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Biomedical subjects

I Taylor

Publications and source records attributed to I Taylor.

At least 19 recordsLinked to original sources
PubMed1992

Life events and breast cancer prognosis.

OBJECTIVE: To determine whether psychosocial stress, in the form of adverse life events and social difficulties, depressive illness, or lack of confiding relationships, shortens the postoperative disease free interval in breast cancer patients. DESIGN: Prospective follow up of a cohort of newly diagnosed breast cancer patients for 42 months after primary surgical treatment, using a life events and social difficulties schedule (LEDS) and assessment of depressive symptomatology (DSM-III). SETTING: Patients recruited from breast clinics in Southampton and Portsmouth were interviewed in their homes. PATIENTS: 204 women (83% of 246 consecutive cases) treated either by mastectomy or wide excision followed by radiotherapy interviewed four, 24, and 42 months after operation. MAIN OUTCOME MEASURES: Hazard ratios for relapse of breast cancer in relation to various measures of psychosocial stress. Relapse was defined as local recurrence or distant metastasis, or both, with histological or radiological confirmation and timed from the month when clinical symptoms began. RESULTS: After adjustment for age and axillary lymph node involvement, the hazard ratio associated with severe life events or social difficulties (excluding "own health" ones), or both, during the year before breast cancer surgery was 0.43 (95% confidence interval 0.20 to 0.93); for those during the follow up period it was 0.88 (0.48 to 1.64). For prolonged major depression before surgery and during the follow up period, hazard ratios were 1.26 (0.49 to 3.26) and 0.85 (0.41 to 1.79) respectively. For absence of a full confidant the figures were 0.93 (0.42 to 2.09) and 0.86 (0.38 to 1.93). CONCLUSION: These results give no support to the theory that psychosocial stress contributes to relapse of breast cancer.

Breast Neoplasms↗
PubMed1992

High-level expression of the cloned genes encoding the subunits of and intact DNA methyltransferase, M.EcoR124.

We have cloned the genes coding for the two subunits (HsdM and HsdS) of the type-I DNA methyltransferase (MTase), M.EcoR124, into the specially constructed expression vector, pJ119. These subunits have been synthesized together as an intact MTase. We have also cloned the individual subunit-encoding genes under the control of the T7 gene 10 promoter or the lacUV5 promoter. High levels of expression have been obtained in all cases. While HsdM was found to be soluble, HsdS was insoluble. However, in the presence of the co-produced HsdM subunit, HsdS was found in the soluble fraction as part of an active MTase. We have partially purified the cloned multi-subunit enzyme and shown that it is capable of DNA methylation both in vivo and in vitro.

Amino Acid Sequence↗
PubMed1992

Purification and biochemical characterisation of the EcoR124 type I modification methylase.

Large scale purification of the type I modification methylase EcoR124 has been achieved from an over-expressing strain by a two step procedure using ion-exchange and heparin chromatography. Pure methylase is obtained at a yield of 30 mg per gm of cell paste. Measurements of the molecular weight and subunit stoichiometry show that the enzyme is a trimeric complex of 162 kDa consisting of two subunits of HsdM (58 kDa) and one subunit of HsdS (46 kDa). The purified enzyme can methylate a DNA fragment bearing its cognate recognition sequence. Binding of the methylase to synthetic DNA fragments containing either the EcoR124 recognition sequence GAAN6RTCG, or the recognition sequence GAAN7RTCG of the related enzyme EcoR124/3, was followed by fluorescence competition assays and by gel retardation analysis. The results show that the methylase binds to its correct sequence with an affinity of the order 10(8) M-1 forming a 1:1 complex with the DNA. The affinity for the incorrect sequence, differing by an additional base pair in the non-specific spacer, is almost two orders of magnitude lower.

Anilino Naphthalenesulfonates↗
PubMed1992

Incidence of arm swelling following axillary clearance for breast cancer.

