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Biomedical subjects

D A James

Publications and source records attributed to D A James.

At least 19 recordsLinked to original sources

Internet based ECG medical information system.

Physiological monitoring of humans for medical applications is well established and ready to be adapted to the Internet. This paper describes the implementation of a Medical Information System (MIS-ECG system) incorporating an Internet based ECG acquisition device. Traditionally clinical monitoring of ECG is largely a labour intensive process with data being typically stored on paper. Until recently, ECG monitoring applications have also been constrained somewhat by the size of the equipment required. Today's technology enables large and fixed hospital monitoring systems to be replaced by small portable devices. With an increasing emphasis on health management a truly integrated information system for the acquisition, analysis, patient particulars and archiving is now a realistic possibility. This paper describes recent Internet and technological advances and presents the design and testing of the MIS-ECG system that utilises those advances.

Database Management Systems↗

Kinetic characterization of ribonuclease S mutants containing photoisomerizable phenylazophenylalanine residues.

Incorporation of the photoisomerizable amino acid phenylazophenylalanine (PAP) into enzyme structures has been proposed as a strategy for photoswitching enzyme activity. To evaluate the strengths and limitations of this approach to enzyme photo-control, we performed a kinetic analysis of RNase S analogues containing PAP in positions 4, 7, 8, 10, 11 or 13. For an enzyme containing a single PAP group, the maximum extent of photoconversion (between approximately 96% trans/4% cis and 10% trans/90% cis under standard conditions) sets a limit on the maximum fold change in the initial rate of approximately 25-fold, if the cis form is the more active isomer, and approximately 10-fold if the trans form is more active. This extent of photoswitching was not realized in the present case because the effects of photoisomerization on kinetic constants were small and distributed among effects on S-peptide binding, substrate binding and the rate of the chemical step. These results suggest that photoisomerization could substantially alter enzyme kinetic constants but that a directed combinatorial approach might be required for realizing maximal photo-control in such systems. The limit set by the extent of photoconversion might be overcome by coupling multiple PAP groups to one enzyme or by altering the behaviour of a system that required oligomerization for activity.

Amino Acid Sequence↗

Self-assembly of oligomeric porphyrin rings.

A cobalt porphyrin equipped with two different but geometrically complementary pyridine ligands self-assembles to form an unusually stable complex with approximately 12 porphyrin monomers arranged in a macrocyclic array.

Cobalt↗

Synthesis and estrogen receptor binding affinity of a porphyrin-estradiol conjugate for targeted photodynamic therapy of cancer.

A tetraphenylporphyrin-C11-beta-estradiol conjugate has been synthesized. Competitive binding assay of the conjugate with estrogen receptor (ER)-ligand-binding domain showed that the conjugate binds specifically to the protein with high affinity. Potential use of this conjugate to selectively deliver cytotoxic porphyrins to ER-positive cells in various carcinomas is discussed.

Animals↗

An anion-selective analogue of the channel-forming peptide alamethicin.

The peptide alamethicin self-assembles to form helix bundle ion channels in membranes. Previous macroscopic measurements have shown that these channels are mildly cation-selective. Models indicate that a source of cation selectivity is a zone of partial negative charge toward the C-terminal end of the peptide. We synthesized an alamethicin derivative with a lysine in this zone (replacing the glutamine at position 18 in the sequence). Microscopic (single-channel) measurements demonstrate that dimeric alamethicin-lysine18 (alm-K18) forms mildly anion-selective channels under conditions where channels formed by the parent peptide are cation-selective. Long-range electrostatic interactions can explain the inversion of ion selectivity and the conductance properties of alamethicin channels.

Alamethicin↗

Engineering charge selectivity in alamethicin channels.

The peptide alamethicin provides a system for engineering ion channel charge selectivity. To define alamethicin charge selectivity experimentally, we measured single-channel current-voltage relationships in KCl gradients using covalently linked peptide dimers. Two factors were found to contribute to the charge selectivity of these channels: (i) the ionic strength of the surrounding solutions; and (ii) the distribution of fixed charge on the peptide. Native alamethicin channels exhibited either cation selectivity or anion selectivity depending on which end of the channel was at the low salt side of the membrane. When the glutamine residue at position 18 in the sequence was replaced with a lysine residue, an anion-selective channel was obtained regardless of which end of the channel was at the low salt side of the membrane.

