle = 52 +/- 9 min; CNQX = 12 +/- 7 min; MK-801 = 12 +/- 5 min; P < 0.05 relative to vehicle+light group). The effects of both drugs were reversible and dose related. Injection of 1 mM MK-801 at CT13.5 resulted in a 71% inhibition of light-induced phase delays (vehicle = -51 +/- 6 min; MK-801 = -15 +/- 5 min; P < 0.05), while CNQX failed to significantly inhibit light-induced phase delays (-39 +/- 10 min). Local administration of either 1 mM CNQX or MK-801 into the SCN region reduced the number of Fos-immunoreactive cells relative to vehicle-injected controls by approximately 32 and 44%, respectively (vehicle = 951 +/- 79; CNQX = 643 +/- 135, P < 0.05; MK-801 = 533 +/- 143, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1993

Metabolism of apoB-100-containing lipoproteins in familial hyperchylomicronemia.

The metabolism of apolipoprotein B-100 was studied in three patients with familial hyperchylomicronemia (type I hyperlipoproteinemia) using a very low density lipoprotein (VLDL) dual-tracer technique. Radioiodinated VLDL1 (Sf 60-400) and VLDL2 (Sf 20-60) were injected and their catabolism and rate of the transfer of apoB into VLDL2, intermediate density lipoprotein (IDL) (Sf 12-20), and low density lipoprotein (LDL) (Sf 0-12) were compared in patients and in five normolipidemic controls. The rates of delipidation of large triglyceride-rich VLDL1 to VLDL2 (0.26-0.54 pools/day vs. 2.5-5.2 pools/day in controls) and VLDL1 direct catabolism (0.33-0.92 pools/day vs. 4.2-14.7 pools/day in controls) were found to be significantly reduced in type I patients resulting in a tenfold increase of VLDL1 pool size. ApoB synthesis into this density interval was, however, normal as was that into smaller VLDL2. the circulating apoB mass in VLDL2 was not increased. In fact, apart from a modest decrease in the rate of VLDL2 delipidation to IDL and LDL, the behavior of apoB in this density interval was similar in hyperchylomicronemic and normal subjects. Likewise, the transfer of apoB through the IDL and LDL density ranges was not significantly different from normal. Pool sizes of these fractions, however, were reduced, the latter significantly (354-491 mg vs. 1,160-2,505 mg in controls) due to increased direct catabolism in hyperchylomicronemic patients. The results of this study indicate that lipoprotein lipase deficiency primarily affects VLDL1 metabolism, both its delipidation and direct removal from plasma. Lipolysis further down the delipidation cascade is not dependent on this enzyme. Hypercatabolism rather than a failure of synthesis of IDL and LDL was responsible for the decreased pools for both lipoproteins.

Adult↗
PubMed1992

Characterization of antibodies against methyl-pppN cap structure: plant U3 small nucleolar RNA is recognized by these antibodies.

In eukaryotes, many small nuclear RNAs contain either a trimethylguanosine cap structure of a gamma-monomethyl (me) cap structure. Previously, we reported the characterization of anti-mepppG antibodies which recognize methyl-capped RNAs with G as the initiation nucleotide. We report here the preparation of antibodies against mepppN cap structure. Anti-mepppN antibodies recognized only mepppN from a mixture of mepppN and pppN and immunoprecipitated mepppA-capped U3 small nucleolar RNA from a mixture of cowpea cell RNAs. These anti-mepppN antibodies recognized methylated nucleoside triphosphates (mepppA, mepppC, mepppG and mepppU) with nearly equal efficiency; however, these antibodies did not recognize methyl phosphate or methylated mononucleotides. These antibodies will be useful in the identification and characterization of all methyl-capped RNAs no matter which is the initiation nucleotide.

Antibodies, Antinuclear↗