Arm swelling was measured using volume determination in 118 patients following mastectomy (n = 60) or wide excision (n = 58), both with axillary clearance. The mean age was 60.5 years and the median follow-up was 22.5 months. Axillary clearance removed level III nodes. Axillary irradiation was given to only three patients with extensive (more than 75 per cent) nodal involvement. The incidence of early postoperative complications was 18.6 per cent. The incidence of lymphoedema was 7.6 per cent (nine patients). Three of these patients had early lymphoedema within 6 months of treatment. Arm circumference differences correlated poorly with volume differences. The incidence of lymphoedema following axillary clearance is low and comparable to that for sampling or no axillary surgery.

Adult↗
PubMed1992

Proliferation indices of invasive breast carcinomas after in vivo 5-bromo-2'-deoxyuridine labelling: a flow cytometric study of 75 tumours.

In vivo labelling of human breast tumours with 5-bromo-2'-deoxyuridine and analysis of proliferation by multiparameter flow cytometry is a new tool by which the labelling index, S phase duration (TS) and potential doubling time (Tpot) of the tumour can be estimated. Tumour specimens from 75 patients with invasive breast carcinoma were studied. Six tumours could not be analysed, and the TS and Tpot values could not be calculated for a further 18. The median labelling index (n = 69) was 4.2 per cent. The median TS (n = 51) was 8.7 h and the median Tpot (n = 51) was 8.2 days. The median intra-assay coefficient of variation for determination of the labelling index was 0.29 in five tumours. There were no significant differences in the total labelling index, TS or Tpot when patients were stratified according to lymph node status, tumour size, tumour grade or menopausal status.

Adult↗
PubMed1992

Biodistribution of Lipiodol following hepatic arterial injection.

Thirteen patients undergoing selective coeliac angiography before insertion of an indwelling hepatic arterial cannula underwent injection of 3 ml radiolabelled Lipiodol (2 MBq 131I) into the hepatic artery at the end of the procedure. At subsequent laparotomy 1-9 days later, biopsies were taken from normal liver and metastases. The radioactivity of this material was measured to establish the tumour:liver ratios. Two patients with large metastases (> 10 cm in diameter) had low ratios. In the remainder, the median ratio at 24 h was 1.5:1 (range 1.1-2.5:1; n = 5) and 2.6:1 (range 1.5-64.0:1; n = 6) at 3-9 days. Four patients underwent single photon emission computed tomography, which confirmed selective retention of Lipiodol in small metastases, although no activity was detected in a large deposit (> 15 cm) 10 days after injection. The tumour:liver ratio in the other three patients increased from 3.0-5.6:1 on day 1 to 4.5-7.2:1 on day 6. This study suggests that Lipiodol may be a useful therapeutic delivery agent to small colorectal liver metastases.

Humans↗
PubMed1992

Tissue procoagulant activity may be important in sustaining metastatic tumour growth.

There is strong evidence for an association between the haemostatic system and malignancy. Thus, cancer may adversely affect the host coagulation system while the haemostatic system may play a role in the development of both primary and metastatic tumours. Metastatic growth is not dependent simply on haemodynamic factors, and properties of both the tumour cell and host organ are important determinants of the site of metastatic growth. Previous studies have demonstrated that some organs are preferred sites for metastasis while others are less preferred or resistant. We have measured the procoagulant activity (PCA) of normal rat and human tissues and correlated the results with the previously reported ability of these organs to support metastatic tumour growth. In addition, we determined changes in PCA in rat tissues during oral anticoagulant therapy, and following colonic anastomosis and partial hepatectomy, procedures which are known to affect experimental metastasis. In both rat and human studies, organs which are preferred sites for metastasis had significantly higher PCA than non-preferred organs (P less than 0.001). The PCA of adrenal, lung and colon was significantly reduced by administration of warfarin (P less than 0.001). PCA was significantly (P less than 0.001) increased in both colonic anastomoses and regenerating liver and followed a time course similar to that of the enhanced tumour growth usually seen in these situations. Although the exact source of the procoagulant activity remains to be determined, the results suggest that there is a broad correlation between tissue PCA and the ability of a tissue to support metastatic tumour growth.

