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Biomedical subjects

H Walton

Publications and source records attributed to H Walton.

At least 19 recordsLinked to original sources
PubMed1998

Effect of arsenite on induction of CYP1A and CYP2H in primary cultures of chick hepatocytes.

In earlier studies, treatment with sodium arsenite was shown to decrease total hepatic CYP in rats. A concomitant increase in heme oxygenase, the rate-limiting step in heme degradation to biliverdin, was considered responsible for the decrease in CYP. Here we investigated the effect of sodium arsenite on induction of CYP2H, CYP1A, and heme oxygenase in primary cultures of chicken embryo hepatocytes. When added simultaneously with inducer, arsenite inhibited phenobarbital-mediated increases in CYP2H and 3-methylcholanthrene-mediated increases in CYP1A, as measured enzymatically and immunochemically. Near maximal decreases were observed in these forms of CYP at a concentration of 2.5 microM sodium arsenite. The concentration-dependent decreases in CYP2H and CYP1A by sodium arsenite were concomitant with increases in heme oxygenase. Sodium arsenite was not toxic at concentrations as high as 10 microM, as indicated by protein synthesis and the reduction of MTT by intact cells. Sodium arsenite had no effect on induction of CYP2H1 mRNA, suggesting that the decreases in this form of CYP occurred post-transcriptionally. Treatment of cells with tin mesoporphyrin (SnMeso), an inhibitor of heme oxygenase, resulted in inhibition of arsenite-induced heme oxygenase. However, SnMeso did not alter the effect of arsenite to prevent phenobarbital-mediated increases in CYP2H protein. SnMeso alone inhibited phenobarbital-mediated increases in CYP2H. Inclusion of 2 or 5 microM exogenous heme with arsenite did not prevent the arsenite-mediated decrease in CYP2H. Combined treatment with heme and phenobarbital induced heme oxygenase to the same extent as treatment with heme, arsenite, and phenobarbital. However, CYP2H activity was decreased only when the treatment included arsenite. These results suggest that elevated levels of heme oxygenase alone are not responsible for arsenite-mediated decreases in CYP2H.

Animals↗
PubMed1995

Opposing actions of angiotensin-(1-7) and angiotensin II in the brain of transgenic hypertensive rats.

Lack of specific antagonists to the amino-terminal heptapeptide angiotensin-(1-7) [Ang-(1-7)] prompted us to evaluate the central effects of delivering a specific affinity-purified Ang-(1-7) antibody on the blood pressure and heart rate of 12-week-old conscious homozygous female rats (n = 12) expressing the mouse submandibular Ren-2d gene [(mRen-2d)27] in their genome. Another group of transgenic hypertensive and strain-matched Sprague-Dawley controls were injected with a specific Ang II monoclonal antibody (KAA8). Cerebroventricular administration of the affinity-purified Ang-(1-7) antibody in conscious transgenic hypertensive rats caused significant dose-related elevations in blood pressure associated with tachycardia. The hypertensive response was augmented in transgenic rats studied 7 to 10 days after cessation of lisinopril therapy. Neutralization of Ang II with the Ang II antibody caused a hemodynamic response opposite to that obtained with the Ang-(1-7) antibody. All doses of the Ang II antibody produced hypotension and bradycardia. The magnitude of the depressor response was significantly augmented in transgenic rats weaned off lisinopril therapy. In contrast, central administration of either the Ang-(1-7) or Ang II antibodies had no effect on normotensive rats. Central injections of an affinity-purified IgG fraction were ineffective in both control and transgene-positive rats. These data suggest that in the brain of transgenic hypertensive rats, Ang-(1-7) opposes the action of Ang II on the central mechanism or mechanisms that contribute to the maintenance of this model of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed1994

Identification of a structural epitope by using a peptide library displayed on filamentous bacteriophage.

The screening of phage-displayed random peptide libraries has recently emerged as a powerful technique for probing Ab-Ag interactions. We have used this method to identify the epitope recognized by a mAb, CB5B10, raised against plasminogen activator inhibitor type-1 (PAI-1). Two phage libraries, displaying random hexapeptides with or without flanking cysteine residues, were screened for binding to mAb CB5B10. The selected phages were shown to contain similar peptide sequences, all of which were flanked by cysteines. When compared with the crystal structure of PAI-1, the selected peptides closely resemble the sequence of a solvent-exposed loop connecting the COOH-terminal of an alpha-helix at Phe114 to a beta-sheet at Ser119. Because of the constraints imposed by the flanking cysteine residues, the selected peptides appear to mimic the structure and the sequence of the PAI-1 epitope. Specific contacts between the amino acids displayed by the phage and the mAb were explored using site-directed mutants of the phage peptide. The effects of these substitutions on binding to the mAb correlated well with the accessibility of the corresponding residues in the PAI-1 epitope. This is the first example of the use of phage-displayed peptide libraries to identify a structural epitope.

Amino Acid Sequence↗
PubMed1994

The educational responsibilities of a National Academy of Medicine.