Alamethicin↗

Identifying and reducing noise in psychophysiological recordings.

Psychophysiology continues to be a widely used methodology in the study of human behaviour, emotion and cognition. The new researcher is faced with a number of problems in the recording process since the desired physiological signal must be isolated from a variety of noise sources. Precautions and strategies that can be implemented in setting up the recording equipment and isolating the subject from interference are described. There are also a number of software techniques that can be applied to improve signal quality after the data have been acquired. An overview is provided of hardware and software methods used to maximise the signal quality.

Artifacts↗

PATIC: a conformationally constrained photoisomerizable amino acid.

The synthesis of a conformationally constrained photoisomerizable amino acid, phenylazo-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid (PATIC), is described. This amino acid can be incorporated into peptides using standard Fmoc procedures and can be accommodated within alpha-helical structures albeit with some loss of stability of the structure. PATIC can serve as a useful building block for the synthesis of photoregulated peptides and proteins.

Azo Compounds↗

A fluorescence-based assay for ribonuclease A activity.

A sensitive assay for ribonuclease A activity based on the relief of fluorescence quenching within a defined oligomeric substrate (5' fluorescein-AAAArUAAAA-3'-rhodamine) is described. The substrate can be produced using an automated nucleic acid synthesizer and commercially available reagents. Together with a nonfluorescent cosubstrate (5'-dimethoxytrityl-AAAArUAAAA), the compound can be used to determine kinetic constants for the first step (transphosphorylation) of the ribonuclease-catalyzed reaction. These measurements should be useful for structure-based analyses of ribonuclease activity since a crystal structure has been determined for a closely analogous enzyme-inhibitor complex.

Fluoresceins↗

Potency and selective toxicity of tetra(hydroxyphenyl)- and tetrakis(dihydroxyphenyl)porphyrins in human melanoma cells, with and without exposure to red light.

A series of tetra(hydroxyphenyl)-(2-, 3- and 4-hydroxy; THPP) and tetrakis(dihydroxyphenyl)porphyrins (2,3-, 2,4-, 2,5-, 3,4-, and 3.5-dihydroxy; TDHPP) was synthesized and tested for toxicity in HeLa cells and human melanoma cell lines. Irradiation of drug-treated cells with > 600 nm light greatly increased the toxicity of all drugs except the 2,5- and 3,5-TDHPP. The THPP were more toxic than TDHPP in all cell lines, with or without irradiation; of the dihydroxy derivatives, the 3,4- and 2,4-isomers were the most toxic and the 2,5-isomer was the least toxic. The MM96E melanoma cell line, shown previously to be sensitive to hydrogen peroxide and superoxide ion, was not hypersensitive to killing by any of the above agents. HeLa cells, which lacked glutathione-S-transferase activity, were sensitive to the 4- and 2,3-isomers after irradiation; similar amounts of all drugs were taken up by HeLa cells. The pigmented melanoma cell line MM418, resistant to UV-B and in situ-generated hydrogen peroxide but sensitive to glutathione (GSH) depletion, was found to be resistant to the 2,3-isomer (no irradiation) and sensitive to the 3,4-isomer. The results indicate that (1) phototoxicity in these phenylporphyrins is not mediated by superoxide ions or hydroxyl radicals, (2) toxicity is dependent on the orientation of the hydroxy groups, (3) GSH transferase and possibly GSH itself offer protection from the 4- and 3,4-derivatives, respectively, and (4) the 3,4-derivative and analogues of similar selectivity should be evaluated further for the treatment of primary melanoma.

HeLa Cells↗

HIV roundtable. Strategies to enhance professional awareness and involvement. Part II.

Despite extensive public attention to the social and medical problems associated with HIV infection and AIDS, many clinicians remain largely uninvolved in public health and patient counseling programs aimed at preventing infection and getting patients into treatment. Suggestions to enhance professional involvement include improved schooling and continuing medical education; increased liaison and exchange of information among the various groups working with AIDS patients and at-risk populations; and programs to help clinicians confront their own feelings and concerns relating to AIDS.

Community-Institutional Relations↗

HIV roundtable. Strategies to enhance professional awareness and involvement, Part I.

