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T J Anderson

Publications and source records attributed to T J Anderson.

At least 145 records · Page 8Linked to original sources
PubMed1995

Systemic nature of endothelial dysfunction in atherosclerosis.

Vascular endothelium plays a pivotal role in the maintenance of vasodilation and the inhibition of platelet aggregation and smooth muscle cell proliferation through the release of nitric oxide and other factors. Extensive data have demonstrated abnormalities in coronary endothelial function in the epicardial coronary arteries in patients with atherosclerosis or risk factors for atherosclerosis. This dysfunction leads to abnormal vasoconstriction and platelet aggregation, which likely play a role in producing ischemia in patients with coronary artery disease. Invasive techniques have been available to assess endothelium-dependent vasodilator responses in the coronary arteries. However, until recently little has been known about endothelial responses in the peripheral vasculature, as methods to assess this have not been readily available. The hypothesis that endothelial dysfunction is a systemic process is explored, and new noninvasive methods of assessing endothelial function are discussed.

Arteriosclerosis↗
PubMed1995

The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion.

BACKGROUND: Patients with coronary artery disease and abnormalities of serum lipids often have endothelial vasodilator dysfunction, which may contribute to ischemic cardiac events. Whether cholesterol-lowering or antioxidant therapy can restore endothelium-dependent coronary vasodilation is unknown. METHODS: We randomly assigned 49 patients (mean serum cholesterol level, 209 +/- 33 mg per deciliter [5.40 +/- 0.85 mmol per liter]) to receive one of three treatments: an American Heart Association Step 1 diet (the diet group, 11 patients); lovastatin and cholestyramine (the low-density lipoprotein [LDL]-lowering group, 21 patients); or lovastatin and probucol (the LDL-lowering-antioxidant group, 17 patients). Endothelium-dependent coronary-artery vasomotion in response to an intracoronary infusion of acetylcholine (10(-8) to 10(-6) M) was assessed at base line and after one year of therapy. Vasoconstrictor responses to these doses of acetylcholine are considered to be abnormal. RESULTS: Treatment resulted in significant reductions in LDL cholesterol levels of 41 +/- 22 percent in the LDL-lowering-antioxidant group and 38 +/- 20 percent in the LDL-lowering group (P < 0.001 vs. the diet group). The maximal changes in coronary-artery diameter with acetylcholine at base line and at follow-up were -19 and -2 percent, respectively, in the LDL-lowering-antioxidant group, -15 and -6 percent in the LDL-lowering group, and -14 and -19 percent in the diet group (P < 0.01 for the LDL-lowering-antioxidant group vs. the diet group; P = 0.08 for the LDL-lowering group vs. the diet group). (The negative numbers indicate vasoconstriction). Thus, the greatest improvement in the vasoconstrictor response was seen in the LDL-lowering-antioxidant group. CONCLUSIONS: The improvement in endothelium-dependent vasomotion with cholesterol-lowering and antioxidant therapy may have important implications for the activity of myocardial ischemia and may explain in part the reduced incidence of adverse coronary events that is known to result from cholesterol-lowering therapy.

Acetylcholine↗
PubMed1995

Are mitochondria inherited paternally in Ascaris?

Mitochondrial DNA (mtDNA) is finding increasing usage as a tool for studying the systematics, population genetics and epidemiology of parasitic helminths, and is generally assumed to be inherited maternally. Yet two features of Ascaris biology--fertilization by large amoeboid sperm and some novel aspects of sperm mitochondria--suggest a paternal component to mitochondrial inheritance in this organism. In this study, we compare mtDNA restriction patterns of parental worms with those of their progeny but find no evidence for paternal inheritance. We suggest that sperm-derived mitochondria are actively destroyed or outcompeted by maternal organelles in the zygote.

Animals↗
PubMed1995

Disregulation of urokinase plasminogen activator gene in breast cancer.

Disregulation of urokinase plasminogen activator (uPA) was assessed in 134 breast cancer specimens. Overexpression of uPA was determined by immunohistochemistry using the specific monoclonal antibody, #394. Gene amplification was assessed by differential polymerase chain reaction, using primers designed to amplify a 111 bp segment of the uPA gene. Overexpression of uPA was detected in 33% of breast cancers, including 4 of 21 in situ carcinomas, 7 of 14 lobular and 2 of 10 tubular carcinomas. Overexpression of uPA did not correlate with the presence or absence of oestrogen receptors. uPA gene amplification was not detected in any cancer. We conclude that uPA gene amplification is not a major mechanism instigating uPA overexpression in breast cancer, and that overexpression is likely to be controlled by other mechanisms.

