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Biomedical subjects

A Bird

Publications and source records attributed to A Bird.

At least 109 records · Page 6Linked to original sources
PubMed1991

DNA methylation and chromatin structure.

Studies of the whole genome by molecular and cytogenetic methods have implicated DNA methylation in the formation of 'inactive chromatin'. This has been confirmed by analysis of specific endogenous sequences, and has been mimicked by introducing methylated and non-methylated sequences into cells. As well as affecting chromatin structure. DNA methylation also represses transcription. A protein (MeCP) which binds specifically to methylated DNA has been identified. The properties of MeCP could account for the effects of DNA methylation on both chromatin and transcription.

5-Methylcytosine↗
PubMed1991

Non-methylated islands in fish genomes are GC-poor.

In the vertebrate genomes studied to date the 5' end of many genes are associated with distinctive sequences known as CpG islands. CpG islands have three properties: they are non-methylated; the dinucleotide CpG occurs at the frequency predicted by base composition; and they are GC-rich. Unexpectedly we have found that CpG islands in certain fish only have the first two properties; that is, their GC-content is not elevated compared to bulk genomic DNA. Based on this finding, we speculate that the GC-richness of CpG islands in vertebrates other than fish is a passive consequence of a higher mutation rate in regions of open chromatin under conditions where the nucleotide precursor pools are biased.

Actins↗
PubMed1991

DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein.

We have studied the mechanism by which DNA methylation inhibits transcription both in cell-free nuclear extracts and in the living cell. Repression of transcription in vitro for four different promoters was shown to be an indirect effect. The mediator of repression had properties indistinguishable from those of a methyl-CpG binding protein (MeCP-1) that has been previously identified. Use of differentially methylated promoters and methylated competitors in transient transfection assays suggested that indirect repression via MeCP-1 also occurs in the living cell. This was supported by the fact that MeCP-1-deficient cells showed much reduced repression of methylated genes.

Animals↗
PubMed1990

High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines.

CpG islands are normally methylation free in cells of the animal, even when the associated gene is transcriptionally silent. In mouse NIH 3T3 and L cells, however, over half of the islands are heavily methylated. Near identity of the methylated subset in the two cell lines suggested that methylation is confined to genes that are nonessential in culture. In agreement with this, islands at several tissue-specific genes, but not at housekeeping genes, have become methylated in many human and mouse cell lines. At the chromatin level, methylated islands are Mspl resistant compared with their nonmethylated counterparts. We suggest that mutation-like gene inactivation due to CpG island methylation is widespread in many cell lines and could explain the loss of cell type-specific functions in culture.

Animals↗
PubMed1990

Alternative chromatin structure at CpG islands.

Actively transcribed chromatin is structurally different from bulk inactive chromatin. It has been difficult to define the molecular basis of the difference, however, because purified fractions of active chromatin were not available. We have overcome this problem by releasing oligonucleosomes from the nonmethylated CpG-rich islands (CpG islands) of HeLa cell nuclei using restriction endonucleases. Since CpG islands very often include the promoters and 5' transcribed regions of genes, they represent a model for the "active" chromatin structure. CpG island chromatin differs in three respects from bulk chromatin prepared in the same way: histone H1 is present in very low amounts; histones H3 and H4 are highly acetylated; and nucleosome-free regions are present. Except for the latter regions, the average nucleosomal spacing is similar to that of bulk chromatin.

Base Sequence↗
PubMed1990

A multiple dose pharmacokinetic and tolerance study of once daily 200 mg sustained-release flurbiprofen capsules in young and very elderly patients.

The pharmacokinetic profile of 200 mg sustained-release flurbiprofen capsules was compared in nine elderly (mean age 84.2 years) and 10 young (mean age 38.1 years) patients with arthritis. After a single capsule, a 48 h plasma concentration profile was performed. The patients then took 1 capsule daily for a further 13 days with plasma levels of the drug being measured pre-dose on alternate days. Following ingestion of the last capsule, a further 48 hour plasma concentration profile was performed. These results were compared with each other and with computer predicted data obtained from dosing with 200 mg conventional flurbiprofen (as 100 mg b.d.). In both young and elderly patients, the two 48 h plasma concentration profiles confirmed the sustained-release characteristics of the capsule. There was no evidence of dose-dumping, although, in one elderly patient with a partial gastrectomy, higher plasma concentrations were observed. Inter- and intra-patient variability was acceptable. A steady-state was achieved within the predicted four days in both groups and there was no evidence of accumulation with the daily dosing interval. A mean steady-state level of approximately 6 micrograms/ml was achieved for both populations. Computer predicted data for 200 mg conventional flurbiprofen (as 100 mg b.d.) showed a pre-dose/peak range of 1-12 micrograms/ml. The pre-dose/peak ranges for the young and old patients were 4-10 micrograms/ml and 4-8 micrograms/ml respectively. One young patient developed a hypersensitivity reaction of moderate severity; one young and four elderly patients developed a low haemoglobin concentration during the study. No other changes in haematological or biochemical parameters were seen.

