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Biomedical subjects

A M Thompson

Publications and source records attributed to A M Thompson.

At least 109 records · Page 6Linked to original sources
PubMed1992

p53 allele losses, mutations and expression in breast cancer and their relationship to clinico-pathological parameters.

The p53 locus on the short arm of chromosome 17 at 17p 13.1 was examined for loss of heterozygosity, mutation, mRNA and protein expression in 60 primary breast cancers. Allele loss around the p53 locus was detected in 19/45 informative tumours (42%). p53 mutations in the evolutionarily conserved exons 5 to 9 were detected in 17/60 (28%) by amplification mismatch and confirmed by direct DNA sequencing. p53 mRNA expression was detected by Northern blot in 36/59 (61%) of tumours, and p53 protein expression using antibody 1801 on frozen-tissue sections in 13/44 of the tumours examined. p53 mutation was significantly associated with oestrogen-receptor-poor tumours (p less than 0.01) and hence with poor prognosis, but not with other clinical or pathological parameters. There was no statistical correlation between loss of heterozygosity around the p53 locus at 17p13.1 and p53 mutation. Furthermore, p53 mutation was not associated with p53 expression detected by immunohistochemical staining with antibody 1801 or as p53 mRNA. In addition, events on 17p (allele losses, p53 mutation, p53 expression) were independent of c-erbB-2 expression. In breast cancer, by contrast with colorectal, lung and ovarian cancer, there appears to be no clear association between p53 DNA abnormalities and p53 expression.

Alleles↗
PubMed1992

Safety of fibreoptic endoscopy: analysis of cardiorespiratory events.

Cardiorespiratory function during upper gastrointestinal endoscopy and colonoscopy was studied prospectively in 164 patients. Cardiorespiratory events, which were defined as oxygen saturation < 90 per cent, electrocardiographic changes, heart rate < 50 or > 100 beats/min and systolic blood pressure < 100 mmHg, occurred in 111 patients. In 24 of these, changes were attributed solely to intravenous sedation. In the remaining 140 patients, events were noted in 34 (52 per cent) of 66 upper gastrointestinal endoscopies and during 53 (72 per cent) of 74 colonoscopies. One patient suffered a myocardial infarction during colonoscopy. Although cardiorespiratory events were common (111 of 164; 68 per cent), the actual morbidity rate was low (one of 164; 0.6 per cent). Cardiorespiratory events were significantly more common in patients with a history of cardiac disease for both upper gastrointestinal endoscopy and colonoscopy (overall chi 2 = 7.41, 1 d.f., P < 0.05) and more common for oesophageal dilatation than for diagnostic endoscopy (chi 2 = 5.56, 1 d.f., P < 0.05). It is recommended that patients with a history of cardiac problems undergoing upper gastrointestinal endoscopy or colonoscopy and all those requiring therapeutic endoscopy should be monitored carefully to allow early detection of cardiorespiratory events, and that oxygen should be administered routinely.

Adult↗
PubMed1992

Induction of heat shock protein in interdental cells by hyperthermia.

The effect of hyperthermia on induction of the 72 kilodalton (kDa) heat shock protein (HSP72) was examined in interdental cells of the guinea pig cochlea. After being immersed in a water bath of either normal body temperature (37 degrees C, control condition) or 43 degrees C (hyperthermic condition), animals were killed either 0, 1, 2, 6, or 18 hours later. Cochlear sections were incubated with a monoclonal antibody raised against HSP72 and relative staining densities were quantified with a light microscopic image analysis system. Optical densities of the interdental cell region of animals receiving hyperthermia treatment were significantly greater than those of animals in the control group. Further analysis revealed that levels of HSP72 immunoreactivity began increasing by 1 hour after hyperthermia and continued to increase thereafter, to reach maximal levels at 6 hours. The maximal levels were maintained for the rest of the experiment--18 hours. The results indicate that hyperthermia leads to an increase in the synthesis of HSP72 in guinea pig interdental cells.

Animals↗
PubMed1991

Projections from the posteroventral cochlear nucleus to the superior olivary complex in guinea pig: light and EM observations with the PHA-L method.