Adenocarcinoma↗
PubMed1995

Ascaris infections in humans from North America: molecular evidence for cross-infection.

Cases of human Ascaris infection occur sporadically in areas such as N. America and Western Europe, where this parasite is thought to be non-endemic. Clinical case histories suggest that many of these cases may be cross-infections from pigs. I describe patterns of variation in the ribosomal DNA of Ascaris from 9 such cases. For comparative purposes, I also describe patterns of variation in parasites obtained from pigs and humans from worldwide locations. A Hae III restriction site distinguishes two classes of rDNA repeats; repeats bearing this restriction site were found in > 96% of parasites from pig populations worldwide and in all 9 worms from humans in N. America. In contrast, repeats bearing this restriction site were detected in < 2% of parasites from humans in endemic areas. The molecular data clearly incriminate pigs as the source of infection in the N. American cases. I discuss evolutionary and public health implications of incomplete host fidelity in Ascaris.

Adult↗
PubMed1995

Mitochondrial DNA and Ascaris microepidemiology: the composition of parasite populations from individual hosts, families and villages.

Patterns of genetic subdivision in parasite populations can provide important insights into transmission processes and complement information obtained using traditional epidemiological techniques. We describe mitochondrial sequence variation in 265 Ascaris collected from 62 individual hosts (humans and pigs) from 35 households in 3 Guatemalan locations. Restriction mapping of individual worms revealed 42 distinct mitochondrial genotypes. We ask whether the mitochondrial genotypes found in worms from individual hosts, from families of hosts and from villages represent random samples from the total Ascaris population. Patterns of genetic subdivision were quantified using F-statistics, while deviations from the null hypothesis of randomness were evaluated by a simple resampling procedure. The analysis revealed significant deviations from panmixia. Parasite populations were strongly structured at the level of the individual host in both humans and pigs: parasites bearing the same mitochondrial genotype were found more frequently than would be expected by chance within hosts. Significant heterogeneity was also observed among populations from different villages, but not from different families within a village. The clustering of related parasites within hosts suggests a similar clustering of related infective stages in the environment and may explain why sex ratios in Ascaris are female-biased. We discuss aspects of Ascaris biology which may lead to the observed patterns.

Animals↗
PubMed1994

Ultrasonography as a method of measuring breast tumour size and monitoring response to primary systemic treatment.

Accurate measurement of change in tumour size is a prerequisite for the use of response-based regimens of primary systemic therapy for breast cancer. This study evaluated the accuracy of clinical assessment, mammography and ultrasonography in measuring tumour size and in monitoring response to treatment. Size was determined during the week preceding surgery and actual size measured from resected specimens. Sequential measurements were performed in 35 patients undergoing primary systemic treatment. There was moderate correlation between pathological and clinical size (n = 51, r2 = 0.68, P < 0.0001). Close correlation with pathological tumour size was observed for mammographic (n = 45, r2 = 0.84, P < 0.0001) and ultrasonographic (n = 52, r2 = 0.89, P < 0.0001) tumour size. Response was correctly evaluated by clinical assessment in 31 of 35 patients, by mammography in 20 of 35 and by ultrasonography in 31 of 35. Actual tumour size can be measured accurately by available imaging techniques but ultrasonography is the most practical and accurate method for monitoring response.

Adolescent↗
PubMed1994

Patterns of cyclic AMP binding in normal human breast.

Cyclic AMP binding proteins have been measured in normal breast tissue, in a variety of physiological conditions including resting state (69 cases), pregnancy (15 cases), lactation (4 cases), post-lactational involution (6 cases), and prolonged involution (10 cases). Levels varied greatly within the groups but median values were elevated in pregnancy, lactation, and post-lactational involution as compared with the resting and prolonged involutionary states. The proportion of different types of cyclic AMP binding proteins also differed between groups. Resting breast showed approximately equal amounts of type I and II whereas pregnant and postlactational involuting breast tissue had an increased proportion of type I binding, and the prolonged involutionary state tended to be associated with low type I. Within the subgroup of nulliparous resting breasts, the proportion of type I cyclic AMP binding protein was significantly elevated during the second half of the menstrual cycle compared with the first (p < 0.05). There were also significant positive associations between the level of epithelial proliferation and both total (p < 0.015) and type I (p < 0.002) cyclic AMP binding. This represents the strongest of association thus far reported between signalling systems and proliferation in the normal breast.