Despite extensive public attention to the social and medical problems associated with HIV infection and AIDS, many clinicians remain largely uninvolved in public health and patient counseling programs aimed at preventing infection and getting patients into treatment. Suggestions to enhance professional involvement include improved schooling and continuing medical education; increased liaison and exchange of information among the various groups working with AIDS patients and at-risk populations; and programs to help clinicians confront their own feelings and concerns relating to AIDS.

Acquired Immunodeficiency Syndrome↗

PAs and HIV-antibody testing. The need for guidelines when the practitioner is at risk. Discussion.

The PA profession should establish guidelines for PAs at risk for infection with the human immunodeficiency virus (HIV) who wish to be tested for HIV antibody. Confidentiality and anonymity are critical factors, along with the employer's established policies. PAs working in emergency and surgical settings may be at greater professional risk of exposure to HIV; those with personal risk factors may consider being tested if their work exposes them to opportunistic infections. A clearinghouse for information should be established through the American Academy of Physician Assistants and state chapters.

Acquired Immunodeficiency Syndrome↗

PA impairment due to HIV infection. Part II: Building a professional support network. Forum.

Several members of the AAPA's Lesbian and Gay Physician Assistants Caucus who participated in the roundtable PAs and HIV-Antibody Testing: The Need for Guidelines When the Practitioner Is at Risk (1989;13[5]:146-158) met with members of the 12-Step/Caduceus Caucus to begin developing a cooperative effort to assist PAs who test positive for antibodies to the human immunodeficiency virus, and to explore other HIV-associated impairment issues. Part II focuses on concerns of the provider who is HIV-antibody positive as well as ways PA groups can cooperate to raise the profession's conciousness further and recommend guidelines and policy.

HIV Infections↗

A comparison of alternative distributions of postimplantation death in the dominant lethal assay.

Statistical analysis of dominant lethal assay data has been the subject of much discussion, a large part of which has been concerned with the distributional form displayed by postimplantation embryonic deaths. The purpose of this study was to compare the fit of the frequently suggested distributions and some others, and to comment on the effect of distribution upon interpretation of results, using a particular set of dominant lethal assay data. The data set used included experiments involving a known mutagen (cyclophosphamide). For these experiments the parameters of the best fitting distributions were reviewed to consider how a dominant lethal effect is displayed.

Animals↗

The experimental treatment of two cases of auditory hallucinations.

Two cases are described where auditory hallucinations persisted, in spite of medication, in two schizophrenic patients, one with acute onset and one with a severe chronic illness. The hallucinations were treated successfully by methods derived from Green's theory that auditory hallucinations are represented in the non-dominant hemisphere.

Adult↗

Toxicity testing of atracurium.

The toxicity of atracurium has been investigated in subacute tests in rat, dog and monkey, in a fetal toxicity test in the rabbit and in a paranatal study in the cat. No specific adverse effects were found despite administration of supraparalysing doses. It appeared not to cross the placenta at term and the neonatal kitten seemed resistant to its neuromuscular blocking action. In the dog, cat and pig, in which physiological monitoring was undertaken, i.v. injection of three to four times the paralysing dose had little or no effect on arterial pressure or heart rate. The solution did not cause local irritation. Atracurium was not mutagenic in the Ames test.

Animals↗

Analysis of results from a collaborative study of the dominant lethal assay.

A dominant lethal (DL) mutation is a genetic change that results in the death of the conceptus that inherits it. The assay is normally carried out in mice and the production of DL mutation by the test chemical is characterised by an increase in non-viable embryos. A distinct advantage of the DL assay is that it is an in vivo, mammalian, germ cell assay and is therefore pertinent to the fundamental question of chemical mutagenesis, i.e.: is a chemical likely to produce genetic changes that can be transferred to the offspring? The two principal criticisms of the assay are that the main type of genetic damage it detects is chromosomal breakage that leads to death of the conceptus, and that the assay is considered to be relatively insensitive. The Association of the British Pharmaceutical Industry (ABPI) Working Party on Mutagenicity was established in 1974. Its principal objective was to consider the problem of mutagenicity and associated matters in relation to the development of new medicines and to make recommendations and proposals for collaborative work if indicated. The dominant lethal assay is one of several tests for mutagenicity chosen for evaluation by collaborative study. The objective of the collaborative study was to gain more information about the validity and dependability of the dominant lethal assay. The present report concerns an analysis of the differences between compounds, laboratories and statistical methods utilising the data from the collaborative study.

Animals↗