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Biomedical subjects

R Green

Publications and source records attributed to R Green.

At least 91 records · Page 5Linked to original sources
PubMed1999

Normalization of hyperhomocysteinemia with L-thyroxine in hypothyroidism.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for coronary, peripheral, and cerebrovascular disease. Elevated plasma homocysteine levels were described in a preliminary report on primary hypothyroidism. OBJECTIVE: To determine whether restoration of euthyroidism by L-thyroxine replacement therapy would reduce or normalize plasma homocysteine levels. DESIGN: Prospective cohort study. SETTING: Outpatient endocrinology department of a tertiary center. PATIENTS: 14 patients (10 women and 4 men; 25 to 77 years of age): 4 with newly diagnosed chronic (Hashimoto) hypothyroidism and 10 who had been rendered acutely hypothyroid (thyroid-stimulating hormone level > 25 mU/L) by total thyroidectomy for thyroid carcinoma. MEASUREMENTS: Total plasma homocysteine levels were measured at baseline and 3 to 9 months later, after euthyroidism had been attained by L-thyroxine replacement therapy. RESULTS: Median baseline plasma homocysteine levels in both sexes (women, 11.65 micromol/L [range, 7.2 to 26.5 micromol/L]; men, 15.1 micromol/L [range, 14.1 to 16.3 micromol/L]) were higher (P = 0.002) than those in healthy female (n = 35) and male (n = 36) volunteers (women, 7.52 micromol/L [range, 4.3 to 14.0 micromol/L]; men, 8.72 micromol/L [range, 5.94 to 14.98 micromol/L]). Eight patients (57%) had baseline plasma homocysteine levels that exceeded the upper limit of sex-specific reference ranges. Upon attainment of euthyroidism, all patients had a diminution in plasma homocysteine levels. The median overall change of -5.5 micromol/L (range, -15.4 to -1.8 micromol/L) corresponds to a difference of -44% (range, -58% to -13%) (P < 0.001). Homocysteine levels returned to normal in 7 of the 8 patients with elevated pretreatment values. CONCLUSIONS: Hypothyroidism may be a treatable cause of hyperhomocysteinemia, and elevated plasma homocysteine levels may be an independent risk factor for the accelerated atherosclerosis seen in primary hypothyroidism.

Adult↗
PubMed1999

Reconstitution of functional 50S ribosomes from in vitro transcripts of Bacillus stearothermophilus 23S rRNA.

In vitro transcripts of Bacillus stearothermophilus 23S rRNA can be reconstituted into catalytically active 50S ribosomal subunits with an efficiency only 3-4-fold lower than that of natural 23S rRNA. Thus, post-transcriptional modifications in 23S rRNA are not essential for the assembly or function of the 50S subunit of the ribosome. This reconstitution sytem has been used to characterize the peptidyl transferase activity of site-directed mutations in 23S rRNA at positions G2252, U2506, U2584, and A2602 (Escherichia coli numbering), demonstrating its potential for the analysis of the role played by 23S rRNA in the function of the 50S subunit of the ribosome.

Adenosine↗
PubMed1999

The effect of continuous drug exposure on the immune response to Trichostrongylus colubriformis in sheep.

The effect of albendazole (ABZ)-capsule (CRC) administration on parasite establishment and immunity to ABZ-resistant (RES) and -susceptible (SUS) T. colubriformis was measured in Romney lambs. During 12 weeks of twice-weekly dosing with 3000 parasite larvae (L3), eggs were observed in faeces from CRC-treated and untreated lambs given RES L3, but not CRC-treated lambs given SUS L3. Following the period of trickle challenge all lambs were drenched and, 1 week later, dosed with 20000 SUS L3. Resulting worm burdens were higher in control lambs than in those previously treated with CRCs and challenged with SUS, which in turn were higher than those in the CRC-treated or -untreated lambs previously challenged with RES L3. During the period of trickle challenge, the number of peripheral eosinophils and titres of anti-L3 and anti-adult antibody were raised only in those groups given RES L3. There was no effect of CRC administration. Following drench and challenge, antibody titres and eosinophil numbers increased in the control animals but not in those groups which had received previous trickle infection. The results demonstrate that the larval challenge alone resulted in incomplete though substantial protection against subsequent parasite challenge. The use of CRCs may potentially impact on subsequent animal performance and selection for anthelmintic resistance through a reduced level of immunity.

