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Biomedical subjects

J Bell

Publications and source records attributed to J Bell.

At least 181 records · Page 10Linked to original sources
PubMed1994

Neuropathological phenotype and 'prion protein' genotype correlation in sporadic Creutzfeldt-Jakob disease.

A systematic study of 'prion protein' genotype in cases of sporadic Creutzfeldt-Jakob disease showing amyloid plaques staining with anti-prion protein antibody has been performed. This revealed a relative excess of cases with valine at position 129 of the gene's open reading frame. The observation emphasises the importance of this site of common polymorphism in influencing the neuropathological phenotype in human spongiform encephalopathy.

Aged↗
PubMed1994

The observation of angiogenin and basic fibroblast growth factor gene expression in human colonic adenocarcinomas, gastric adenocarcinomas, and hepatocellular carcinomas.

Using digoxigenin-labelled, synthetic oligonucleotide probe cocktails of angiogenin and bFGF genes, the expression of the two genes was observed by in situ hybridization in ten colonic adenocarcinomas, seven gastric adenocarcinomas, and four hepatocellular carcinomas. The angiogenin gene was expressed in eight of the ten cases of colonic adenocarcinoma and in all of the four cases where dysplastic glands were found. Angiogenin expression was evident in four of the seven cases of gastric adenocarcinoma. bFGF expression was detected in only five of the seven gastric carcinoma cases. The mRNAs for angiogenin and bFGF were mainly cytoplasmic in distribution and were only occasionally seen in the nuclei of the positive cells. Neither the angiogenin gene mRNA nor the bFGF mRNA was expressed in the four cases of hepatocellular carcinoma. It is postulated that the angiogenin gene may play an important role in angiogenesis in colonic adenocarcinomas; in gastric cancers, both angiogenin and bFGF were involved in this process. For hepatocellular carcinomas, neither angiogenin nor bFGF production appeared to be related to angiogenesis.

Adenocarcinoma↗
PubMed1994

A note on modeling mechano-chemical transduction with an application to a skin receptor.

Strain-sensitive (also called stretch-sensitive) ionic channels are thought to be present in various mechanoreceptors. The gating of these channels is precipitated by mechanical strains, as opposed to the usual activation processes of changes in membrane potential or other ligands. Below we present a class of models for the strain-activated mechanism, compare our approach to one of Sachs and Lecar (1991) and apply the gating mechanism to a model of a specific mechanoreceptor, namely a Pacinian corpuscle neurite model. The simulation experiment suggests the activation energy of the channel depends linearly, rather than nonlinearly, on the (hoop) strain in the receptor membrane.

Animals↗
PubMed1994

Creutzfeldt-Jakob disease and cerebral amyloid angiopathy.

An 83-year-old female with no personal or familial neurological history developed progressive gait and speech disturbance and left motor deficit. She suffered intractable seizures and died 3 months after the onset of neurological signs. Neuropathology showed severe spongiosis and gliosis in the cortex and basal ganglia, and diffuse cerebral amyloid angiopathy. Immunostaining for prion protein (PrP) showed intense PrP positivity in areas of confluent spongiosis and some granular staining in astrocytes. The cortical vessel walls stained positively for beta/A4 amyloid but not for PrP amyloid. Both types of amyloid were only observed in pericapillary parenchyma, in areas with severe spongiosis. There were only a few tangles and neuritic plaques in the temporal cortex; amyloid plaques were not present either by silver stains or immunostains. There was neither arteriopathic leukoencephalopathy nor cerebral hemorrhage. Immunoblot analysis of brain extracts revealed an abnormal proteinase K-resistant isoform of PrP. Association of Creutzfeldt-Jakob disease and Cerebral amyloid angiopathy in the absence of Alzheimer changes in unusual. The association of PrP and beta/A4 amyloid deposits could have been fortuitous in an 83-year-old patient. An etiopathogenic relationship between beta/A4 amyloid deposition and PrP accumulation may also be considered.

Aged↗
PubMed1994

Study of propagation along nonuniform excitable fibers.

