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Biomedical subjects

D Lane

Publications and source records attributed to D Lane.

At least 37 records · Page 2Linked to original sources
PubMed1991

Expression of RB and p53 proteins in HPV-positive and HPV-negative cervical carcinoma cell lines.

Mutations within the tumor suppressor genes Rb-1 and p53 are commonly found in many human malignancies, and loss of wild-type function of both p53 and RB appear to be important events in the development of these malignancies. Interference with normal RB and p53 function in the cell has apparently also been exploited by the oncogenic genital human papillomaviruses (HPVs), which encode transforming proteins capable of binding cellular RB and p53 proteins. We have investigated the expression of RB and p53 in a series of eight cervical carcinoma cell lines, six of which contain HPV sequences and two of which have arisen apparently independently of HPV infection. In the six HPV-positive lines, no evidence of abnormal RB or p53 protein could be detected. However, there was evidence for abnormal RB and p53 in the two HPV-negative lines. These data are consistent with the hypothesis that loss of wild-type RB and p53 function is necessary for tumor development and that such loss can occur either by mutation within the cellular gene or by expression of viral proteins capable of complexing wild-type cellular proteins.

Carcinoma↗
PubMed1991

Asthma: a diagnostic and therapeutic challenge.

Asthma is a disease needing urgent action. Morbidity and mortality are rising, despite advances in our understanding of asthma and in its treatment. The lifetime prevalence of asthma in children varies from 5 to 31%, depending on the defining criteria, and even when recent prevalence (occurring in the past two years) is examined, rates from 5 to 18% have been found. There is growing evidence which shows that signs of reversible airways disease occur in the elderly with even greater frequency and it is likely that at least 10% of the population will need asthma treatment at some stage of their lives; this means that well over five million people in the UK or 250 patients in each 'average' general practice list of 2500 merit the diagnosis of asthma at some stage of their lives. The fact that an average practice is likely to have diagnosed less than half that number clearly implies that asthma is first and foremost an under-diagnosed disease.

Asthma↗
PubMed1991

Mutant p53, EGF receptor and c-erbB-2 expression in human breast cancer.

p53 expression was studied in 111 primary breast cancers with a monoclonal antibody (PAb240) that reacts with an epitope in mutant p53. Epidermal growth factor receptors (EGFr) and oestrogen receptors (ER) measured by ligand binding, c-erbB-2 expression assessed by immunochemistry and lymph node status were compared with p53 staining. Fifty-nine tumours (53%) were positive for p53, and this correlated with EGFr expression (P less than 0.02), which is a known poor prognostic factor. Eighteen out of 59 p53+ tumours expressed c-erbB-2 versus 4 out of 52 p53- tumours assessed on paraffin sections. However, assessing c-erbB-2 by Southern blotting and immunochemistry on frozen sections showed that 20 out of 59 p53+ tumours overexpressed or had amplified c-erbB-2 compared with 15 out of 52 p53- tumours (not significant). Mean EGFr concentration in p53+ tumours was 31 fmol per mg of membrane protein versus 14 fmol mg-1 in p53- tumours. Cytoplasmic staining was the most frequent pattern found for p53, but some cases showed cytoplasmic plus nuclear staining, or focal cells with predominantly nuclear staining. Thus, abnormal p53 is the commonest oncogene abnormality described in breast cancer. The association with EGFr expression suggests that these oncogenes interact in the pathogenesis of breast cancer.

Biomarkers, Tumor↗
PubMed1990

Increased expression of mutant forms of p53 oncogene in primary lung cancer.

Primary lung cancer samples of the major histological types were examined for expression of the tumor suppressor gene p53 by immunohistochemistry. Abnormalities in p53 expression were found in 28 of 40 carcinomas, 14 of 17 squamous tumours showing abnormal p53 expression, whereas no expression of p53 was detectable in 7 carcinoid tumours or in 10 normal lung samples. Direct evidence for homozygous expression of mutant p53 mRNA in representative carcinomas was obtained by means of an asymmetric polymerase chain reaction mRNA sequencing strategy, which allowed sequencing without any cloning step. All the mutations were G to T transversions resulting in mis-sense mutations in aminoacids highly conserved in evolution. Mutation of the p53 gene is the most frequently identified genetic change in human lung cancer; these findings suggest that simple immunohistological methods can provide strong evidence of such mutation.

