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Biomedical subjects

P Prior

Publications and source records attributed to P Prior.

At least 37 records · Page 2Linked to original sources
PubMed1995

Bladder tumours following chemotherapy and radiotherapy for ovarian cancer: a case-control study.

A collaborative group of cancer registries and hospitals carried out a case-control study of tumours of the bladder in women who had previously been treated for ovarian cancer. A total of 63 cases of bladder tumours were identified, and 188 controls were selected matching for age, year of ovarian cancer diagnosis and survival time. Full details of the treatment for ovarian cancer were sought for both cases and for controls. The risk of bladder tumours was increased for patients who had been treated by radiotherapy alone (1.9; 95% confidence interval, 0.77-4.9), by chemotherapy alone (3.2; 0.97-10), and by chemotherapy and radiotherapy (5.2; 1.6-16), when comparison was made with patients treated only by surgery. Patients treated by chemotherapy were separated into 2 groups according to whether they had received cyclophosphamide. Among those who had, there was a clear increase in risk (approximately 4-fold) regardless of whether or not they had also received radiotherapy. For those who received only other drugs, risk was increased substantially among patients who had also been treated by radiation, as compared with patients treated by surgery alone, and those who had received radiotherapy only. Both melphalan and thiotepa were implicated as potential bladder carcinogens on the basis of these results. The estimated risk of bladder tumours due to cyclophosphamide was more than twice the risk following radiation to the bladder, and it appeared substantially earlier. For both agents, the risk continued to increase more than 10 years after treatment began.

Aged↗
PubMed1995

Is the three year breast screening interval too long? Occurrence of interval cancers in NHS breast screening programme's north western region.

OBJECTIVE: To report the detection rate of interval cancers in women screened by the NHS breast screening programme. DESIGN: Detection of interval cancers by computer linkage of records held by the screening centres in the North Western Regional Health Authority with breast cancer registrations at the regional cancer registry. SETTING: North Western Regional Health Authority. SUBJECTS: 137,421 women screened between 1 March 1988 and 31 March 1992 who had a negative screening result. RESULTS: 297 invasive interval cancers were detected. The rate of detection of interval cancers expressed as a proportion of the underlying incidence was 31% in the first 12 months after screening, 52% between 12 and 24 months, and 82% between 24 and 36 months. CONCLUSION: The incidence of interval cancers in the third year after breast screening approaches that which would have been expected in the absence of screening and suggests that the three year interval between screens is too long.

Breast Neoplasms↗
PubMed1995

Correlation between seizure intensity and stress protein expression after limbic epilepsy in the rat brain.

Induction of heat shock/stress proteins is a key feature of a universal mechanism of cellular defence to injury known as the "stress response". The present study investigated whether heat shock protein expression correlates with the extent of neuronal injury inflicted by increasingly intense seizure activity. Limbic epilepsy was elicited by injecting intraperitoneally 8, 10 or 12 mg/kg kainic acid in adult Sprague-Dawley rats, resulting in graded degrees of seizure intensity and duration that closely correlated with the respective dose. Stress protein expression was investigated by immunocytochemistry and western blot analysis of microdissected brain areas with specific antibodies directed against representative members of three major classes of stress proteins, i.e. heat shock protein 72, heat shock protein 90 and heat shock protein 27, respectively. Heat shock protein 72 was absent in the brains of control animals, but markedly induced after limbic seizures in neurons of the limbic system, cortex, striatum and thalamus, with peak levels at 24 h. An increasing degree of seizure intensity caused a graded increase of heat shock protein 72 levels with a sequence reflecting the rank order of kainic acid susceptible hippocampal subpopulations. In contrast to heat shock protein 72, heat shock protein 90 was markedly expressed and equally abundant in all brain areas of untreated control animals and at any time point investigated following limbic seizures. Heat shock protein 27 was not detected in the brain of untreated animals nor following epilepsy. The present investigations demonstrate that the induction threshold of heat shock protein 72 in specific neuronal subpopulations clearly correlates with seizure intensity and duration. In addition, our experiments also define a narrow range of heat shock protein 72 expression with an upper limit beyond which heat shock protein 72 synthesis sharply declines. These findings reflect the risk of hippocampal neurons to undergo limbic seizure induced neuronal degeneration. It remains to be determined whether heat shock protein 72 expression is only a valuable marker for reversible neuronal injury or actually confers a neuroprotective effect.