Albendazole↗
PubMed1999

Characterization of functionally active subribosomal particles from Thermus aquaticus.

Peptidyl transferase activity of Thermus aquaticus ribosomes is resistant to the removal of a significant number of ribosomal proteins by protease digestion, SDS, and phenol extraction. To define the upper limit for the number of macromolecular components required for peptidyl transferase, particles obtained by extraction of T. aquaticus large ribosomal subunits were isolated and their RNA and protein composition was characterized. Active subribosomal particles contained both 23S and 5S rRNA associated with notable amounts of eight ribosomal proteins. N-terminal sequencing of the proteins identified them as L2, L3, L13, L15, L17, L18, L21, and L22. Ribosomal protein L4, which previously was thought to be essential for the reconstitution of particles active in peptide bond formation, was not found. These findings, together with the results of previous reconstitution experiments, reduce the number of possible essential macromolecular components of the peptidyl transferase center to 23S rRNA and ribosomal proteins L2 and L3. Complete removal of ribosomal proteins from T. aquaticus rRNA resulted in loss of tertiary folding of the particles and inactivation of peptidyl transferase. The accessibility of proteins in active subribosomal particles to proteinase hydrolysis was increased significantly after RNase treatment. These results and the observation that 50S ribosomal subunits exhibited much higher resistance to SDS extraction than 30S subunits are compatible with a proposed structural organization of the 50S subunit involving an RNA "cage" surrounding a core of a subset of ribosomal proteins.

Peptidyl Transferases↗
PubMed1999

The identical 5' splice-site acceptor mutation in five attenuated APC families from Newfoundland demonstrates a founder effect.

Inherited mutations of the APC gene predispose carriers to multiple adenomatous polyps of the colon and rectum and to colorectal cancer. Mutations located at the extreme 5' end of the APC gene, however, are associated with a less severe disease known as attenuated adenomatous polyposis coli (AAPC). Many individuals with AAPC develop relatively few colorectal polyps but are still at high risk for colorectal cancer. We report here the identification of a 5' APC germline mutation in five separately ascertained AAPC families from Newfoundland, Canada. This disease-causing mutation is a single basepair change (G to A) in the splice-acceptor region of APC intron 3 that creates a mutant RNA without exon 4 of APC. The observation of the same APC mutation in five families from the same geographic area demonstrates a founder effect. Furthermore, the identification of this germline mutation strengthens the correlation between the 5' location of an APC disease-causing mutation and the attenuated polyposis phenotype.

Adenomatous Polyposis Coli↗
PubMed1999

Homocysteine metabolism in cardiovascular cells and tissues: implications for hyperhomocysteinemia and cardiovascular disease.

We have determined the activity and protein levels of CBS in a number of cardiovascular cells and tissues by direct enzyme assay and Western blot analysis, respectively. We have also determined the activity of BHMT in these same tissues and cells and have come to the conclusion that neither enzyme is expressed. This results suggests that in the human cardiovascular system homocysteine metabolism is limited to the remethylation pathway catalyzed by MS. Thus, hyperhomocysteinemia in conjunction with a limited metabolic capacity for homocysteine in the cardiovascular system could result in cellular dysfunction.

Animals↗
PubMed1999

Washing the dog reduces dog allergen levels, but the dog needs to be washed twice a week.