Two related reaction diffusion systems that support traveling wave solutions when parameters are constant are studied when there are jump discontinuities in the diffusion coefficient. The first system represents a classical axon model where the fiber had a jump in diameter at discrete locations and the membrane dynamics represent those of barnacle muscle (which we call Morris-Lecar dynamics). The second model represents a passive cable with a uniform density of spines that have Morris-Lecar dynamics. Conditions under which echo waves form are studied, as well as conditions when wave blocking takes place with a thickening of the fiber.

Action Potentials↗
PubMed1994

Mortality and cancer incidence following radiotherapy for seminoma of the testis.

From the records of the Thames Cancer Registry, 859 patients were identified, who were treated with radiotherapy for seminoma of the testis between 1961 and 1985. Second cancer incidence and mortality and also causes of non-cancer deaths in the study population were examined. Fifty-one (6%) patients died of testicular cancer, 42 within 5 years of diagnosis. There were 42 second cancers (other than second testicular cancers), and 20 deaths from second cancer (expected, 22.1--non-significant). The only subtype of cancer with a notable excess was leukaemia (4 incident cases observed; 0.64 expected; relative risk 6.2, 95% C.I., 2.7-14.8, 95% C.I., 2.7-14.7). The overall death rate from causes other than testicular cancer was not elevated (82 observed, 82.06 expected). There was some suggestion of an increase in the risk of mortality with time; for 10 or more years after treatment the relative risk was 1.31 (95% C.I., 0.95-1.81). There was no evidence of excess non-cancer deaths (62 observed, 60 expected). We conclude that there is no definite evidence from this investigation of increased risk of mortality secondary to radiotherapy; however, the excess incidence of leukaemia may be treatment-related and the cohort will be followed further.

Adolescent↗
PubMed1994

Effects of 4-hydroxytamoxifen and a novel pure antioestrogen (ICI 182780) on the clonogenic growth of human breast cancer cells in vitro.

We have investigated the effects on breast cancer cell growth of 4-hydroxytamoxifen (4OHT), a conventional antioestrogen with agonist activity, and 7 alpha-[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra- 1,3,5,(10)- triene-3,17 beta-diol (ICI 182780), a novel, pure antioestrogen, using established human breast cancer cell lines and cancer cells obtained directly from breast cancer patients with malignant pleural effusions who had relapsed on tamoxifen. The effects of the two agents were assessed using the Courtenay-Mills clonogenic assay, which measures the growth of single cancer cells as colonies suspended in soft agar. The standard assay was modified by the use of defined serum- and phenol red-free growth medium. The growth of oestrogen receptor (ER)-positive MCF-7 cells in the assay was oestrogen responsive. Both antioestrogens inhibited the stimulatory effects of 1 nM oestradiol, but ICI 182780 caused significantly greater inhibition than 4OHT at 0.1-1.0 microM concentrations. In the absence of oestradiol, 4OHT but not ICI 182780 caused significant stimulation of colony formation at low (0.01-1.00 nM) concentrations. Neither antioestrogen had any effects on colony formation by the ER-negative Hs578T cell line. Successful colony formation was obtained in primary cultures from six out of eight malignant effusions. Colony formation was significantly stimulated by 0.1 nM oestradiol in four cases and by 10 nM 40HT in two cases. In contrast, ICI 182780 exhibited no intrinsic stimulatory activity and significantly inhibited both oestradiol- and 4OHT-stimulated cell growth. We conclude that the agonist activity of 4OHT and other conventional antioestrogens may cause treatment failure in some patients by stimulating breast cancer cell growth. The new, pure antioestrogen ICI 182780 is a more potent oestrogen antagonist than 4OHT and exhibits no growth-stimulatory activity. This agent may therefore offer therapeutic advantages over conventional antioestrogens in patients with advanced breast cancer and may be effective after conventional agents have failed.

Adult↗
PubMed1994

Incompleteness of oral cancer registration in south-east England, 1971-87.