Animals↗
PubMed1995

Childhood cancer and parental use of alcohol and tobacco.

Reported consumptions of alcohol and tobacco for the parents of 1641 children who died with cancer in England and Wales during the period 1977 to 1981 were compared with similar information for the parents of 1641 control subjects. Consumption of alcohol by fathers was not associated with an increased risk of childhood cancer (relative risk (RR)) = 1.05; 95% confidence interval (CI): 0.86 to 1.28), but for daily consumption of cigarettes was not shown to be associated with an increased risk and consumption of alcohol was associated with a relatively low cancer risk (RR = 0.82; 95% CI: 0.70 to 0.96). Relations between maternal consumption of cigarettes and birth weights suggested that the smoking data were equally reliable for case patients and control subjects.

Alcohol Drinking↗
PubMed1995

Prospects for the secondary prevention of colorectal cancer: screening by flexible sigmoidoscopy?

It may be useful to draw an analogy between the proposed screening programme for colorectal cancer and the cervical cancer screening programme. Both tumours show a spectrum of histological abnormalities consistent with a premalignant phase. The natural history of these premalignant lesions is poorly understood and although some will progress, if untreated, to invasive disease, most will not. Light microscopy cannot confidently distinguish which cases will progress and which will regress, and clinicians are therefore obliged to treat all. This will result in the destruction of many lesions of uncertain malignant potential. The secondary prevention of cervical cancer, although therapeutically efficacious, is inefficient. A lack of understanding of the natural history of intraepithelial neoplasia has frustrated attempts to develop rational referral criteria, and it is only now that the appropriate trials are being undertaken. The development of outpatient investigative and therapeutic procedures has resulted in many more women being referred for investigation and treatment, with predictable pressure on other services offered by gynaecologists, but no demonstrable saving of life. Similar uncertainties surround a screening programme for colorectal cancer. The principal concerns are not about the efficacy of polypectomy in interrupting the polyp cancer sequence, although uncertainties about the frequency with which cancer arises de novo do require that the effectiveness of this intervention is formally tested. Our major concerns are with compliance, and the management of the individual who tests positive--that is, who is found to have a distal polyp. Technological advances and operator enthusiasm may, as has happened with the cervical screening programme, lead to a relaxation in the indications for further investigation and treatment. Such a development would affect resources substantially if a population screening programme were in place. Nevertheless, there are grounds for believing that a screening programme for colorectal cancer, using sigmoidoscopy, might be successful in certain age groups if compliance was satisfactory. The scale of benefits may be comparable with those achieved by the breast screening programme. Our limited cost analysis, which relates to only to specific items of clinical activity, suggest that the mean cost for each case of cancer prevented will be about 8000 pounds sterling. These conclusions suggest that screening by flexible sigmoidoscopy merits serious consideration. It is also imperative, however, that consideration should be given to resolving some of the uncertainties about the clinical management and surveillance of those found to have distal polyps.

Age Factors↗
PubMed1994

Constitutive expression of heat shock protein 90 (HSP90) in neurons of the rat brain.

Immunoblot analysis, immunocytochemistry and immuno-electron microscopy were employed to study the expression of HSP90 protein in the adult rat brain, using a specific polyclonal antiserum. Immunoblot analysis demonstrated equal levels of HSP90 in microdissected extracts from hippocampus, cortex, striatum and cerebellum. Immunocytochemistry and immuno-electron microscopy provided evidence that HSP90 is markedly expressed throughout all neuronal subpopulations of the CNS but not in non-neuronal cells except ependyma and choroid plexus. At the ultrastructural level, HSP90 immunoreactivity was predominantly found in perikarya but to a lesser extent also in dendrites and nuclei. The constitutive expression of HSP90 in widespread neuronal cell populations suggests a functional role in the physiological molecular program of CNS neurons.

Animals↗
PubMed1994

Hrp Mutants of Pseudomonas solanacearum as Potential Biocontrol Agents of Tomato Bacterial Wilt.