The efferent neural projections from posteroventral cochlear nucleus to the superior olivary complex in guinea pig were examined with the Phaseolus vulgaris-leucoagglutinin anterograde tract-tracing method. Light microscopic analysis demonstrated that the posteroventral cochlear nucleus of guinea pig bilaterally projects to the superior para-olivary nucleus and the rostral, medioventral, and lateroventral peri-olivary regions. Ipsilaterally, the posteroventral cochlear nucleus projects to the lateral superior olive, the caudal peri-olivary region, and areas immediately surrounding the capsule of the lateral superior olive. Contralaterally, the posteroventral cochlear nucleus projects to the medial nucleus of the trapezoid body. All of these projection axons travel in the trapezoid body and their terminals make, primarily, en passant endings upon their targets. Exclusively within the contralateral medial nucleus of the trapezoid body, some neurons terminate also in calyceal endings. The assumption that immunolabeled structures observed with light microscopy made actual synaptic contact in their respective target areas was confirmed with electron microscopy. With postembedding immunocytochemical procedures applied to thin sections, the electron microscope revealed labeled synaptic vesicles and pre- and postsynaptic membrane specializations. The projection pattern from posteroventral cochlear nucleus was found to be topographically organized in three distinct regions. The more dorsally located neurons of the posteroventral cochlear nucleus terminated dorsomedially in the ipsilateral lateral superior olive, ventromedially in the contralateral superior para-olivary nucleus, and medially in the contralateral medioventral peri-olivary region. The more ventrally located neurons of the posteroventral cochlear nucleus terminated dorsolaterally in the ipsilateral lateral superior olive, dorsolaterally in the contralateral superior para-olivary nucleus, and laterally in the contralateral medioventral peri-olivary region.

Animals↗
PubMed1991

Posteroventral cochlear nucleus projections to olivocochlear neurons.

The presence of ascending auditory inputs from the posteroventral cochlear nucleus (PVCN) to olivocochlear neurons was examined in guinea pig by using the combination Phaseolus vulgaris-leucoagglutinin (PHA-L) anterograde and horseradish peroxidase (HRP) retrograde tract-tracing technique. By labeling the somata of olivocochlear neurons after injection of HRP into the cochlea and simultaneously labeling terminal endings of PVCN efferent neurons after injection of PHA-L into PVCN, we observed neuronal connections between these two elements within all regions of the superior olivary complex known to contain olivocochlear neurons. These regions include the superior paraolivary nucleus, medial nucleus of the trapezoid body, lateral superior olive, and periolivary regions. All possible projection patterns regarding side of input and output of both large (four combinations) and small (two combinations) olivocochlear neurons were observed. However, the most frequently observed pattern was the PVCN projection to a contralaterally located and contralaterally projecting, large olivocochlear neuron. Thus the most prevalent pattern demonstrated a feedback pathway that crossed the brainstem twice. Additional patterns demonstrated pathways that fed back to the same cochlea as well as pathways that fed forward to the opposite cochlea.

Animals↗
PubMed1991

Effective surgical treatment for mammary duct fistula.

Forty-two patients with 43 mammary duct fistulae, including 23 with a history of at least one previous unsuccessful operation, were treated by excision of the involved duct and fistula alone (15 fistulae) or excision of the fistula combined with total duct excision (28 fistulae). The wounds were closed primarily with antibiotic cover. Two patients had a minor wound infection which settled within 1 month of surgery; one patient developed superficial necrosis of the nipple and one patient required a second operation to excise a discharging sinus. No fistula recurrence has been identified after a median follow-up of 2.5 years. Excision of the involved duct and fistula alone, or excision of the fistula combined with total duct excision performed with antibiotic cover, is probably the treatment of choice for mammary duct fistula.

Adult↗
PubMed1991

Transforming growth factor beta 1 is implicated in the failure of tamoxifen therapy in human breast cancer.

Transforming growth factor-beta 1 (TGF-beta 1) is inhibitory for breast epithelial cells in vitro and treatment of breast cancer cell lines with tamoxifen results in a rise in TGF-beta 1 mRNA expression with associated inhibition of cell growth. To study whether these findings apply in vivo we examined TGF-beta 1 mRNA expression in an oestrogen-dependent mouse xenograft system following systemic treatment of the mice with tamoxifen. In agreement with in vitro studies. TGF-beta 1 mRNA expression was sustained at high levels and associated with a reduction in tumour size. A subsequent study of breast tumour tissue from 56 patients demonstrated high levels of TGF-beta 1 mRNA in 45 of the tumours. High expression was found to correlate with premenopausal status, but not with tumour oestrogen receptor content or other parameters. In a subgroup of 11 patients who had received tamoxifen therapy for 3 to 6 months prior to surgery, unexpectedly high levels of TGF-beta 1 mRNA were demonstrated in tumours increasing in size and unresponsive to tamoxifen. Data from this study indicate that in patients with breast cancer, TGF-beta 1 in the tumour may not behave as in vitro and xenograft studies have suggested. We speculate that failure of tamoxifen therapy may be due to failure of the autocrine inhibitory functions of TGF-beta 1 either alone or in combination with paracrine stimulation of stromal cells or angiogenesis and localised immunosuppression. Further studies of active TGF-beta 1, TGF-beta receptors and the interactions with other growth factors will be required to elucidate the precise role of TGF-beta 1 in human breast cancer and in the failure of tamoxifen therapy.