Breast↗
PubMed1994

Nitric oxide and nitrovasodilators: similarities, differences and potential interactions.

Many similarities exist between the exogenous nitrates and endothelium-derived relaxing factor, which is nitric oxide or a thiol derivative. Both act by way of guanylate cyclase, which increases intracellular concentrations of cyclic guanosine monophosphate, resulting in smooth muscle cell relaxation and antiplatelet effects. Thiols may be important in the biotransformation of exogenous nitrates and other intracellular processes involving nitric oxide. As such, important interactions might be expected between nitrates and endothelium-dependent processes that involve nitric oxide. This review explores the mechanisms of action, biologic effects and potential interactions between nitrates and endothelium-derived relaxing factor.

Animals↗
PubMed1994

Consistency of histopathological reporting of breast lesions detected by screening: findings of the U.K. National External Quality Assessment (EQA) Scheme. U. K. National Coordinating Group for Breast Screening Pathology.

The aim of the scheme was to determine consistency of histopathological reporting in the United Kingdom National Breast Screening Programme. This external quality assessment scheme involved 51 sets of 12 slides which were circulated to 186-251 pathologists at intervals of 6 months for 3 years. Participants recorded their diagnoses on standard reporting forms, which were submitted to the U.K. National Cancer Screening Evaluation Unit for analysis. A high level of consistency was achieved in diagnosing major categories of breast disease including invasive carcinoma and the important borderline lesions, radial scar and ductal carcinoma in situ (DCIS), the latter exceeding a national target set prior to the onset of the scheme. Atypical hyperplasia (AH) was reported with much less consistency although, where it was the majority opinion, over 86% of diagnoses were of benign disorders and only 14% were of DCIS. Inconsistency was encountered in subtyping and measuring DCIS, the former apparently due to current uncertainties about classification and the latter to poor circumscription, variation in size in different sections and merging with zones of AH. Reporting prognostic features of invasive carcinomas was variable. Measurement of size was achieved with adequate consistency except in a small number of very poorly circumscribed tumours. Grading and subtyping were inconsistent although the latter was not specifically tested and will be the subject of future study. Members of the National Coordinating Group achieved greater uniformity than the remainder of the participants in all diagnostic categories, but both groups experienced similar types of problem. Our findings suggest that participation in the scheme improves diagnostic consistency. In conclusion, consistency in diagnosing invasive carcinoma and radial scar is excellent, and good in DCIS, but improvements are desirable in diagnosing atypical hyperplasia, classifying DCIS and reporting certain prognostic features of invasive tumours. Such improvements will require further research, the development of improved diagnostic criteria and the dissemination of clearer guidelines.

Breast↗
PubMed1994

Critical determination of the frequency of c-erbB-2 amplification in breast cancer.

Tissues from 323 methacarn-fixed and paraffin-embedded breast cancers were assessed for c-erbB-2 gene amplification by differential polymerase chain reaction (dPCR). The sensitivity of dPCR was ascertained using cell lines with c-erbB-2 amplification, and the relationship between dPCR ratio value and gene copy number was established. In clinical material the technique was not affected by the DNA contribution of normal tissue elements or by cancer DNA ploidy change. c-erbB-2 gene amplification was detected in 55% of invasive cancers and in 66% of in situ cancers. c-erbB-2 protein overexpression in breast cancer cells, as determined by specific immunohistochemistry, was only detected in 11% of invasive cancers and 43% of in situ cancers. Comparisons show that a substantial number of cancers with c-erbB-2 amplification lack detectable protein overexpression. This illustrates the complex nature of c-erbB-2 gene disregulation in cancer and suggests that multiple combinations of biological events and consequences are possible.

Aged↗
PubMed1994

The Edinburgh randomised trial of breast cancer screening: results after 10 years of follow-up.