Anastomosis, Surgical↗
PubMed1992

Assessment of morbidity from complete axillary dissection.

The importance of axillary dissection as part of the primary surgical procedure in the treatment of operable cases of carcinoma of the breast is established. The morbidity of this procedure, however, is less well documented. A study of 126 women who had had full axillary dissection as part of their initial surgical treatment was undertaken to assess their degree of morbidity in terms of numbness, pain, weakness, swelling, and stiffness. Seventy per cent of cases complained of numbness, 33% of pain, 25% of weakness, 24% of limb swelling, and 15% of stiffness. Objective measurements confirmed decreased sensation in 81%, weakness in 27%, swelling in 10%, and stiffness in 10%. In no case were these symptoms described as severe, though they did have an effect upon the daily lives of 39%. The side effects of full axillary dissection are common and all women should be warned of them prior to surgery; however they are usually mild and therefore should not preclude this procedure as a part of definitive surgical treatment.

Breast Neoplasms↗
PubMed1992

The effect of Warfarin and factor VII on tissue procoagulant activity and pulmonary seeding.

Peri-tumour fibrin is a consistent feature of tumour stroma and is deposited shortly after tumour cell inoculation. Since there are several ways in which fibrin may be beneficial to tumour growth, it is possible that the ability of normal or malignant tissue to generate fibrin may influence metastasis. Many normal tissues and tumour cells possess a procoagulant activity that is due to a complex of tissue factor and factor VII. We have measured this tissue procoagulant activity in normal rats, rats stabilised on Warfarin and similarly anticoagulated animals injected with factor VII. The effect of Warfarin and factor VII administration on pulmonary seeding following injection of MC28 fibrosarcoma cells was also assessed. Procoagulant activity in adrenal, lung and colon was significantly reduced by Warfarin (P less than 0.001). Administration of factor VII significantly increased lung and adrenal tissue procoagulant activity in anticoagulated rats (P less than 0.02). Warfarinised rats had significantly slower primary tumour growth (P less than 0.001) and fewer lung deposits than control animals (P less than 0.001). Injection of factor VII restored pulmonary seeding to control levels (P less than 0.001). Warfarin did not affect the ability of the cells to adhere in vitro and did not reduce the number of tumour cells physically trapped in the lungs after intravenous injection. It is concluded that the procoagulant activity of normal tissues may influence their ability to support tumour growth and that the antimetastatic effect of Warfarin may be at least partly due to a reduction in the availability of the factor VII required for this activity.

Adrenal Glands↗
PubMed1992

Cryopreservation evaluated with mitochondrial and Z line ultrastructure in striated muscle.

Single, intact, frog skeletal muscle fibres and whole frog hearts were quick-frozen on a polished, liquid-He-cooled copper block and examined in the electron microscope after freeze-substitution and freeze-fracture. In both kinds of striated muscle, collapse of the peripheral and intracristal membrane spaces in mitochondria was found to increase with increasing distance from the point of first impact (PFI) of the muscle cells on the cold copper block. The changes correlated with a previously described gradient of Z line and A band cryodamage occurring with distance from the PFI. The findings in thin sections from freeze-substituted preparations were confirmed by freeze-fracture preparations. It is concluded that, since the mitochondrial membrane changes are concurrent with, and follow the same spatial distribution of, other manifest cryoartefacts, the cryoartefactual nature of the mitochondrial changes must be excluded before functional significance is attributed to them. The collapse of mitochondrial membrane spaces as a sensitive indicator of quality of cryopreservation may apply to non-muscle cells as well.

Animals↗
PubMed1992

What are the benefits of routine breast cancer follow-up?