Adenocarcinoma↗
PubMed1989

Autoregulation of the ccd operon in the F plasmid.

Mini-F sequences, including the promoter and portions of the ccd region, were inserted upstream of lacZ in promoterless lacZ vectors, and beta-galactosidase specific activities were measured. The results showed that the H (ccdA), G (ccdB) and D genes, together with a promoter, comprise an operon. Ccd operon expression was shown to be regulated at the level of transcription by the G gene product, probably in concert with the H gene product. Thus expression is autoregulated. Expression of the D gene was largely dependent on the ccd promoter, although low levels of transcription from another promoter within the ccd coding region were detected.

Escherichia coli↗
PubMed1988

Mapping and regulation of the pifC promoter of the F plasmid.

The pif region of the F plasmid, which causes abortive infection of Escherichia coli by T7 bacteriophage, is autogenously controlled by the product of the pifC gene. Here we describe the identification of the pif operon promoter by S1-nuclease mapping, and show that it is autoregulated at the transcriptional level and that its activity is modulated by integration host factor.

Bacterial Proteins↗
PubMed1988

A replication region of the IncHI plasmid, R27, is highly homologous with the RepFIA replicon of F.

A region of the IncHI plasmid R27 has been found to share very close nucleotide sequence homology with the RepFIA replicon of F. This region has been located on a 1.6 kb segment of R27 plasmid DNA, and corresponds to ori-2 and the E gene of F. The incC repeat sequence region shows reduced homology, with the F repeats being an imperfect subset of a larger repeated sequence found in R27. The E gene homologue of R27 is able to initiate replication from the F ori-2 sequence and to repress the E gene promoter of F. The results are consistent with the observed incompatibility behaviour of R27, and have a bearing on the specificity of interaction of E protein with its DNA-binding sites.

Amino Acid Sequence↗
PubMed1987

Coordinate expression of the endogenous p53 gene in beta cells of transgenic mice expressing hybrid insulin-SV40 T antigen genes.

The expression of p53 has been evaluated during oncogenesis of the pancreatic beta cells in transgenic mice harboring hybrid insulin-SV40 T antigen genes. Significant levels of p53 are detected in all cells expressing large T antigen. In contrast, the protein is undetectable in normal beta cells. There is a complete correspondence between the onset of expression of T antigen and the appearance of the endogenous p53 protein. In tumors, the two proteins are found in a complex. In addition, free uncomplexed T antigen is detected in every cell which expresses the transgene. These results are consistent with the participation of p53 in T antigen-induced tumorigenesis in vivo. The early appearance of p53 in all beta cells expressing large T cannot readily explain the progression of a small fraction of these cells into solid tumors.

Animals↗
PubMed1987

Analysis of the F plasmid centromere.

The nucleotide sequence of the cis-acting partition site (centromere) of the miniF plasmid has been determined. Its most notable feature is a reiterated 43 base pair unit. A series of plasmids deleted for portions of the repeat region was constructed and tested for incompatibility with R386 and for stability of inheritance. The extent of incompatibility with R386 was correlated with the number of repeat units. In contrast, the great majority of the repeats were not needed for miniF stability. An adjacent region of unique sequence was also found to be involved in centromere function.

Base Sequence↗
PubMed1987

Cytotoxicity of respirable dusts from industrial minerals: comparison of two naturally occurring and two man-made silicates.