BACKGROUND: Many asthmatic patients allergic to dogs refuse to part with their dog, and it is essential to develop techniques for lowering exposure with a dog in the home. OBJECTIVE: This study investigated the effect of dog washing on the subsequent recovery of Can f 1 from dog hair clippings and on the airborne allergen over a 7-day period. METHODS: Dogs, which had not been washed for at least the previous 3 weeks, were washed with a hand-held shower and proprietary shampoo. Hair clippings and dander samples from 25 dogs were collected before and immediately after washing. After these initial studies, 16 dogs had a small tuft of hair clipped from the collar or spinal area before washing and then daily for the next 7 days. Air sampling was performed in 5 homes, and the air samples were collected (airflow rate, 9 L/min) over an 8-hour period per day on 10 consecutive days (3 days of baseline sampling before washing and then 7 consecutive days after washing). Can f 1 level was measured by using 2-site ELISA. RESULTS: Washing significantly reduced recoverable Can f 1 from clippings (84% reduction: from 73 microg/g to 12 microg/g [geometric mean]; P <.0001) and from dander samples (86% reduction: from 347 microg/g to 50 microg/g [geometric mean]; P <.0001). There was a significant reduction in Can f 1 levels in dog hair over the observed 8-day period (F = 18.4, P <. 0001). By using a multiple comparison test, this observed significance was found to be due to the difference between the baseline levels and those on days 1 and 2 after washing, with no difference in the baseline Can f 1 compared with days 3 to 7. Airborne Can f 1 levels showed a downward trend, which reached statistical significance when the data were grouped into 3 sampling periods as follows: baseline (ie, mean of 3 days before sampling) was compared with days 1 to 4 after washing (41% reduction, 95% CI 13%-60%) and days 5 to 7 after washing (61% reduction, 95% CI 2%-84%; P =.014). CONCLUSIONS: Washing the dog reduces recoverable allergen from dog hair and dander. The dog needs to be washed at least twice a week to maintain the reduction in recoverable Can f 1 from its hair. Washing the dog achieves a modest reduction in the level of airborne Can f 1 in homes with a dog.

Air Pollution, Indoor↗
PubMed1999

Base-pairing between 23S rRNA and tRNA in the ribosomal A site.

The aminoacyl (A site) tRNA analog 4-thio-dT-p-C-p-puromycin (s4TCPm) photochemically cross-links with high efficiency and specificity to G2553 of 23S rRNA and is peptidyl transferase reactive in its cross-linked state, establishing proximity between the highly conserved 2555 loop in domain V of 23S rRNA and the universally conserved CCA end of tRNA. To test for base-pairing interactions between 23S rRNA and aminoacyl tRNA, site-directed mutations were made at the universally conserved nucleotides U2552 and G2553 of 23S rRNA in both E. coli and B. stearothermophilus ribosomal RNA and incorporated into ribosomes. Mutations at G2553 resulted in dominant growth defects in E. coli and in decreased levels of peptidyl transferase activity in vitro. Genetic analysis in vitro of U2552 and G2553 mutant ribosomes and CCA end mutant tRNA substrates identified a base-pairing interaction between C75 of aminoacyl tRNA and G2553 of 23S rRNA.

2-Aminopurine↗
PubMed1999

Chemoinformatics--a new name for an old problem?

Library chemistry and high-throughput screening require greater use of chemoinformatics to increase their effectiveness. Recent advances in chemoinformatics include new molecular descriptors and pharmacophore techniques, statistical tools and their applications. Visualisation methods and hardware development are also opening new opportunities. The advent of a chemically aware web language and cross-platform working is ensuring that chemoinformatics methods are becoming available to all chemists in a more appropriate manner. Much time will continue to be wasted with incompatible file types without internationally agreed standards.

Chemical Phenomena↗
PubMed1999

The effect of air filtration on airborne dog allergen.

BACKGROUND: Effective methods of reducing dog allergen are required to help alleviate symptoms in asthmatic patients sensitized to dog who refuse to part with their pet. The aim of this study was to investigate the use of the high efficiency particulate air (HEPA) filter air cleaner to reduce airborne Can f 1 in homes with a dog. METHODS: The effect of a HEPA air cleaner was investigated in nine homes with a dog. Samples were collected from two rooms of each house concurrently, one of which contained the dog, on two separate days (active day - HEPA air cleaner on - and control day). Eight consecutive 1-h samples were collected from each room with a high-volume air sampler (airflow rate 60 l/ min). Can f 1 was determined by monoclonal-polyclonal antibody-based ELISA. RESULTS: Baseline airborne Can f 1 levels were 3.8-fold greater when sampling was performed with a dog in the room (GM 27.1 ng Can f 1/m3, range 2.63-329) than when the dog was elsewhere in the house (GM 7.1 ng Can f 1/m3, range 0.69-27.2). When the dog was elsewhere in the house, airborne Can f 1 levels fell on both active and control days, but the magnitude of the reduction was significantly greater on the active days (P<0.05), and was approximately 90% from baseline. With the dog in the room, a significant fall in airborne Can f 1 was observed only on active days (75% from baseline), but not on control days (active vs control P<0.001). CONCLUSIONS: HEPA air cleaners reduce airborne Can f 1 in homes with dogs. Furthermore, preventing the access of the dog to the bedroom and possibly the living room may reduce the total allergen load inhaled.