There have been many attempts to control bacterial wilt with antagonistic bacteria or spontaneous nonpathogenic mutants of Pseudomonas solanacearum that lack the ability to colonize the host, but they have met with limited success. Since a large gene cluster (hrp) is involved in the pathogenicity of P. solanacearum, we developed a biological control strategy using genetically engineered Hrp mutants of P. solanacearum. Three pathogenic strains collected in Guadeloupe (French West Indies) were rendered nonpathogenic by insertion of an omega-Km interposon within the hrp gene cluster of each strain. The resulting Hrp mutants were tested for their ability to control bacterial wilt in challenge inoculation experiments conducted either under growth chamber conditions or under greenhouse conditions in Guadeloupe. Compared with the colonization by a pathogenic strain which spread throughout the tomato plant, colonization by the mutants was restricted to the roots and the lower part of the stems. The mutants did not reach the fruit. Moreover, the presence of the mutants did not affect fruit production. When the plants were challenge inoculated with a pathogenic strain, the presence of Hrp mutants within the plants was correlated with a reduction in disease severity, although pathogenic bacteria colonized the stem tissue at a higher density than the nonpathogenic bacteria. Challenge inoculation experiments conducted under growth chamber conditions led, in some cases, to exclusion of the pathogenic strain from the aerial part of the plant, resulting in high protection rates. Furthermore, there was evidence that one of the pathogenic strains used for the challenge inoculations produced a bacteriocin that inhibited the in vitro growth of the nonpathogenic mutants.

Journal Article↗
PubMed1994

Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis.

The risk of developing colorectal cancer has been compared in two identically selected cohorts of patients with extensive Crohn's colitis (n = 125) and extensive ulcerative colitis (n = 486). In both groups the effects of selection bias have been reduced wherever possible. There was an 18-fold increase in the risk of developing colorectal cancer in extensive Crohn's colitis and a 19-fold increase in risk in extensive ulcerative colitis when compared with the general population, matched for age, sex, and years at risk. The absolute cumulative frequency of risk for developing colorectal cancer in extensive colitis was 8% at 22 years from onset of symptoms in the Crohn's disease group and 7% at 20 years from onset in the ulcerative colitis group. The relative risk of colorectal cancer was increased in both ulcerative colitis and Crohn's disease among those patients whose colitis started before the age of 25 years. Whether the absolute risk is greater in the younger age group or merely reflects that the expected number of carcinomas increases with age is uncertain. While there is an increased risk of developing colorectal cancer in extensive colitis the number of patients with Crohn's disease who actually develop colorectal cancer is small because many patients with extensive Crohn's colitis undergo colectomy early in the course of their disease to relieve persistent symptoms unresponsive to medical treatment.

Adolescent↗
PubMed1994

Crohn's disease and colorectal cancer.

The colorectal cancer risk in Crohn's disease eliminating all known biases was assessed in a cohort of 281 patients with Crohn's disease who resided in the West Midlands at the time of diagnosis, and were first seen within five years of onset of symptoms between 1945-1975. All patients were 15 years of age or more at onset and were followed up from 12-35 years (total 5213 person years at risk (PYR)). The colorectal cancer risk in the series compared with the risk in the general population was computed by applying sex and age specific PYRs to the date of death or end of the study period 31 December 1991. There were six colonic and two rectal cancers. Six of the eight colorectal cancers were diagnosed 20 or more years after the onset of Crohn's disease. The relative risk (RR) of colorectal cancer for the series as a whole was 3.4 (p < 0.001), with a fivefold excess in the colon, but no significant excess in the rectum. Patients with extensive colitis showed an 18-fold increase in risk (RR = 18.2, p < 0.001), which decreased with increasing age at onset. This study shows that there is a statistical excess risk of developing colorectal cancer in patients who develop their Crohn's disease at a young age of onset (less than 30 years of age).

Adolescent↗
PubMed1992

Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein.

