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Biomedical subjects

J Graham

Publications and source records attributed to J Graham.

At least 19 recordsLinked to original sources
PubMed1992

The effect of progestins on prolactin receptor gene transcription in human breast cancer cells.

The sex steroid hormone progesterone modulates the developmental and lactogenic activity of prolactin in the mammary gland. Regulation of the level of prolactin receptor (PRLR) provides one possible mechanism by which this may occur, prompting this investigation of the molecular mechanisms involved in progestin regulation of prolactin receptor levels. Treatment of T-47D and MCF-7 human breast cancer cells with 10 nM of the synthetic progestin ORG 2058 for 24 hr resulted in an increase in all four PRLR mRNA transcripts detected. The effect of ORG 2058 was shown in T-47D cells to be time- and concentration-dependent and resulted in an approximate two-fold increase in PRLR mRNA after 24 hr of treatment with 10 nM or 100 nM ORG 2058. Nuclear run-on assays indicated that ORG 2058 increased the rate of T-47D PRLR gene transcription at all times between 1 hr and 28 hr of treatment. The protein synthesis inhibitors cycloheximide and puromycin abrogated the induction of PRLR gene transcription at 1 hr and 2 hr, which demonstrated that on-going protein synthesis was required for the ORG 2058 effect and suggested that progestins may exert some transcriptional effects via the induction of an intermediary protein. These experiments demonstrated that progestin induced a transcriptionally based increase in PRLR gene expression and provided a mechanism by which progesterone may modulate the mitogenic activity of prolactin during mammary gland development.

Autoradiography↗
PubMed1992

A neural network chromosome classifier.

We present a chromosome classifier for automated karyotyping of banded chromosomes which uses a multi-layer perception neural network. Two network configurations have been investigated. The resulting classifiers have been trained and tested on data from three different data sets covering a range of data quality. Classification results compare very favourably with those obtained using a highly optimised parametric classifier.

Chromosomes↗
PubMed1992

Results of the multicenter evaluation of the CEDIA Phenytoin assay.

Thirteen clinical evaluation sites in Europe and U.S.A. investigated the CEDIA Phenytoin assay on Boehringer Mannheim/Hitachi analyzers with respect to imprecision, recovery of control sera, interlaboratory survey, linearity and method comparisons using patient samples. The linear dose-response relationship up to 40 micrograms/mL was confirmed by all participants. Imprecision at therapeutic analyte concentrations equalled that of other routine methods. Recovery of controls was found in a +/- 6% range for target values assigned by the CEDIA assay. The good interlaboratory transferability of the CEDIA assay was confirmed with control material and human samples. The reconstituted reagent can be used up to one month using weekly recalibration. In method comparison studies good correlations to other routine methods were obtained. Results in analyte-free human sera did not deviate systematically from the zero-point. Thus, the accuracy in patient sera has been shown for the CEDIA Phenytoin assay.

Dose-Response Relationship, Drug↗
PubMed1991

Direct transcriptional regulation of the progesterone receptor by retinoic acid diminishes progestin responsiveness in the breast cancer cell line T-47D.

Retinoic acid (RA) treatment of T-47D human breast cancer cells results in a rapid decrease in the concentration of progesterone receptor (PR) mRNA which causes a slow loss of cellular PR protein (Clarke, C. L., Roman, S. D., Graham, J., Koga, M., Sutherland, R. L. (1990) J. Biol. Chem. 265, 12694-12700). The mechanisms involved are unknown and this study was undertaken to determine whether the decline in PR mRNA was due to transcriptional inhibition and to evaluate the functional consequences of the RA-mediated decrease in PR. The transcription rate of the PR gene was decreased by RA, and the effect was maximal 2-3 h after treatment. Cycloheximide cotreatment was unable to relieve the inhibitory effect of RA and PR transcription suggesting that the effect was not dependent on ongoing protein synthesis. There was no effect of RA on PR mRNA half-life at the times examined (0-6 h of RA treatment). To determine the functional consequence of PR down-regulation the progestin-responsive plasmid pMSG-CAT was expressed transiently in T-47D cells which were then exposed to RA for 24 h. RA-pretreated cells were then treated with the synthetic progestin ORG 2058 and the extent of progestin stimulation of chloramphenicol acetyltransferase (CAT) activity measured. ORG 2058 treatment resulted in an induction of CAT activity which was maximal at a progestin concentration of 1 nM. Interestingly, the ability of ORG 2058 to induce CAT activity was decreased in RA-pretreated cells. The diminished progestin responsiveness of RA-pretreated cells was confirmed in separate experiments which showed that the progestin inducibility of TGF-alpha mRNA was also decreased in cells treated with ORG 2058 following pretreatment with RA for 24 h. These data demonstrate that RA decreases PR mRNA concentrations by direct transcriptional inhibition, leading to decreased cellular PR concentrations. The decreased levels of PR result in impaired responsiveness to progestins and this suggests that RA derived from dietary vitamin A may have a role in modulating cellular sensitivity to progestins.