The membranolytic and cytotoxic properties of two naturally occurring (chrysotile asbestos; attapulgite clay) and two man-made (Fiberfrax, an aluminium-silicate, and xonotlite, a calcium silicate) industrial minerals were compared. "Short" fiber fractions of chrysotile and Fiberfrax were obtained by sedimentation in demineralized water, while the attapulgite and xonotlite samples were used as obtained. The aluminium silicate fibers were found to be non- hemolytic, while for the other three silicates, chrysotile had the strongest hemolysis potential, followed very closely by xonotlite; attapulgite was less hemolytic than the former two silicates, but was nevertheless highly hemolytic to the rat erythrocytes. Using rat pulmonary alveolar macrophages, the in vitro cytotoxicity assays showed that with fresh cell monolayers, all four silicates were equivalent in causing cell damages at a dose of 250 micrograms; at a lower dose (50 micrograms), the intensity of the cytotoxic effect was in the decreasing order: Fiberfrax greater than attapulgite greater than chrysotile greater than xonotlite. With one day-old cultured cell monolayers, a dose of 250 micrograms of the silicates fibers was less cytotoxic, with the exception of the attapulgite fibers which remained essentially as cytotoxic as with the fresh cell monolayers. The reduced cytotoxic response was especially noticeable with the chrysotile fibers. At 50 micrograms, the cytotoxicity scale of the mineral dusts with one day-old cell monolayers was essentially the same as the one obtained with the fresh cell monolayers, that is: Fiberfrax approximately equal to attapulgite greater than chrysotile greater than or equal to xonotlite. Overall, these in vitro tests imply: 1) that all four industrial silicates tested can be considered to be "biologically active"; 2) that on the basis of their different reactivities with the two types of cell culture conditions used, their biological reactivity in vivo might be quite distinct. This might be especially true for at least the chrysotile, attapulgite and xonotlite short fibers, considering that these three types of silicate dusts have very similar dimensions. Moreover, for the chrysotile and attapulgite samples, fiber numbers is probably not an important factor, since the density of the two silicates is roughly the same. The unaltered cytotoxic responses of the American attapulgite fibers in the two macrophage assays correlate well with the fact that short attapulgite fibers seems to have a stronger in vivo reactivity than short chrysotile fibers. In fact, it might be the strongest of the four industrial silicates tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Somatosensory evoked potentials from dermatomal stimulation as an indicator of L5 and S1 radiculopathy.

Dermatomal somatosensory evoked potential (DSEP) results for L5 and S1 were contrasted with electromyography (EMG) results for 50 patients referred to the electrodiagnosis laboratory to document the presence of radiculopathy. Stimulation sites were over the dorsum of the foot at the distal fifth metatarsal for the S1 dermatome and at the web space of the first and second toe for the L5 dermatome. Recordings were made at PZ reference to FZ. Spinal cord or cauda responses could not be detected. Both EMG and DSEP were contrasted to myelography or lumbar computerized tomography results on 31 patients. Side-to-side amplitude differences proved too variable to be of use. Sixty-five percent of abnormal DSEP results were on the basis of side-to-side latency criterion, and 35% were on the basis of an absent unilateral response. When compared to EMG and anatomic studies DSEP showed less accuracy and sensitivity. The specificity of the two tests was similar. Using both positive EMG and anatomic studies to define radiculopathy, there were 27% false negative tests and 9% false positive tests. An 86% root level correlation was found between EMG and DSEP. Dermatomal somatosensory evoked potential studies add little to the diagnosis of radiculopathy.

Adult↗
PubMed1987

Forecasting client transitions in British Columbia's Long-Term Care Program.

This article presents a model for the annual transitions of clients through various home and facility placements in a long-term care program. The model, an application of Markov chain analysis, is developed, tested, and applied to over 9,000 clients (N = 9,483) in British Columbia's Long Term Care Program (LTC) over the period 1978-1983. Results show that the model gives accurate forecasts of the progress of groups of clients from state to state in the long-term care system from time of admission until eventual death. Statistical methods are used to test the modeling hypothesis that clients' year-over-year transitions occur in constant proportions from state to state within the long-term care system. Tests are carried out by examining actual year-over-year transitions of each year's new admission cohort (1978-1983). Various subsets of the available data are analyzed and, after accounting for clear differences among annual cohorts, the most acceptable model of the actual client transition data occurred when clients were separated into male and female groups, i.e., the transition behavior of each group is describable by a different Markov model. To validate the model, we develop model estimates for the numbers of existing clients in each state of the long-term care system for the period (1981-1983) for which actual data are available. When these estimates are compared with the actual data, total weighted absolute deviations do not exceed 10 percent of actuals. Finally, we use the properties of the Markov chain probability transition matrix and simulation methods to develop three-year forecasts with prediction intervals for the distribution of the existing total clients into each state of the system. The tests, forecasts, and Markov model supplemental information are contained in a mechanized procedure suitable for a microcomputer. The procedure provides a powerful, efficient tool for decision makers planning facilities and services in response to the needs of long-term care clients.

Aged↗