A 93 kd polypeptide associated with the mammalian inhibitory glycine receptor (GlyR) is localized at central synapses and binds with high affinity to polymerized tubulin. This protein, named gephyrin (from the Greek gamma epsilon phi upsilon rho alpha, bridge), is thought to anchor the GlyR to subsynaptic microtubules. Here we report its primary structure deduced from cDNA and show that corresponding transcripts are found in all rat tissues examined. In brain, at least five different gephyrin mRNAs are generated by alternative splicing. Expression of gephyrin cDNAs in 293 kidney cells yields polypeptides reactive with a gephyrin-specific antibody, which coprecipitate with polymerized tubulin. Thus, gephyrin may define a novel type of microtubule-associated protein involved in membrane protein-cytoskeleton interactions.

Amino Acid Sequence↗
PubMed1991

The 93-kDa glycine receptor-associated protein binds to tubulin.

A peripheral membrane protein with a relative molecular mass of 93,000 Da is associated with cytoplasmic domains of the inhibitory glycine receptor of mammalian spinal cord. Here, evidence is given that this 93-kDa protein binds to polymerized tubulin. First, tubulin cofractionated with the 93-kDa protein upon affinity purification of the glycine receptor. Second, tubulin bound to the isolated 93-kDa protein in an overlay procedure. Third, in assays containing the purified glycine receptor, the 93-kDa protein as well as the glycine receptor alpha and beta subunits coassembled with tubulin and microtubules. The interaction of the 93-kDa protein with tubulin displayed high affinity (KD approximately 2.5 nM) and significant cooperativity (Hill coefficient approximately 2.1) and approached a stoichiometry of approximately 1:4 under saturating conditions. These data suggest that the 93-kDa protein anchors the glycine receptor at postsynaptic sites via binding to subsynaptic tubulin.

Animals↗
PubMed1991

Alternative splicing generates two variants of the alpha 1 subunit of the inhibitory glycine receptor.

The inhibitory glycine receptor (GlyR) in mammalian spinal cord displays pharmacological and molecular heterogeneity of its strychnine binding alpha subunit. Here, cDNAs were isolated which encode a variant (alpha ins 1) of the rat GlyR alpha 1 subunit that contains eight additional amino acids in its putative cytoplasmic domain. Analysis of the corresponding genomic sequence showed that alpha ins 1 transcripts result from alternative splice acceptor site selection. S1 nuclease protection experiments, Northern blot analysis, and RNA amplification by polymerase chain reaction revealed alpha 1 and alpha ins 1 mRNA in postnatal spinal cord, but not in other brain regions. Expression of synthetic alpha ins 1 RNA in Xenopus oocytes generated glycine-gated strychnine-sensitive chloride channels. These data indicate that alternative splicing contributes to GlyR alpha subunit heterogeneity in the mammalian central nervous system.

Amino Acid Sequence↗
PubMed1991

Survival of Dermatophilus congolensis in tropical clay soils submitted to different water potentials.

The survival of a rifampicin-resistant mutant of Dermatophilus congolensis in vertisol and oxisol soils from Guadeloupe and in their constitutive clays was studied using a pneumatic device for controlling water potentials (pF). Experiments were carried out at two pF values simulating the wet season and the dry season. Survival time depended on the type of soil and its water content. Organic matter had a protective effect on the microorganism in oxisol but not in vertisol. The pathogenicity of D. congolensis was preserved in the soils which could therefore act as temporary reservoirs of this pathogen. Long-term survival of this organism in soils mixed with water suggests that ponds and dipping tanks may constitute sources of infection for cattle.

Actinomycetales↗
PubMed1991

How to build a glycinergic postsynaptic membrane.

The inhibitory glycine receptor (GlyR) is a ligand-gated chloride channel protein found at many synapses of the mammalian central nervous system. During development, distinct isoforms of the GlyR are generated by the sequential expression of different alpha subunit variants. The appearance of adult-type GlyRs in spinal cord is accompanied by the accumulation of a 93 x 10(3) Mr receptor-associated peripheral membrane protein. The latter has been localized at the cytoplasmic face of glycinergic postsynaptic membranes and is thought to anchor GlyRs beneath glycinergic nerve terminals. The 93 x 10(3) Mr protein binds with high affinity to polymerized tubulin, suggesting that it functions as a receptor-microtubule linking component. Our data suggest that the interaction of developmentally regulated receptor isoforms with specialized microtubule-associated proteins represents a crucial step in the assembly of postsynaptic receptor matrices.

Animals↗