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Biomedical subjects

D J Baker

Publications and source records attributed to D J Baker.

At least 19 recordsLinked to original sources
PubMed1995

Marketed sperm: use and regulation in the United States.

OBJECTIVE: To collate information relating to the current use of marketed semen for therapeutic donor insemination (DI) in the United States. DATA IDENTIFICATION: Literature was identified by Medline search and government document review. LITERATURE SELECTION: Materials selected for review included empirical studies, policy reviews, legal documents, and government surveys relating to use of donor sperm. RESULTS: Use of marketed (donor) sperm is associated with significant medical, genetic, and psychological risk. These risks directly affect the individuals involved in therapeutic DI. Also, the public's health is involved because these risks include transmission of infectious disease and genetic anomalies. Legal and social concerns associated with therapeutic DI include offspring's knowledge of genetic endowment, parental responsibility, and donor confidentiality. This analysis shows that policies currently in place regarding the use of marketed semen in therapeutic DI do not ensure consumer safety and do not protect society's interest. CONCLUSIONS: Current policies need to be improved to protect those directly involved in the therapeutic DI process and to address public health and societal concerns. Recommendations include: [1] programs to assure quality and safety of marketed sperm, [2] implementation of a central registry to collect information about the use and outcomes of therapeutic DI, and [3H] expansion of available therapeutic DI guidelines to address psychological and social support for persons involved in therapeutic DI.

Commerce↗
PubMed1994

The response of M.HpaII to heteroduplexes.

Synthetic oligodeoxyribonucleotide duplexes have been used to study the methylation specificity of M.HpaII, a bacterial DNA methyltransferase. Substrates of four types were compared. A 30-mer containing a Watson-Crick paired CCGG recognition sequence was rapidly methylated at the central cytosine on each strand in the recognition sequence. A 30-mer containing an asymmetrically methylated recognition sequence, of the type transiently produced by DNA replication, was rapidly methylated at the central cytosine on the unmethylated strand. A heteroduplex containing an A.C mispair in the recognition sequence (CCGG/CCAG) was rapidly methylated at the cytosine in the mispair. A heteroduplex containing an A.C and an adjacent C.C mispair in the recognition sequence (CCGG/CCCA) was not methylated at a significant rate. The results show that M.HpaII can tolerate a single mispair at its recognition site in a heteroduplex without loss of activity or specificity.

DNA-Cytosine Methylases↗
PubMed1994

Hypermethylation of telomere-like foldbacks at codon 12 of the human c-Ha-ras gene and the trinucleotide repeat of the FMR-1 gene of fragile X.

Runs of G residues on the G-rich strands of 30mers from the region spanning codon 12 of c-Ha-ras appear to be protected against chemical modification by dimethylsulfate. This suggests that the G-rich strand might spontaneously form a Hoogsteen-paired quadruplex, which is characteristic of telomere-like DNA sequences. In this report we show that the predominant species in 1:1 mixtures of complementary 30mers from this region are duplex DNA and a smaller amount of unimolecular foldback formed by the C-rich strand. Foldbacks of this type resemble structures first observed in the C-rich strand of telomeric DNA and also occur at the CCG triplet repeat present in the FMR-1 gene of human fragile X syndrome. Foldbacks from the C-rich strand of c-Ha-ras and the FMR-1 triplet repeat are exceptional substrates for the human methyltransferase in isolation. Substituting inosine for guanosine alters the secondary structure of the folded oligomers and dramatically reduces their ability to serve as substrates for the human methyltransferase, suggesting that secondary structure is required for recognition by the enzyme. These findings suggest that one mechanism by which methyl groups accumulate in the c-Ha-ras region of chromosome 11 during carcinogenesis and at the FMR-1 locus during repeat expansion at fragile X may be structurally induced de novo methylation at sites undergoing local conformational change. Such methylation might serve to mark unusual structures for repair. In the absence of repair, asymmetrically methylated duplexes produced by resolution of the unusual structures would be rapidly converted to symmetrically methylated duplexes through the methyl-directed activity also carried by the human methyltransferase.

Base Sequence↗
PubMed1992

Immunogenicity of inactivated influenza vaccine in residential homes for elderly people.