Breast Neoplasms↗
PubMed1979

Subcortical projections of six visual cortical areas in the owl monkey, Aotus trivirgatus.

Subcortical projections of six visual cortical areas (Areas 17 and 18, the Middle Temporal, Dorsomedial and Medial Areas, and the Posterior Parietal Region) in the owl monkey, Aotus trivigatus, were investigated with autoradiographic methods following injections of tritiated proline. No contralateral projections were demonstrated. While some brainstem structures received input from all six subdivisions of cortex, each cortical area appeared to exhibit its own unique pattern of subcortical projections. All six cortical areas were found to project to the superior and inferior divisions of the pulvinar, reticular nucleus of the thalamus, pretectum and superior colliculus. Other subcortical targets of one or more visual cortical areas were the basal ganglia, claustrum, zona incerta, one or more of the intralaminar nuclei, lateral posterior nucleus, pregeniculate nucleus, dorsal lateral geniculate nucleus, and pontine nuclei. Furthermore, details of corticofugal projections to the dorsal lateral geniculate nucleus, pretectum and superior colliculus varied with the cortical area studied. The projections to the reticular nucleus, pregeniculate nucleus, dorsal lateral geniculate nucleus, the inferior and a portion of the superior division of the pulvinar and the superior colliculus were found to be topographically organized. The targets of the subcortical projections were compared with those of the retina, as revealed by autoradiographic methods following tritiated proline injections of the eye and were found to overlap to varying extents in the superior colliculus, pretectum and dorsal lateral geniculate nucleus and to be segregated in the pregeniculate nucleus. The results substantiate the validity of previous studies in the owl monkey that suggest that the visual cortex is subdivided into several functionally distinct areas; and illustrate the complexity of corticofugal influence on visual processing.

Animals↗
PubMed1979

Thalamic relay nuclei for cerebellar and certain related fiber systems in the cat.

Anterograde labeling techniques were used to define the terminal distributions in the thalamus of afferents arising in the deep cerebellar nuclei, entopeduncular nucleus and substantia nigra. Anterograde and retrograde labeling methods were then used to determine the extent of the cortical projections of the cerebellar relay nuclei. The cerebellar projection to the contralateral ventral nuclei of the thalamus terminates in a zone which is separate from that receiving pallido- and nigrothalamic fibers. None of the zones of termination of these fiber systems corresponds to commonly recognized cytoarchitectonic divisions. Instead, they include parts of the ventroanterior (VA), ventrolateral (VL) and principal ventromedial (VMp) nuclei. Some cells within the zone of termination of cerebellar afferents project to parietal cortex (areas 5 and 7). A further, distinct group of cells in this zone projects to motor cortex (area 4). But projections to area 4 also arise from small groups of cells: (a) in the zone receiving nigro- and pallidothalamic fibers; (b) in the part of VL, distinct from the cerebellar terminal zone, in which spinothalamic fibers terminate. Cerebellar, nigral, and entopeduncular fibers also terminate in the intralaminar nuclei. These projections are far greater in extent than those arising in the spinal cord. Some parts of the intralaminar nuclei are dominated by a particular afferent system, while others show substantial overlap of the terminal zone of several afferent systems.

Animals↗
PubMed1979

Binding of oligonucleotides to the disk of tobacco-mosaic-virus protein.

The trinucleoside diphosphate A-A-G and the hexanucleotide fraction from a ribonuclease I digest of yeast RNA have been soaked into crystals of the disk aggregate of tobacco mosaic virus protein. At high concentrations these cause disruption of the crystal, probably by mimicking the normal nucleation of assembly. At lower nucleotide concentrations the crystals remain intact and the differences caused by nucleotide binding have been studied by X-ray diffraction. The most obvious change is an upwards movement of about 0.3 nm at the low-radius end of the left radial helix in the protein with some stiffening of the helix so that it now extends visibly in from 4 nm to 6 nm radius. Similar shifts also occur in the right radial and left slewed helices. A positive peak, which is tentatively identified with the bound oligonucleotide, is seen around 4 nm radius and below the right radial helix. The amino acid residues in possible contact with this feature are discussed.