The Edinburgh Randomised Trial of Breast Cancer Screening recruited 44,288 women aged 45-64 years into the initial cohort of the trial during 1978-81, and 10 years of follow-up is now complete. A total of 22,944 women were randomised into the study group and were offered screening for 7 years; the remaining women formed the control group. After 10 years, breast cancer mortality is 14-21% lower in the study group than in the controls depending on the precise definition of the end point. These differences are not statistically significant; for breast cancer as the underlying cause of death the relative risk is 0.82 (95% confidence interval 0.61-1.11). Rates of locally advanced and metastatic cancer were substantially lower in the study group, but screening has failed to achieve marked reductions in rates of small node-positive cancers. Those women who accepted the final invitation to screening have been monitored over the 3 year period prior to their first screen under the UK service screening programme. Interval cases, expressed as a proportion of the control incidence, increased from 12% in the first year to 67% in the third year. The reduction in breast cancer mortality for older women (aged at least 50 years) is the same as that for the total study group for this duration of follow-up. For analyses of breast cancer mortality in younger women updates recruited to the trial from 1982 to 1985 (10,383 women with 6-8 years' follow-up) have been included. The reduction in breast cancer mortality for women aged 45-49 years at entry was 22% (relative risk = 0.78, 95% confidence interval = 0.46-1.31).

Breast Neoplasms↗
PubMed1994

Cortical control of saccades and fixation in man. A PET study.

To identify cortical regions activated during saccades and visual fixation, regional cerebral blood flow (rCBF) was measured in eight healthy subjects using C15O2 PET during the performance of three tasks: (i) central fixation; (ii) reflexive saccades to random targets; (iii) remembered saccades to locations of recent target appearance. Significant rCBF increases were identified using analysis of covariance and the t statistic (P < 0.001). Compared with central fixation there was activation of striate and extra-striate cortex, posterior parietal cortex (PPC) and frontal eye fields (FEF) during both reflexive and remembered saccades. During remembered saccades there was additional activation of supplementary motor area (SMA), insula, cingulate, thalamus, midbrain, cerebellum and right superior temporal gyrus (Brodmann's area 22). Compared with the individual saccadic tasks, central fixation activated extensive regions of ventromedial (areas 10, 11 and 32) and anterolateral (areas 8, 9, 10, 45 and 46) prefrontal cortex, and foveal visual cortex. We conclude that FEF and PPC are associated with the generation of both reflexive and remembered saccades, with SMA additionally involved during remembered saccades. Sustained voluntary fixation is mediated by prefrontal cortex.

Adult↗
PubMed1993

Role of endothelium in ischemic coronary syndromes.

The recent discovery that the endothelium synthesizes several powerful vasodilators, including prostacyclin and endothelium-derived relaxing factor, has substantially changed our view of the importance of the vascular endothelium and the perspective from which we consider the mechanisms of vascular control. It is now known that the vascular endothelium plays a key role in circulatory homeostasis through its ability to sense the local vascular milieu and respond to it by the synthesis and release of a variety of biologically active substances. The endothelium influences not only vascular tone, but also vascular remodeling via the production of growth-promoting and growth-inhibiting substances; hemostasis and thrombosis through antiplatelet, anticoagulant, and fibrinolytic effects; and inflammation through the expression of chemotactic and adhesion molecules on the cell membrane. In diseases such as atherosclerosis, however, these functions of the endothelium are impaired and may even become counterproductive and disease-promoting. The "activated" or injured endothelial cells paradoxically become prothrombotic, growth-promoting, and leukocyte-adhesive. The endothelium also loses its vasodilating ability, rendering the underlying vascular smooth muscle susceptible to a preponderance of vasoconstrictive forces. It is now recognized that these disturbances in endothelial function are principal players in the ischemic manifestations of coronary artery disease. Endeavors to modify or reverse endothelial dysfunction may therefore be of significant therapeutic benefit in the treatment of myocardial ischemia. This review outlines several important insights into the biology of the arterial wall that are currently being applied to the study of coronary artery disease in humans.

Animals↗
PubMed1993

Specimen-orientated radiography helps define excision margins of malignant lesions detected by breast screening.

Eighty patients with impalpable breast lesions detected by mammographic screening underwent hookwire-guided wide local excision. Excision specimens were orientated with Ligaclips and submitted to radiography; if, on the specimen radiograph, the mammographic lesion crossed any visible margin, further tissue was excised. Clear histological margins were obtained on the initial excision in 52 (68 per cent) of 77 carcinomas. After inspection of the orientated specimen radiograph, further tissue was excised from 22 patients; this significantly increased the rate of complete excision to 86 per cent (P < 0.01). Significantly more patients with invasive cancer had a complete excision than those with ductal carcinoma in situ (52 of 57 versus 14 of 20, P < 0.02).

Breast↗