One hundred and seventy residents of 11 Leicester City Council homes for the elderly, with a total of 515 beds, were studied during a 30-week period from September 1988 to March 1989 to determine the use of influenza vaccine, the levels of influenza antibody, the incidence of influenza, and the protection afforded by vaccination. The study group of 133 women and 37 men had a mean age of 85 years and 59% had one or more chronic medical conditions. The immunization rates by home for the 170 symptomatic residents ranged from 8% to 90% (mean 45%). Seventy-one sera, 36 from vaccinated and 35 from non-vaccinated residents were collected between 1 December 1988 and 24 March 1989 and were assayed for antibody to A/Taiwan/1/86 (H1N1), A Sichuan/2/87 (H3N2) and B/Beijing/1/87. Analysis revealed no statistically significant differences between the antibody profiles of vaccinated and unvaccinated subjects. Six influenza A and 6 influenza B infections were confirmed among the 170 subjects with upper respiratory tract infections. Influenza vaccination was not associated with significant levels of protection against influenza A or B. Studies of the haemagglutinins of the vaccine strains and influenza isolates during 1988/89 showed that they were closely related.

Aged↗
PubMed1992

Localization of c-fos-like proteins in the mouse endometrium during the peri-implantation period.

Fos, which collectively refers to protein products of the c-fos proto-oncogene family, was immunohistochemically localized in the mouse uterus to ascertain the effects of steroids on Fos expression in the mouse and to determine the course of Fos expression during normal pregnancy and pseudopregnancy. In ovariectomized mice, Fos was induced in luminal and glandular epithelium and an occasional stromal cell following treatment with 100 ng 17 beta-estradiol (E2). Priming with 2 mg progesterone (P4) for 3 days prior to the administration of 100 ng E2 or giving 100 ng E2 and 2 mg P4 concomitantly induced Fos in the luminal and glandular epithelium with enhanced staining in stromal cells. Priming with P4 before giving E2 had the added effect of inducing Fos at an earlier time point. Progesterone alone failed to induce Fos in any cell type in the uteri of ovariectomized animals. On Days 1 and 2 of pregnancy and pseudopregnancy, Fos was detected in the luminal and glandular epithelium and in the stroma. Staining was decreased by Day 3 and was not detectable by the morning of Day 4. No further staining for Fos was found during subsequent days of pseudopregnancy. On the afternoon of Day 4 of pregnancy, Fos was detected in the epithelium and the antimesometrial stroma. On the morning of Day 5, implantation sites and non-site areas were distinguishable, with Fos present in luminal epithelium and antimesometrial stroma in sites, and in just the luminal epithelium in non-sites. Fos remained in the epithelium of non-sites through Day 7 of pregnancy. In sites on the afternoon of Day 5, staining was found in the luminal epithelium and primary decidual zone. On Day 6, staining was found in the secondary decidual zone, but was absent from the primary zone and epithelium. On Day 7, Fos was also detected in the embryonic trophoblast giant cells and the ectoplacental cone. These results demonstrate that E2 and P4 modulate Fos in the mouse endometrium and that Fos is induced during implantation. Significantly, the embryo appears to induce Fos expression on the afternoon of Day 4, while it is still encased in the zona pellucida.

Amino Acid Sequence↗
PubMed1991

Recognition of unusual DNA structures by human DNA (cytosine-5)methyltransferase.

The symmetry of the responses of the human DNA (cytosine-5)methyltransferase to alternative placements of 5-methylcytosine in model oligodeoxynucleotide duplexes containing unusual structures has been examined. The results of these experiments more clearly define the DNA recognition specificity of the enzyme. A simple three-nucleotide recognition motif within the CG dinucleotide pair can be identified in each enzymatically methylated duplex. The data can be summarized by numbering the four nucleotides in the dinucleotide pair thus: 1 4/2 3. With reference to this numbering scheme, position 1 can be occupied by cytosine or 5-methylcytosine; position 2 can be occupied by guanosine or inosine; position 3, the site of enzymatic methylation, can be occupied only by cytosine; and position 4 can be occupied by guanosine, inosine, O6-methylguanosine, cytosine, adenosine, an abasic site, or the 3' hydroxyl group at the end of a gapped molecule. Replacing the guanosine normally found at position 4 with any of the moieties introduces unusual (non-Watson-Crick) pairing at position 3 and generally enhances methylation of the cytosine at that site. The exceptional facility of the enzyme in actively methylating unusual DNA structures suggests that the evolution of the DNA methyltransferase, and perhaps DNA methylation itself, may be linked to the biological occurrence of unusual DNA structures.

5-Methylcytosine↗
PubMed1991

Effect of pretreatment with oral pyridostigmine on subsequent activity of alcuronium in non-anaesthetized subjects.