Adult↗
PubMed1991

BAY u3405 an antagonist of thromboxane A2- and prostaglandin D2-induced bronchoconstriction in the guinea-pig.

1. The novel thromboxane (TX) antagonist, BAY u3405, has been evaluated against bronchoconstriction induced by the TXA2 mimetic U-46619, prostaglandin D2 (PGD2), 5-hydroxytryptamine (5-HT), leukotriene D4 (LTD4) and histamine in the guinea-pig in vivo by use of a modification of the model described by Konzett & Rössler. 2. When given intravenously (i.v.) at 30 or 100 micrograms kg-1, U-46619 caused 80% maximal bronchoconstriction in most animals. In contrast, PGD2 caused a smaller 40%-50% maximal bronchoconstriction at the highest dose tested (300 micrograms kg-1, i.v.). 3. BAY u3405, given intravenously, orally (p.o.) or by aerosol antagonized U-46619-induced bronchoconstriction in a dose-related manner. The approximate ID50 values were 600 micrograms kg-1, i.v., 1.7 mg kg-1 p.o. and 0.1% w/v 20 breaths by aerosol. 4. BAY u3405 had similar inhibitory activities against U-46619-induced bronchoconstriction and hypertension suggesting that it had no preferential activity on the airways. 5. When given intravenously BAY u3405 antagonized the bronchoconstrictor effect of intravenous PGD2 with ID50 values between 30-100 micrograms kg-1. 6. The action of BAY u3405 (10 mg kg-1, p.o.) was long lasting, causing significant inhibition of U-46619-induced bronchoconstriction 7 h after dosing. 7. At 1 mg kg-1, i.v., a dose that abolished the response to U-46619 and PGD2, BAY u3405 had no effect on histamine-, 5-HT- or LTD4-induced bronchoconstriction. 8. BAY u3405 potently and selectively antagonized U-46619- or PGD2-induced bronchoconstriction in the Konzett-Rössler model of guinea-pig lung function. It should therefore prove to be a useful tool for defining the role of TXA2- and PGD2 in airway diseases such as asthma.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Wound compression pads are of no value after local anaesthetic breast biopsy.

In a randomised study of 120 patients undergoing breast biopsy, wound compression pads did not reduce the frequency of postoperative bruising or haematoma formation, and 12% of the 62 patients having pads had complaints regarding their use. Wound compression pads are of no value after local anaesthetic breast biopsy.

Anesthesia, Local↗
PubMed1990

Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis.

The DNA of paired tumour and blood leucocyte samples from a large series of breast cancer patients was analysed to map regions of loss of heterozygosity on chromosome 17. The high frequency of loss of heterozygosity on 17p was confirmed, and a third of informative tumours had also lost an allele at the long arm locus THH59. On the short arm two distinct regions of loss of heterozygosity were identified, in bands p13-3 and p13-1. The latter probably involves the structural gene p53, which has been implicated as an oncogene or as a tumour suppressor in various human cancers. 17p 13-3, however, showed a significantly higher frequency of loss of heterozygosity, and there was no correlation between allele losses at the two sites. Nevertheless, loss of heterozygosity at 17p 13-3 is associated with overexpression of p53 mRNA, suggesting the existence of a gene some 20 megabases telomeric of p53 that regulates its expression. Lesions of this regulatory gene seem to be involved in the majority of breast cancers.

Alleles↗
PubMed1990

Telomere reduction in human colorectal carcinoma and with ageing.

We have hypothesized that end-to-end chromosome fusions observed in some tumours could play a part in genetic instability associated with tumorigenesis and that fusion may result from the loss of the long stretches of G-rich repeats found at the ends of all linear chromosomes. We therefore asked whether there is telomere loss or reduction in common tumours. Here we show that in most of the colorectal carcinomas that we analysed, there is a reduction in the length of telomere repeat arrays relative to the normal colonic mucosa from the same patient. We speculate on the consequences of this loss for tumorigenesis. We also show that the telomere arrays are much smaller in colonic mucosa and blood than in fetal tissue and sperm, and that there is a reduction in average telomere length with age in blood and colon mucosa. We propose that the telomerase is inactive in somatic tissues, and that telomere length is an indicator of the number of cell divisions that it has taken to form a particular tissue and possibly to generate tumours.

Adenoma↗