Our objective was to examine the accuracy of reporting oral cancer cases to the cancer registry system. We examined a series of 583 patients with oral malignancies treated at several institutions and reported by our laboratory during 1971-87. Using patient details and pathology diagnosis, we traced the entries for these patients in the Thames Cancer Registry (TCR). Of the 583 patients identified 351 were eligible for entry in TCR. Of these, 255 were traced in the Registry and 96 were not (27%). The data, when separated for the period 1971-80 and post-1980, showed that for the earlier period under-reporting was 21% and for the later period 36%: Underascertainment was particularly marked in the mid-1980s while regional registration in the North Thames Regions was being discontinued and taken over by TCR. The major factors contributing to under-reporting are thought to be the fact that many specialised dental units and oral pathology laboratories may fail to be included in the cancer registration process and possible inconsistencies in death-initiated registrations related to this site. Similar levels of under-reporting were observed in another regional registry (South Western), suggesting that this may be a national problem. If this is the case, national incidence rates for mouth cancer may have been underestimated by about 25% during this period. This contrasts with over 90% completeness of registration for cancers as a whole.

Age Factors↗
PubMed1994

A radiation hybrid map of 506 STS markers spanning human chromosome 11.

We present a high resolution radiation hybrid map of human chromosome 11 using 506 sequence tagged sites (STSs) scored on a panel of 86 radiation hybrids. The 506 STSs fall into 299 unique positions (average resolution of about 480 kilobases (kb)) that span the whole chromosome. A subset of 260 STSs (143 positions) form a framework map that has a resolution of approximately 1 megabase between adjacent positions and is ordered with odds of at least 1,000:1. The centromere was clearly defined with pericentric markers unambiguously assigned to the short or long arm. The map contains most genes (125) and expressed sequence tags (26) currently assigned to chromosome 11 and more than half of the STSs are polymorphic microsatellite loci. These markers and the map can be used for high resolution physical and genetic mapping.

Animals↗
PubMed1994

Propofol and fentanyl anaesthesia for patients with low cardiac output state undergoing cardiac surgery: comparison with high-dose fentanyl anaesthesia.

We have compared the haemodynamic effects of an infusion of propofol 8 mg kg-1 h-1 followed by 4 mg kg-1 h-1 and fentanyl 15 micrograms kg-1 (group 1) with midazolam 3-6 mg and fentanyl 60 micrograms kg-1 (group 2) in patients with a low cardiac output state undergoing cardiac surgery. Heart rate was lower in group 1 throughout the period before cardiopulmonary bypass. There were no significant differences between the groups in other measured variables. Arterial pressure decreased in both groups after induction, by 21% in group 1 and 18% in group 2. Thermodilution assessment of right ventricular ejection fraction was unchanged. Myocardial contractility was not affected adversely. Patients in group 1 who received an infusion of propofol and a smaller dose of fentanyl awakened sooner and the trachea was extubated earlier.

Adult↗
PubMed1994

The effect of intake procedures on performance in methadone maintenance.

The effect of assessment and intake procedures on the outcome of methadone maintenance treatment was investigated in a natural experiment in which a single methadone clinic admitted 89 patients by a rapid intake procedure, and 74 patients who had been on a waiting list and underwent formal assessment interviews. Outcome measures were frequency of illicit drug use as detected by urine tests, and risk of dropping out or being expelled from treatment. Subjects admitted after prolonged, formal assessment were more likely to be expelled, and were more than twice as likely to leave during the first 400 days of maintenance treatment (95% Cl relative risk 1.1 to 5.2). The odds of formally assessed subjects using heroin in the first 6 months of treatment were twice those of the rapid intake group (95% Cl odds ratio 1.5 to 2.2). The formal assessment process deterred half the initial applicants, yet seems to have either selected individuals with a worse prognosis or to have had a negative effect on in-treatment performance.

Female↗
PubMed1994

Diversity of the P2 protein among nontypeable Haemophilus influenzae isolates.

The genes for outer membrane protein P2 of four nontypeable Haemophilus influenzae strains were cloned and sequenced. The derived amino acid sequences were compared with the outer membrane protein P2 sequence from H. influenzae type b MinnA and the sequences of P2 from three additional nontypeable H. influenzae strains. The sequences were 76 to 94% identical. The sequences had regions with considerable variability separated by regions which were highly conserved. The variable regions mapped to putative surface-exposed loops of the protein.

Amino Acid Sequence↗