Adult↗
PubMed1990

The Iowa Articulation Norms Project and its Nebraska replication.

The purpose of the Iowa Articulation Norms Project and its Nebraska replication was to provide normative information about speech sound acquisition in these two states. An assessment instrument consisting of photographs and a checklist form for narrow phonetic transcription was administered by school-based speech-language pathologists to stratified samples of children in the age range 3-9 years. The resulting data were not influenced by the demographic variables of population density (rural/urban), SES (based on parental education), or state of residence (Iowa/Nebraska); however, sex of the child exerted a significant influence in some of the preschool age groups. The criteria used to determine acceptability of a production appeared to influence outcomes for some speech sounds. Acquisition curves were plotted for individual phoneme targets or groups of targets. These curves were used to develop recommended ages of acquisition for the tested speech sounds, with recommendations based generally on a 90% level of acquisition. Special considerations were required for the phonemes /ng s z/.

Age Factors↗
PubMed1990

The expected equilibrium of the CpG dinucleotide in vertebrate genomes under a mutation model.

The CpG dinucleotide is present at approximately 20% of its expected frequency in vertebrate genomes, a deficiency thought due to a high mutation rate from the methylated form of CpG to TpG and CpA. We examine the hypothesis that the 20% frequency represents an equilibrium between rate of creation of new CpGs and accelerated rate of CpG loss from methylation. Using this model, we calculate the expected reduction in the equilibrium frequency of the CpG dinucleotide and find that the observed CpG deficiency can be explained by mutation from methylated CpG to TpG/CpA at approximately 12 times the normal transition rate, the exact rate depending on the ratio of transitions to transversions. The observed rate of CpG dinucleotide loss in a human alpha-globin nonprocessed pseudogene, psi alpha 1, and the apparent replenishment of the CpG pool in this sequence by new mutations, agree with the above parameters. These calculations indicate that it would take 25 million years or less, a small fraction of the time for vertebrate evolution, for CpG frequency to be reduced from undepleted levels to the current depleted levels.

Animals↗
PubMed1990

Indomethacin for patent ductus arteriosus closure. Application of serum concentrations and pharmacodynamics to improve response.

Indomethacin dosing for patent ductus arteriosus closure has been standardized despite wide interpatient variability in indomethacin pharmacokinetics. We compared a novel indomethacin dosing approach using individual pharmacokinetic and pharmacodynamic information (group A) with a control group from our institution (group B) and a level 3 university-based intensive care nursery (group C) who were dosed using current dosing guidelines. Permanent patent ductus arteriosus closure was achieved in 27 of 28 (96.4%) group A patients, 10 of 16 (62.5%) group B patients, and 7 of 13 (52.8%) group C patients. Success rates were significantly higher in group A than Groups B and C (P less than .02). Renal toxicity was the only toxicity reported in any group. The major manifestations of renal toxicity, ie, urine output below 1 mL/kg/h or increased serum creatinine by greater than or equal to 0.5 mg/dL, occurred in none of the group A patients but in seven (43.8%) group B and eight (61.5%) group C patients. Renal toxicity was significantly greater in groups B and C than group A (P less than .02). A pharmacodynamic concentration versus response curve was developed and proved predictive of patent ductus arteriosus closure rates in previous studies where indomethacin concentration versus response data were available. Serum concentration monitoring is a valuable adjunct to indomethacin therapy for patent ductus arteriosus closure, especially when a pharmacodynamic approach is used.

Algorithms↗
PubMed1989

Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro.