We have studied the effects of alcuronium in 10 healthy, non-anaesthetized volunteers after they had been taking oral pyridostigmine 30 mg 8 hourly. The responses of adductor pollicis were recorded using an isolated forearm procedure (IFP) during onset and recovery of neuromuscular block produced by 1.5 mg of relaxant. Previously noted disparities between mechanomyogram and electromyogram measurement of the first response of the train-of-four (T1) and the ratio of the fourth (T4) to the first response (TOF ratio) were found in most cases, but were unaffected by pyridostigmine. Pyridostigmine did not affect significantly the overall characteristics of neuromuscular block, but repeated IFP after a placebo unexpectedly produced marginally less depression of T1 and more rapid recovery. The hysteresis relationship between T1 and T4 during onset and recovery of block was confirmed, but was not affected by pyridostigmine. Clinically, the results may indicate that pyridostigmine pretreatment is unlikely to have significant effects on the subsequent use of alcuronium.

Administration, Oral↗
PubMed1991

Effect of calcium channel blocking agents on infarct size after ischaemia-reperfusion in anaesthetised pigs: relationship between cardioprotection and cardiodepression.

We compared the abilities of verapamil and nicardipine to protect the porcine myocardium from the consequences of ischaemia-reperfusion in vivo. Infusion of verapamil (50 micrograms/kg) into the left anterior descending coronary artery LAD (i.c.a.), in 15 min immediately before ligation depressed regional contractile function, reduced infarct size by 80%, and enabled contractile function to recover partially during reperfusion. Verapamil (10 micrograms/kg i.c.a.) did not depress contractile function before ligation or permit its recovery during reperfusion, despite reducing infarct size by 80%. Lower doses of verapamil were not cardioprotective. Nicardipine (10 and 30 micrograms/kg i.c.a.) depressed contractile function before ligation but did not permit its recovery during reperfusion. Nicardipine did not reduce infarct size development. Thus, drug-induced negative inotropic activity (which presumably reflects myocardial calcium channel blockade) and cardioprotection are not linked. Verapamil can markedly reduce infarct size development at a dose that exerts no detectable negative inotropic activity. This cardioprotective effect of verapamil was greatly reduced by intravenous (i.v) pretreatment with aspirin (30 mg/kg), which alone did not alter infarct size development. Thus, the cardioprotective effect of verapamil (10 micrograms/kg i.c.a.) appears to be mediated by a cyclooxygenase product, possibly prostacyclin.

Animals↗
PubMed1990

Acute upper respiratory tract viral illness and influenza immunization in homes for the elderly.

Occupants of 482 long-stay and 33 short-stay beds in 11 Leicester City Council homes for the elderly were studied during a 30-week period from September 1988 to March 1989 to determine the incidence, aetiology, morbidity, and mortality of acute upper respiratory tract viral infections and the use of influenza vaccine. Influenza immunization rates by home ranged from 15.4 to 90% (mean 45%). There were no differences in the distribution of medical conditions by home. The highest immunization rates were seen in people with chest disease (77%), heart disease (60%), diabetes (56%), and those with three medical conditions (75%). There was an average of 0.7 upper respiratory episodes per bed per annum with a mortality of 3.4% (6/179). Half of all episodes were seen by a general medical practitioner and 81 of 90 (90%) referrals were prescribed antibiotics costing approximately 7.50 pounds per patient. Lower respiratory tract complications developed during 45 (25%) of 179 episodes including 3 of 12 coronavirus infections, 3 of 9 respiratory syncytial virus infections, 2 of 4 adenovirus infections, 1 of 11 rhinovirus infections, but none of 5 influenza infections. Respiratory infections were caused mostly by pathogens other than influenza virus during the influenza period documented nationally. This highlights the role of coronaviruses, respiratory syncytial virus, and unidentified agents in the elderly, and questions the assumptions made in American estimates on the impact of influenza and the value of influenza vaccines.

Acute Disease↗
PubMed1990

Interferon activity is not detected in blastocyst secretions and does not induce decidualization in mice.

Mouse trophoblast cells synthesized and secreted proteins during the peri-implantation period, some in the molecular size range of alpha interferons (IFN-alpha), known mediators of the maternal recognition of pregnancy in sheep and cows. However, conditioned media samples containing secreted proteins from Day-5 mouse blastocysts or from trophoblast outgrowths did not contain detectable levels of antiviral activity indicative of IFN. In addition, it was not possible to induce a decidual reaction in suitably sensitized uteri with intraluminal instillation of IFN-alpha. The results indicate that IFNs are probably not involved in the maternal recognition of pregnancy at the time of implantation in the mouse.

Animals↗
PubMed1989

A G4-DNA/B-DNA junction at codon 12 of c-Ha-ras is actively and asymmetrically methylated by DNA(cytosine-5)methyltransferase.