The value of follow-up after potentially curative treatment of breast cancer remains controversial. Recurrence-free women (n = 402) attending a breast clinic over a 3 month period were studied. The women attended 423 appointments, 412 of which were routine. Eleven were requested by the patient or general practitioner (interval appointments). All 11 interval and 19 of the routine appointments resulted in investigations for possible recurrence. Three (27%) interval appointments and four (1%) routine appointments resulted in the diagnosis of a recurrence (P < 10(-5). The attitudes of 285 patients to follow-up were investigated by questionnaire. Two hundred and twenty-three (78%) questionnaires were completed. Regular follow-up in the breast clinic was preferred to attendance only when symptomatic by 190 (85%) women and 169 (76%) preferred regular breast clinic visits to general practitioner follow-up. Most women (n = 174) (81%) said they felt reassured and less anxious having attended the breast clinic. Routine follow-up after potentially curative treatment of breast cancer is inefficient in the detection of recurrence. It is, however, highly rated for providing reassurance and reducing anxiety. Reassurance rather than detection of recurrence may be the most important function of the breast cancer follow-up clinic.

Adult↗
PubMed1992

Loco-regional recurrence and survival after wide local excision, radiotherapy and axillary clearance for early breast cancer.

After breast conservation for early breast cancer which comprised wide local excision, axillary clearance and radiotherapy to the breast, 145 women have been followed prospectively for a median of 42 months. Local recurrence occurred in 11 (7%) and axillary recurrence in three (2%). Distant recurrence has occurred in 32 and accounted for 80% of all first recurrences. Local treatment failure has occurred in three women and would not have been prevented by mastectomy. Loco-regional recurrence in the absence of preceding or synchronous distant disease was unusual and did not pose a significant clinical problem.

Adult↗
PubMed1992

Biodistribution of lipiodol following hepatic arterial injection.

Lipiodol, a derivative of poppy seed oil, has been used angiographically to improve visualisation of small liver tumours. We have utilised this finding to determine whether intrahepatic arterial injection of lipiodol can be used as a vehicle to deliver selectively 131I into liver tumours. Two groups of rats were studied. Group 1 (control, no liver tumour) received 0.1 ml 131I-lipiodol (1 microCi) into the hepatic artery. Animals were killed at regular time intervals over 30 days and organs were submitted to well-counting. Over 90% of activity remained in the liver at 6 h. Eighty per cent activity was lost from the normal liver, to be excreted in the urine over 30 days. Group 2 animals received intraportal injections of 7.5 x 10(5) MC28 sarcoma cells. Multiple liver metastases were present after 14 days. Animals were similarly studied at each time interval and samples from tumour and normal liver were submitted to well-counting. Lipiodol was selectively retained within tumour and cleared from normal liver. 131I-lipiodol may prove valuable as a delivery agent for radio/chemotherapy to liver metastases.

Animals↗
PubMed1992

The relationship between clinical staging, oestrogen receptor status and silver-binding nucleolar organiser regions (AgNOR) in breast carcinoma.

Forty benign and 31 malignant breast tissues were examined using a one stage colloid-stabilising silver technique for argyrophilic nucleolar organiser regions (AgNOR). In 31 patients TNM staging was correlated to AgNOR score. There was a positive correlation with the T-stage and AgNOR score of the tumor (Spearman's rank correlation coefficient = 0.437). The N-stage and AgNOR score for breast cancers (n = 10) were inversely related, and there was a significant difference between the lymph node positive and negative groups (P less than 0.05). No significant relationship was identified between oestrogen receptor negative and positive groups and AgNOR score (P = 0.63). Mean regression analysis suggests that independent of the Bloom's grade, the AgNOR score is an indicator of tumour size.

Breast Diseases↗
PubMed1991

Proliferation characteristics of human colorectal carcinomas measured in vivo.