Interleukin-1 (IL-1) alpha and beta and tumor necrosis factor (TNF) alpha and beta are potent stimulators of bone resorption in vitro and in vivo. However, the mechanisms underlying this increased bone resorption have not been clearly defined. Increased bone resorption can result from increased activity of individual osteoclasts, increased numbers of osteoclasts, or both. Therefore, we have used a long-term human marrow culture system that forms multinucleated cells (MNC) with the characteristics of osteoclasts to examine the effects of IL-1 and TNF on osteoclast formation. Human recombinant IL-1 alpha and IL-1 beta, and human recombinant TNF-alpha and TNF-beta stimulated MNC formation from 4- to 60-fold. IL-1 alpha, IL-1 beta, TNF-alpha, and TNF-beta significantly increased MNC formation at very low concentrations: 2.5 x 10(-13) M for IL-1 alpha and IL-1 beta, 10(-11) M for TNF-alpha, and 10(-10) M for TNF-beta In addition, these cytokines enhanced MNC formation in the presence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], a potent osteotropic factor that stimulates MNC formation by stimulating fusion of mononuclear precursor cells. Simultaneous addition of IL-1 and TNF to the cultures resulted in a synergistic stimulation of MNC formation. These results suggest that: (1) IL-1 and TNF stimulate bone resorption in part by increasing osteoclast formation and (2) an extremely low concentration of these factors can synergistically increase osteoclast formation in the absence of other factors, such as 1,25-(OH)2D3. These data suggest that synergistic interactions among cytokines play an important role in maintaining bone cell activity in normal and pathologic states.

Bone Resorption↗
PubMed1989

Identification of blast cells in the peripheral blood of patients with acute leukaemia using the Technicon H-1.

The Technicon H-1 counter represents a refinement of the cytochemistry-based technology of its predecessors, the H6000 and the Hemalog-D. It also has a new channel, the basophil-lobularity channel, which is said to enhance the sensitivity of leukaemic blast detection in comparison with previous instruments. To evaluate this facility, 35 adult patients with acute leukaemia at different phases of their disease were monitored for the presence of circulating leukaemic blasts during a 4-week period. The ability of the H-1 to detect blasts was compared to a careful manual review of a blood and bone marrow smear. Using the latter review as the standard, the sensitivity was 83.8% with a specificity of 78%. Exclusion of patients with severe leucopenia (less than 1.0 x 10(9)/l) increased the specificity to 89%, with little alteration in the sensitivity. We were unable to confirm the high degree of sensitivity claimed in previous reports. The H-1 blast flag, however, would appear useful for screening patients who are off therapy or on maintenance regimens.

Blast Crisis↗
PubMed1989

Osteoclast-like cells form in long-term human bone marrow but not in peripheral blood cultures.

Transplantation studies have suggested that peripheral blood mononuclear cells contain precursors for osteoclasts. Thus we tested the capacity of peripheral blood monocytes to form osteoclasts in long-term culture. We have reported previously that mononuclear cells from feline, baboon, and human marrow form osteoclast-like cells in long term cultures. Further, the formation of these cells is increased in response to bone resorption stimulatory agents such as PTH, interleukin 1, and transforming growth factor alpha. We now report that these cells show characteristic cytoplasmic contraction with calcitonin and form resorption lacunae when cultured on sperm whale dentine. Thus, these bone marrow-derived multinucleated cells fulfill the functional criteria for osteoclasts. Although cultured peripheral blood monocytes can be induced to form multinucleated cells with 1,25-dihydroxyvitamin D3, these cells did not show similar responses to the osteotropic factors as multinucleated cells formed in the bone marrow cultures multinucleated cells. These results indicate that osteoclasts or cells closely related to osteoclasts form in long-term human bone marrow cultures. In contrast, few mononuclear cells in the peripheral blood appear capable of forming osteoclasts under the culture conditions used in these experiments.

Bone Marrow↗
PubMed1988

Zulu XX/XX dispermic chimaera from Natal with two populations of red blood cells and patchy skin pigmentation.

The chimaera is female and has two children. Her blood contains 99% group O, type AcP:BA, Pep-A:8-2 and 1% group A2B, type AcP:RA, Pep-A:1 red cells. H-, A- and B-transferase activities were demonstrated in her serum. The level of the H enzyme activity is low but is at the lower end of the normal range for group O persons. The levels of the A and B enzymes are also low but are higher than expected in a person with 1% A2B red cells in the blood. The levels of the A and B enzymes indicate that tissues other than the chimaera's haemopoietic tissue carry her genetically A2B cell line and are contributing the corresponding transferases to her plasma. Gross patchy skin pigmentation is present on the upper part of her body. The chimaera has evidently inherited two dissimilar germ nuclei from each parent.

Blood Group Antigens↗
PubMed1988

Increasing patient participation using an extended consultation: an inner city study.

