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Biomedical subjects

D M Walker

Publications and source records attributed to D M Walker.

At least 73 records · Page 4Linked to original sources
PubMed1993

Global myocardial ischemia protects the myocardium from subsequent regional ischemia.

Many investigators use in vitro models of global ischemia to examine the effects of preconditioning, often with recovery of contractile function as the end-point. Such models are relevant to myocardial protection during cardiac surgery. However, there is still debate as to whether preconditioning preserves ventricular contraction secondary to limitation of infarction or by a direct effect on stunning. Since infarct size is the original end-point against which protection by preconditioning is measured, our aims were, first, to validate global ischemic preconditioning by measuring infarct size after subsequent regional ischemia and, second, to correlate limitation of infarct size with mechanical function. After stabilization, seven isolated buffer perfused rabbit hearts were subjected to 5 minutes of global "no-flow" ischemia followed by 10 minutes of reperfusion ("global preconditioning"). Seven control hearts were allowed to stabilize for an additional 15 minutes at constant flow. Subsequently, regional ischemia was induced in both groups for 45 minutes followed by 2 hours of reperfusion. Left ventricular and coronary perfusion pressures were measured throughout. Myocardial infarct size was measured using triphenyltetrazolium staining and expressed as a percentage of the area at risk outlined with fluorescent microspheres. The ratio of infarct to risk zone was reduced from 47.6 +/- 7.3% in control hearts to 16.4 +/- 5.4% (p = 0.005) in preconditioned hearts, confirming the efficacy of global preconditioning. In addition, preconditioning led to a better preservation of systolic function, which correlated significantly with limitation of infarct size (r = 0.75, p = 0.002). Global preconditioning may account for the successful use of cross-clamp fibrillation during cardiac surgery.

Animals↗
PubMed1992

The clonal organization of the squamous epithelium of the tongue.

Knowledge of the kinetics and stem cell localization of the mouse lingual epithelium is largely based on studies using DNA labelling techniques. We have adopted a different approach, using histochemistry for the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD). We have deduced clone size and morphology from studies of patch size and distribution in mice heterozygous for G6PD deficiency and from the identification of clonal enzyme loss induced in normal mice by application of a mutagen. Lingual epithelium of female mice (CBA X GPDX) heterozygous for G6PD deficiency showed multiple clearly defined patches of strong or weak enzyme activity, corresponding in intensity to the strong staining uniformly present in the normal parental strain (CBA) or to the weak staining uniformly present in the G6PD deficient parental strain (GPDX). This pattern results from the random suppression of either the paternal or the maternal X chromosome in each cell early in embryonic development, and the subsequent inheritance of X inactivation in daughter cells, giving rise to phenotypic patches each composed of one or more clones. The patch borders intersected the base of the lingual epithelium at small indentations or at the apices of connective tissue papillae; the surface intersection in some cases bisected filiform papillae. Patch width measured in tissue sections at the mid rete ridge level, showed a clear mode close to 40 microns, corresponding very closely to the mode for rete ridge width (i.e. distance between connective tissue papillae). Further evidence for clonal organization was obtained by inducing mutations in the lingual epithelium of CBA mice by topical mutagen application. A few clearly defined patches of enzyme loss were found with a mean diameter of 36 microns. Their morphology was very similar to that of patches in the heterozygous animals. We interpret these patches as clones derived from stem cells with induced somatic G6PD mutations. We conclude that the mouse lingual epithelium is a stem cell epithelium composed of clonal units of about 40 microns diameter, based on the rete ridge structure and that both connective tissue papillae and filiform papillae occur at the junction of two or more epithelial clones.

Animals↗
PubMed1992

The origins of the human immunodeficiency viruses: an update.

In 1981 a new acquired immunodeficiency syndrome was first described. The disease has a 100% mortality rate and over 359,000 cases have been reported to the WHO from 162 countries. The WHO estimates that the cumulative global total of AIDS cases as of early 1991 is more than 1.5 million. The dental profession, in line with other health care professions, is involved with guiding rational efforts to stop transmission and with developing effective means of treatment and prevention. This paper reviews the nature of the virus, its possible origins, and the implications of such origins for treatment and prevention of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Increased production of tumour necrosis factor by peripheral blood leukocytes in patients with recurrent oral aphthous ulceration.