Air Pollution, Indoor↗
PubMed1999

The ribosome revealed.

Several recently reported structures reveal the details of ribosome architecture and provide new insights into the mechanism of protein synthesis.

Bacterial Proteins↗
PubMed1999

Perinatal aspects of inherited thrombophilia.

The identified main causes of inherited thrombophilia are deficiencies of antithrombin, protein C and protein S, activated protein C (APC) resistance and the factor V Leiden mutation, mutant factor II, and inherited hyperhomocysteinemia. In women from symptomatic families these defects may be associated with an increased risk of venous thrombosis in pregnancy and recurrent fetal loss. Inherited thrombophilia is common and appears to be a multigene disorder. The thrombotic risk would seem to be greatest in women with antithrombin deficiency and more than one thrombophilia defect. The abnormalities that are now recognized represent only part of the genetic predisposition to thrombosis. In assessing thrombotic risk in pregnancy, acquired risk factors as well as genetic predisposition should be considered. Increasing age, obesity, immobility, and delivery by cesarean section are major risk factors. Pregnancy should be planned, and each patient should be managed on an individual basis. In pregnancy, heparin is the anticoagulant of choice, and as far as possible, treatment with warfarin should be avoided because of the risks to the fetus. When patients are on long-term treatment with warfarin, pregnancy should be avoided, and warfarin should be discontinued prior to embarking on a pregnancy or as soon as pregnancy is suspected and before 6 weeks' gestation. In women from symptomatic families with antithrombin deficiency, adjusted dose heparin throughout pregnancy is recommended and warfarin for at least 3 months post partum. In protein C and protein S deficiency, factor V Leiden, or mutant factor II, treatment can be based on personal and family history. Thromboprophylaxis in late pregnancy and post partum should be considered. Fetal loss may be increased in women with inherited thrombophilia. The risk appears greatest in women with antithrombin deficiency and women with more than one thrombophilia defect. A number of reports have claimed that prophylactic treatment with heparin during pregnancy has resulted in successful pregnancy in women with recurrent fetal death and inherited thrombophilia.

Family Health↗
PubMed1999

Serum cobalamin, homocysteine, and methylmalonic acid concentrations in a multiethnic elderly population: ethnic and sex differences in cobalamin and metabolite abnormalities.

BACKGROUND: Low cobalamin concentrations and mild hyperhomocysteinemia are common in the elderly but ethnic differences have not been defined. OBJECTIVE: Our objective was to determine the demographic characteristics of cobalamin deficiency in the elderly and its role in their hyperhomocysteinemia. DESIGN: We measured serum cobalamin, total homocysteine (Hcys), and methylmalonic acid (MMA) concentrations in 725 subjects >60 y old, and folate concentrations in 520 subjects. RESULTS: After exclusion of subjects taking cobalamin supplements or with renal insufficiency, high prevalences of low cobalamin (11.8%), high MMA (16.6%), and high Hcys (26.1%) concentrations were seen. Most cobalamin concentrations <140 pmol/L appeared to reflect deficiency because 78. 3% of them were accompanied by abnormal metabolites. Subjects with cobalamin concentrations of 140-258 pmol/L had significantly fewer metabolic abnormalities. A low cobalamin concentration and renal insufficiency were the strongest predictors of abnormal Hcys concentrations. Elderly men had higher Hcys concentrations than did women (P = 0.0001). Whites and Latin Americans had lower cobalamin concentrations than did blacks and Asian Americans (P < 0.005). Whites also had higher Hcys concentrations than all the other groups (P < 0.05). When included in the analysis, renal insufficiency in subjects was associated with 23.8% of all high Hcys and 25.5% of all high MMA concentrations; most with renal insufficiency were Asian American and black men. CONCLUSIONS: Mild cobalamin deficiency is most common in elderly white men and least common in black and Asian American women. Hyperhomocysteinemia, which is most strongly associated with low cobalamin concentrations, is also most common in elderly whites, whereas that associated with renal insufficiency is more common in blacks and Asian Americans. Ethnic differences in cobalamin deficiency and the Hcys patterns associated with it or with renal insufficiency warrant consideration in supplementation strategies. Extending suspicion of deficiency to persons with cobalamin concentrations of 140-258 pmol/L appears to provide more disadvantages than advantages.

Aged↗