An inner city practice in Birmingham has developed a new style of extended consultation to increase patient participation in primary care, based on previous initiatives in the practice, in particular allowing patients access to medical records, adopting an open reception style, and including consultations with a nurse practitioner. In a three stage consultation lasting approximately 30 minutes patients were offered a session with a receptionist for assisted access to medical records, a session of 15-20 minutes with a doctor or nurse and a self help session with a receptionist. This extended consultation was welcomed by patients, who showed a marked degree of participation, and it also increased the satisfaction and cooperation of project staff. This type of consultation provides a model for increasing patient participation in general practice.

Appointments and Schedules↗
PubMed1987

Coincident start sites for divergent transcripts at a randomly selected CpG-rich island of mouse.

We determined the nucleotide sequence of two HTF islands that were selected at random from mouse chromosomal DNA. Both were non-methylated, G + C rich, and contained CpG at close to the expected frequency. When used as probes, the two islands detected multiple transcripts in RNA from several mouse tissues. Cloned cDNAs for the major transcripts of one island (HTF9) were isolated and used to construct a transcriptional map. We found that HTF9 contains the origin of a pair of divergent transcripts that are probably messenger RNAs. The bidirectional promoter is different from those previously observed as the major transcription start sites for each orientation are coincident on opposite strands of the DNA. The results support the view that HTF islands often mark genes, and they suggest that bidirectional transcription may be a common feature of island promoters.

Amino Acid Sequence↗
PubMed1987

Tumor necrosis factor-alpha and hematopoietic progenitors: effects of tumor necrosis factor on the growth of erythroid progenitors CFU-E and BFU-E and the hematopoietic cell lines K562, HL60, and HEL cells.

Macrophages can modulate the growth of hematopoietic progenitors. We have examined the effects of tumor necrosis factor-alpha, a product of activated macrophages, on human erythroid progenitors (CFU-E, BFU-E) and the hematopoietic cell lines K562, HL60, and HEL cells. Tumor necrosis factor (TNF) significantly inhibited CFU-E and BFU-E growth at concentrations as low as 10(-11)-10(-12) M (0.2 U/ml), although erythroid colony and burst formation were not totally ablated. Preincubation of marrow samples with TNF for 15 min was sufficient to suppress erythroid colony and burst formation. Addition of TNF after the start of culture inhibited CFU-E- and BFU-E-derived colony formation if TNF was added within the first 48 h of culture. Additionally, TNF inhibited the growth of highly purified erythroid progenitors harvested from day 5 BFU-E. The colonies which formed in cultures treated with TNF were significantly smaller than those formed in control cultures. TNF (10(-8)-10(-10) M) also suppressed the growth of the hematopoietic cell lines K562, HL60, and HEL cells, with 40%-60% of the cells being sensitive to TNF. Preincubation of HL60 cells with TNF for 15 min significantly inhibited their growth. K562, HL60, and HEL cells expressed high-affinity receptors for TNF in low numbers (6000-10,000 receptors per cell). Fluorescence-activated cell sorter analysis of TNF binding to HEL cells demonstrated that the majority of these cells expressed TNF receptors. These data suggest that: (1) TNF is a rapid irreversible and extremely potent inhibitor of CFU-E, BFU-E, and hematopoietic cell lines K562, HL60, and HEL cells; (2) TNF appears to be acting on a subpopulation of erythroid cells, predominantly CFU-E, BFU-E, and possibly proerythroblasts; (3) TNF appears not to require accessory cells such as lymphocytes or macrophages to inhibit erythroid progenitors; and (4) the presence of TNF receptors on hematopoietic cells is not sufficient to confer sensitivity to TNF since the majority (80%-95%) of HEL cells express TNF receptors while only 40%-60% are inhibited by TNF.

Cell Differentiation↗
PubMed1986

Association of the human Lewis blood group Le(a-b-c-d-) with the failure of expression of alpha-3-L fucosyltransferase.

Two unrelated individuals are reported who lack alpha-3-L-fucosyltransferase activity in their serum and saliva. Both were blacks, one from the United States and the other from South Africa. No other of the tested members of their families lacked this enzyme. A survey of more than 2000 serum samples from both black and white South African blood donors, black United States donors and white United Kingdom donors failed to disclose another example of a serum deficient in alpha-3-L-fucosyltransferase activity. The two individuals lacking in alpha-3-L-fucosyltransferase activity both had the Lewis blood group phenotype Le(a-b-c-d-). No other persons with this phenotype have been reported. The absence of Lec activity in the two individuals who are deficient in alpha-3-L-fucosyltransferase is consistent with the interpretation that alpha-3-linked L-fucose is an essential part of the antigenic determinant recognised by the anti-Lec reagent used in this investigation.

Black People↗