Much evidence suggests that recurrent oral aphthous ulceration (RAU) is an immunologically mediated disease. Tumour necrosis factor has multiple biologic properties, some of which may be relevant to the pathogenesis of RAU. This study has assessed its production by peripheral blood leukocytes from aphthous patients in active and remission phases of disease and from patients with nonaphthous ulceration (diseased controls). Each ulcer patient was studied in parallel with a matched healthy control volunteer. A bioassay against the standard mouse fibrosarcoma line, L929, was used to assess the levels of tumour necrosis factor-alpha (TNF). Significantly greater amounts of TNF were released from unstimulated monocyte-enriched and monocyte-depleted leukocyte fractions in active RAU compared with those from healthy control donors, suggesting that this cytokine may be associated with RAU.

Adolescent↗
PubMed1992

Salivary IgA antigliadin antibody as a marker for coeliac disease.

In recent years, serum antibodies to gliadin (AGA) have been reported to be useful markers of coeliac disease. IgA AGA have also been found in intestinal secretions and saliva in coeliac disease and may offer a convenient, non-invasive screening test. In order to test this hypothesis, salivary and serum AGA were measured in children with coeliac disease proved by biopsy and compared with several control groups. Measurement of salivary IgA AGA provided excellent discrimination between those children with coeliac disease and the control groups, and our study suggests that it may provide a rapid, non-invasive method of screening for this disease before intestinal biopsy.

Adolescent↗
PubMed1991

Factors contributing to chromosome damage in lymphocytes of cigarette smokers.

Cigarette smoking is generally believed to be responsible for a substantial number of human health problems. However, the causal relationship between smoking, the induction of biological effects and the extent of health problems among smokers have not been fully documented. Using the recently developed lymphocyte micronucleus (MN) assay, we have evaluated the chromosome aberration frequencies in 67 cigarette smokers and 59 matched non-smoking control subjects. We found that the mean MN frequency (per 100 cells) in the smokers was slightly higher than that found in the non-smokers (0.71 +/- 0.23 and 0.58 +/- 0.05 respectively; p less than 0.08). Factors which contribute to the expression of chromosome aberrations were also investigated. A significant age-dependent increase in MN frequencies was observed in both groups (p less than 0.05). Linear regression analysis showed that the age-dependent effects among smokers (r = 0.54; p less than 0.02) was further enhanced by cigarette consumption (r = 0.62; p less than 0.005). Consumption of low potency 'one-a-day' type multivitamins had no effect on MN frequencies in either sex of non-smokers and in the 1 male smoker who took multivitamins but vitamin intake consistently reduced the MN frequencies among female smokers. Using a challenge assay, fidelity of DNA repair was evaluated. Lymphocytes from both smokers and non-smokers were irradiated with single doses of 0 or 100 cGy of X-rays or with double doses of 100 cGy of X-rays each separated by 15 or 60 min (100/15 or 100/60). Chromosome translocation frequencies were consistently higher after irradiation in lymphocytes from smokers than in those from non-smokers. Statistically significant differences were detected when the cells were irradiated with the double doses of 100 cGy X-rays each separated by 60 min (p less than 0.05). These data suggest that lymphocytes from smokers made more mistakes in the repair of DNA damage than cells from non-smokers. Our studies provide new insights into the genotoxic effects of cigarette smoke and new information which may be useful for understanding the mechanisms for induction of health problems from smoking.

Aging↗
PubMed1991

A computerized diet questionnaire for use in diet health education. 1. Development and validation.

A diet questionnaire was developed in association with a computer program to provide rapid nutritional feedback to the general public. The questionnaire was validated against 16 d of weighted diet records and biochemical variables in blood and urine. The highest Pearson correlation coefficients obtained between the questionnaire and the weighed records were for alcohol, fibre, iron, riboflavin (r 0.74, 0.67, 0.66, 0.66 respectively). Striking sex differences were shown in the results; the trend for higher correlations persisted in females. At least 65% of subjects were classified by questionnaire to within one quintile of the classification by weighed record for the majority of nutrients.

Adolescent↗
PubMed1991

Inhibition of plant glutamine synthetases by substituted phosphinothricins.

Glutamine synthetase (GS) utilizes various substituted glutamic acids as substrates. We have used this information to design herbicidal alpha- and gamma-substituted analogs of phosphinothricin (l-2-amino-4-(hydroxymethylphosphinyl)butanoic acid, PPT), a naturally occurring GS inhibitor and a potent herbicide. The substituted phosphinothricins inhibit cytosolic sorghum GS(1) and chloroplastic GS(2) competitively versusl-glutamate, with K(i) values in the low micromolar range. At higher concentrations, these inhibitors inactivate glutamine synthetase, while dilution restores activity through enzyme-inhibitor dissociation. Herbicidal phosphinothricins exhibit low K(i) values and slow enzyme turnover, as described by reactivation characteristics. Both the GS(1) and GS(2) isoforms of plant glutamine synthetase are similarly inhibited by the phosphinothricins, consistent with the broad-spectrum herbicidal activity observed for PPT itself as well as other active compounds in this series.