The cell proliferation kinetics of 100 human colonic and rectal adenocarcinomas have been studied in vivo by bromodeoxyuridine infusion and multiparameter flow cytometry. A total of 97 patients, three with synchronous tumours, consented to receive a single bolus dose of 250 mg between 2.4 and 16 h before curative or palliative surgery. By this method, the ploidy pattern, the total and aneuploid labelling indices (LI), the S phase duration (Ts) and the potential doubling time (Tpot) can be estimated. Of the tumours 48 were diploid and 52 were aneuploid. The mean and median total LI of 100 tumours were 9.0 per cent (range 0.7-22.2 per cent). The mean aneuploid LI was 12.1 per cent (median 12.0 per cent, range 2.0-25.5 per cent), and was significantly higher than the total LI (P = 0.01). The labelling index alone is not a sufficient indicator of proliferation, because the Ts also varies within and between tumours. The intertumour range of the Ts varied from 4.0 to 28.6 h. The mean was 14.1 h and the median was 13.1 h. The mean Tpot was 5.9 days (median 3.9 days) with a range of 1.7-21.4 days. No correlation was found between any kinetic parameters and the Dukes' classification or histological classification. The correlation between proliferation and prognosis will be established in due course.

Adenocarcinoma↗
PubMed1991

Importance of the omentum in the development of intra-abdominal metastases.

Areas of trauma are preferred sites for metastatic tumour growth. In extensive intra-abdominal tumour recurrence the omentum is invariably involved. The importance of the omentum in the development of tumours at sites of intra-abdominal trauma has been investigated. Colonic anastomoses were performed in Hooded-Lister rats with and without omentectomy. Animals received intraluminal or intraperitoneal injections of a syngeneic tumour. With intraluminal injection, tumour occurred at the anastomosis and in the omentum in 38 and 43 per cent of animals respectively but following omentectomy the values were 14 and 9 per cent (omental remnant). With intraperitoneal administration tumour occurred in 53 per cent at the anastomosis and in 79 per cent in the omentum compared with 16 and 29 per cent (in omental remnant) following omentectomy. In this model a reduced ability of an anastomosis to support 'seeded' tumour following removal of the omentum is demonstrated and the development of local recurrence from spilled tumour cells during operation may be enhanced by, or be dependent on, the proximity of the omentum.

Anastomosis, Surgical↗
PubMed1991

c-myc protein product is a marker of DNA synthesis but not of malignancy in human gastrointestinal tissues and tumours.

c-myc is a conserved cellular gene. The gene product is a nuclear-bound 62,000 molecular weight phosphoprotein (p62c-myc). Although p62c-myc levels have been measured in colorectal cancers, little is known about the expression of the protein in upper gastrointestinal tumours and tissues. Studies were performed on tumour and mucosal specimens from 87 patients with colorectal cancer, from two with polyposis coli, from six with squamous oesophageal carcinomas and from 18 with gastric carcinomas. The mean p62c-myc content was measured in units of fluorescence in the G1 diploid and G2 diploid peaks of the cell cycle by multiparameter flow cytometry using the 6E10 antibody. The nuclear p62c-myc content increased with DNA synthesis in tumours and mucosa. G2 levels of p62c-myc were higher in glandular mucosa than in adenocarcinomas. No differences in peak nuclear c-myc expression were found in relation to histological grade or to anatomical site of colorectal tumours. There was a broadly inverse relationship between G2 p62c-myc levels in tumours and mucosa and their in vivo 5-bromo-2'-deoxyuridine labelling indices. Nuclear p62c-myc levels are cell cycle related but the protein has not been shown to be a marker of increased tissue proliferation or of gastrointestinal malignancy. The reduction of the nuclear p62c-myc content of many adenocarcinoma cells compared with glandular mucosa cells suggests that reduced synthesis or nuclear retention of the normal protein may be a factor in the development of gastrointestinal adenocarcinomas, although the mechanism by which this may occur is not clear.

Adenocarcinoma↗