Academies of Medicine now should see their educational mission as concern with all stages of medical education in the nation. Traditionally, National Academies have tended to regard Postgraduate Training as their proper educational responsibility. Such limitation is no longer defensible, particularly because medical education is now accepted as a continuum and, moreover, is viewed as lifelong. Discontinuities between basic education, specialist training and continuing education are now considered detrimental, and have to be eliminated. The Medical School Curriculum must be required to equip future doctors with the self-learning skills now essential for specialist training. The longest and most critically important phase of training has unquestionably become continuing medical education. It is argued therefore that basic medical education, specialist training and continuing education have all to be concerns of National Academies. National Academies in Europe, inevitably, have come to have profound international obligations now that free movement of doctors is legally established in the European Community.

Academies and Institutes↗
PubMed1993

Medical specialization in Europe: the way forward. Promotion of educational quality.

The medical specialties are being intensively reconsidered in the countries of Europe. The important need is for promoting improvement of educational training programmes. Evaluation and improvement of specialist training programmes is the priority and not the setting up of qualifying examinations. The first necessity is to safeguard 20 years of evolution in postgraduate training. Support for the educational process is essential, to a much greater extent than occurs at present, if standards are to be improved and the confidence of the public is to be retained. The EC medical education system is the only existing international structure in medical education which is controlled by law, and is on that basis alone of the greatest interest.

Education, Medical↗
PubMed1993

Medical education worldwide. A global strategy for medical education: partners in reform.

The on rush of beneficial change which now flows in medical education has never been stronger since the start of this century. Such activity has not been seen since the era of Flexner. There can be no doubt that the world scene is now set for decisive, effective action. The many tributaries of the stream of reform converge this year at Edinburgh, to diverge again into six Regional Conferences during 1994 in Africa, the Americas, the Eastern Mediterranean, Europe, South-East Asia and the Western Pacific. The centres of activity and connection cited below do not in any way make up a comprehensive catalogue. Rather, each development and each reform is a link in a chain, a module with which the World Federation for Medical Education (WFME) has been implicated. Each name given, each title stated, is intended as a marker, a nexus. These are among the partners to be mobilized and brought together for the task.

Community Medicine↗
PubMed1992

Effects of diphenyl ether herbicides on porphyrin accumulation by cultured hepatocytes.

Several diphenyl ether herbicides, such as acifluorfen methyl, have been previously shown to cause large accumulations of the heme and chlorophyll precursor, protoporphyrin, in plants. Light-induced herbicidal damage is mediated by the photoactive porphyrin. Here we investigate whether diphenyl ether herbicides can affect porphyrin synthesis in rat and chick hepatocytes. In rat hepatocyte cultures, protoporphyrin, as well as coproporphyrin, accumulated after treatment with acifluorfen or acifluorfen methyl. Combination of acifluorfen methyl with an esterase inhibitor to prevent the conversion of acifluorfen methyl to acifluorfen resulted in a greater accumulation of porphyrins than caused by acifluorfen methyl or acifluorfen alone. In vitro enzyme studies of hepatic mitochondria isolated from rat and chick embryos demonstrated that protoporphyrinogen oxidase, the penultimate enzyme of heme biosynthesis, was inhibited by low concentrations of acifluorfen, nitrofen, or acifluorfen methyl with the latter being the most potent inhibitor. These findings indicate that diphenyl ether treatment can cause protoporphyrin accumulation in rat hepatocyte cultures and suggest that this accumulation was associated with the inhibition of protoporphyrinogen oxidase. In cultured chick embryo hepatocytes, treatment with acifluorfen methyl plus an esterase inhibitor caused massive accumulation of uroporphyrin rather than protoporphyrin or coproporphyrin. Specific isozymes of cytochrome P450 were also induced in chick embryo hepatocytes. These effects were not observed in the absence of an esterase inhibitor. These results suggest that diphenyl ether herbicides can cause uroporphyrin accumulation similar to that induced by other cytochrome P450-inducing chemicals such as polyhalogenated aromatic hydrocarbons in the chick hepatocyte system.

Animals↗
PubMed1989

Radiosensitization of human colorectal tumor cells by 4-nitro-5-sulfonatoimidazoles.

Misonidazole, a clinically-effective 2-nitroimidazole hypoxic cell radiation sensitizer, and 12 4-nitro-5-sulfonatoimidazoles were tested in cultured human SW1116 colorectal adenocarcinoma cells for radiosensitizing efficiency. Octanol-water partition coefficients and HPLC capacity factors were determined for all agents as measurements of lipophilicity, and an excellent correlation was found between the two measurements. Cytotoxicity, in vitro glutathione reactivity, and one-electron reduction potential were also determined for each compound to evaluate potential utility as macromolecularly transported radiosensitizers. Ten members of the set were found to be 40 to 300 times more radiotoxic than misonidazole, but no correlation was found between their radiosensitizing efficiencies and the chemical and physical parameters.

Adenocarcinoma↗
PubMed1986

Treatment of trigger points with microamperage transcutaneous electrical nerve stimulation (TENS)--(the Electro-Acuscope 80).

One-half of the students taking part in a double-blind study received a microamperage electrical stimulation of trigger points in the neck and shoulder region with the Electro-Acuscope 80. All the subjects were evaluated by digital palpatory physical examination for the presence of trigger points before each of their treatments. Results indicate that the subjects who received treatment had a higher change of trigger-point indicators compared to those receiving the placebo treatment. A two-tailed t-test indicated significant results (P less than 0.001). It appears that microamperage electrical stimulation is effective in the treatment of trigger points.

Adult↗