Journal Article↗
PubMed1991

The financial status of the Social Security and Medicare programs (1990).

To summarize the major points I have covered: The Social Security and Medicare trust funds are carefully held and monitored by three five member boards of trustees, and each board has two members who represent the public's interest. The combined Social Security trust funds are well financed for many years into the future; however, there is reason to monitor the financing for the disability insurance trust fund; and actions will in all likelihood ultimately be required to assure the long-term financial integrity of the combined OASDI programs over the next 75 years. The Medicare trust funds are adequately financed for the short term; however, the HI program faces serious mid- and long-range financing problems that must be addressed. As a result, there is a strong need for Congress to take remedial action to improve the financing and provide an adequate contingency reserve for the program.

Decision Making↗
PubMed1991

HCV and HEV: the newly identified non-A non-B hepatitis viruses.

The last 2 years have seen dramatic advances in our understanding of the agents responsible for non-A, non-B hepatitis. The family of recognized hepatitis agents now numbers five. In this article, the authors update readers on the characteristics of the two most recent additions, hepatitis C and E, the former posing a potential risk to the dental surgeon.

Cross Infection↗
PubMed1990

Inhibition of Escherichia coli glutamine synthetase by alpha- and gamma-substituted phosphinothricins.

We have investigated the inhibition of Escherichia coli glutamine synthetase (GS) with alpha- and gamma-substituted analogues of phosphinothricin [L-2-amino-4-(hydroxymethylphosphinyl)butanoic acid (PPT)], a naturally occurring inhibitor of GS. These compounds display inhibition of bacterial GS that is competitive vs L-glutamate, with Ki values in the low micromolar range. At concentrations greater than Ki the phosphinothricins caused time-dependent loss of enzyme activity, while dilution after enzyme inactivation resulted in recovery of enzyme activity. ATP was required for inactivation; the nonhydrolyzable ATP analogue AMP-PCP failed to support inhibition of GS by the phosphinothricins. The binding of these inhibitors to the enzyme was also characterized by measurement of changes in protein fluorescence, which provided similar inactivation rate constants k1 and k2 for the entire series of compounds. Rate constants koff for recovery were also determined by fluorescence measurement and were comparable for both PPT and the gamma-hydroxylated analogue GHPPT and significantly greater for the alpha- and gamma-alkyl-substituted compounds. Electron paramagnetic resonance spectra provided information on the interaction of the phosphinothricins with the manganese form of the enzyme in the absence of ATP, and significant binding was observed for PPT and GHPPT. 31P NMR experiments confirmed that enzyme inactivation is accompanied by hydrolysis of ATP, although phosphorylated phosphinothricins could not be detected in solution. The kinetic behavior of these compounds is consistent with a mechanism involving inhibitor phosphorylation, followed by release from the active site and simultaneous hydrolysis to form Pi and free inhibitor.

Adenosine Triphosphate↗
PubMed1990

Surgical ciliated (postoperative maxillary) cysts following mid-face osteotomies.

Surgical ciliated (postoperative maxillary) cysts have been reported extensively as occurring 6 months to 50 years after radical surgery for maxillary sinusitis. Three cases are presented in which these aggressive cysts occurred 3 to 4 years after Le Fort I, II and III mid-face osteotomies. The presentation, treatment and possible aetiology are discussed and some attempt made to clarify the descriptive terms used in the literature.

Adult↗
PubMed1990

Characterisation of the effector cells responsible for the in vitro cytotoxicity of blood leucocytes from aphthous ulcer patients for oral epithelial cells.

This study was designed to identify the cells responsible for the spontaneous cell mediated cytotoxic effect (SCMC) exerted by peripheral blood leucocytes from patients with recurrent aphthous ulceration, towards cultured oral epithelial cells. Peripheral blood leucocytes from recurrent aphthous ulceration patients exerted a significantly greater (p less than 0.01) degree of cytotoxicity towards the oral epithelial target cells than did peripheral blood leucocytes from healthy control subjects, or from patients with non-specific ulceration. Depletion of CD-5 positive cells (T-lymphocytes) resulted in a significant decrease in the SCMC in aphthous patients. Depletion of CD-16 positive cells (NK-cells) produced no significant change in cytotoxicity. T-lymphocytes, therefore, appear to be intimately involved in the in vitro SCMC effect in recurrent aphthous ulceration.

Adolescent↗