Oligodeoxynucleotides spanning codon 12 of the human c-Ha-ras gene were found to be exceptionally good substrates for de novo methylation by human DNA(cytosine-5)methyltransferase. In the complex formed by two complementary 30mers, only the C-rich strand was methylated by the enzyme. Guanines at the 3' end of the G-rich strand of the complex could not be completely modified by dimethyl sulfate [corrected] suggesting tetrameric bonding at these G-residues. An eight-stranded structure, composed of four duplex DNAs at one end, joined to a G4-DNA segment at the other with the junction between the two DNA forms at codon 12, can account for our results.

Base Sequence↗
PubMed1989

Train-of-four fade during onset and recovery of neuromuscular block: a study in non-anaesthetized subjects.

The actions of alcuronium, vecuronium and tubocurarine have been studied in the isolated forearms of six healthy, non-anaesthetized volunteers. The responses of adductor pollicis were measured during onset and recovery of neuromuscular block for each agent. There was a drug-related disparity between mechanomyogram (MMG) and electromyogram (EMG) measurement of the first response of the train-of-four (T1) and of the ratio of the fourth (T4) to the first response (TOF ratio). There were significantly higher T1 values for the EMG than for MMG during alcuronium blockade (P = 0.03). For tubocurarine, however, the relationship was reversed. The relationship between T1 and TOF ratio during onset and recovery of neuromuscular block was a hysteresis. The TOF ratio at 50% T1 was significantly higher during onset than during recovery for all three drugs, measured by MMG or EMG (P less than 0.005). Analysis of variance of the differential fade loops failed to show a drug-related effect. We conclude that care should be taken in assuming interchangeability between MMG and EMG measurement of T1. Relationships between T1 and TOF ratio derived during recovery do not necessarily apply during onset and may lead to error in estimating the degree of muscle relaxation.

Alcuronium↗
PubMed1989

A computer-based interview system for patients with back pain. A validation study.

A microcomputer-based system has been designed to interview patients with a view to investigating and establishing common syndromes of back and leg pain. In a randomized crossover validation study, 50 consecutive outpatients were interviewed by the computer and had a conventional clerking by a doctor. The conventional clerking made minor errors in 3.75% of questions answered and major errors in 0.90%. The computer made minor errors in 6.75% of questions and major errors in 5.45%. The majority of the computer errors were due to inadequate question design. These have been corrected, and it is anticipated that the computer will now have an overall rate of 94% correct answers and be sufficiently accurate to pursue the aim of clinical syndrome identification.

Back Pain↗
PubMed1988

RglB facilitated cloning of highly methylated eukaryotic DNA: the human L1 transposon, plant DNA, and DNA methylated in vitro with human DNA methyltransferase.

In vitro methylation of Bluescribe plasmid DNA (pBS) with human placental DNA methyltransferase to 6% 5-methylcytosine (mC) reduced transformation efficiencies in rglB+ host strains C600 and DS410 by almost 2 orders of magnitude. By contrast, the rglB- derivative of DS410 showed no reduction in transformation efficiency with methylation while the rglB- derivative of C600 was partially tolerant to methylation. Further, we show that the 1.8 kilobase (kb) and 1.2 kb KpnI fragments derived from the human L1 repeat have respectively 18.3% and 2.3% mC in vivo. Using these hyper- and hypo-methylated genomic segments ligated into the pBS plasmid, transformants with the highly methylated 1.8 kb L1 insert were recovered at 17 to 40 fold higher frequency with the rglB- host strains than with the rglB+ hosts. In addition, recombinant phage (lambda 2001) containing inserts of plant genomic DNA with 26.7% mC (from Petunia hybrida) when plated on rglB- hosts gave titres up to 222 times higher than on the rglB+ strains.

Cell Line↗
PubMed1987

Human DNA (cytosine-5)methyltransferase selectively methylates duplex DNA containing mispairs.

The presence of the C.C mispair in a defined duplex oligodeoxynucleotide enhanced its capacity to serve as a substrate for highly purified human DNA methyltransferase. Analysis of tritiated reaction products showed that the C.C mispair acted as a "methylation acceptor" in that it was itself rapidly methylated. The m5C.G base pair also enhanced the capacity of the oligodeoxynucleotide to serve as a substrate for the enzyme. However, this complementary base pair was found to act as a "methylation director". That is, the presence of the m5C in one strand induced the enzyme to rapidly methylate at the cytosine residue on the opposite strand in an adjacent C.G base pair.

Base Composition↗