Nucleic Acid Conformation↗
PubMed1979

Cortical projections of the medial visual area in the owl monkey, Aotus trivirgatus.

The cortical projections of the Medial Area (M) of the owl monkey were studied using the autoradiographic method. Area M projects to several extrastriate areas, including Area 18, in a pattern of terminations unlike that which would be expected if M was part of a larger Area 19 or V III band. The pattern of terminal lamination was found to be somewhat unusual in that projections were to layers VI, I and the deep portion of layer V in the major target areas.

Animals↗
PubMed1978

The fibrinogen uptake test after hip surgery.

The fibrinogen uptake test has been used to detect deep vein thrombosis after total hip replacement in 90 patients. The upper third of the thigh in each leg was ignored and peripheral leg counting carried out distal to this. The results were directly compared with the findings of venography in the 170 legs of the 90 patients. There was a high false positive rate (30 per cent) with the fibrinogen uptake test which was associated with the presence of the knee joint effusion or varicose veins, but not with the site of operation. There was a low false negative rate (less than 5 per cent), and the fibrinogen uptake test, used in this way, may fail to detect a percentage of small thrombi in the wound area that are probably produced by the local trauma of operation. It is considered that the fibrinogen uptake test has a clinical use as a screening test for deep vein thrombosis after hip replacement, but venography is required in the interests of accuracy.

Arthroplasty↗
PubMed1978

An unusual case of metastatic carcinoma to the eyelid.

A 46-year-old woman developed a painless nodular lesion of her right lower eyelid four years after having a right radical mastectomy for breast carcinoma. The lesion slowly increased in size over one year to involve full thickness eyelid tissue that included the margin and inferior punctum and was associated with localized loss of cilia. The clinical appearance of the lesion and its course of development suggested a primary eyelid neoplasm. Incisional biopsy revealed metastatic mammary carcinoma.

Breast Neoplasms↗
PubMed1978

Palliative urinary diversion for malignant ureteral obstruction.

An analysis of 62 palliative urinary diversions for malignant ureteral obstruction is presented. The average postoperative survival was 187 days. Cell type, duration of known disease, tumor grade and stage, renal function and previous therapy did not strongly influence survival. Renal function returned to normal in 64 per cent of the azotemic patients. Morbidity and mortality rates were high, largely because of underlying disease and adjuvant therapy . Nearly two-thirds of the patients left the hospital and this group subsequently spent 84 per cent of their remaining survival time at home. A criterion is presented for patient selection and suggestions are made for the selection of an operative procedure.

Abdominal Neoplasms↗
PubMed1978

Cholesterol granuloma of the maxillary antrum.

Five cases of cholesterol granuloma in the maxillary antrum are described. The lesion takes place in the mucosa. It seems likely that filtration and haemorrhage are the 2 main ways in which cholesterol is concentrated in certain tissues. The maxillary antrum provides a clear illustration of these 2 mechanisms at work.

Adult↗
PubMed1978

Location of tyrosine residues in the disk of tobacco-mosaic-virus protein and comparison of the subunit packing with that of the virus.

The products of iodination of the disk of tobacco mosaic virus coat protein have been investigated in order to locate the reactive amino acid residues in the three-dimensional structure. Reaction occurs mainly with tyrosine-139 and, to a lesser extent, tyrosine-2 and the positions of these modified residues have been determined by X-ray crystallography. Different extents of reaction are found in the two rings of the disk and also, on adding the high salt concentration needed for stabilisation of the crystal during reaction, some conformational changes in the polypeptide chain in the inner part of the disk. Comparison of the relative positions of residues 27 and 139 in the disk and virus shows that little distortion occurs in the outer part of the subunit during the transition between the disk and virus structures.

Amino Acids↗
PubMed1978

Problems in family practice. Rectal bleeding.

The diagnosis and management of rectal bleeding problems varies with the urgency of the situation, the age of the patient, and the applicability of available diagnostic methods. Every instance of rectal bleeding is a problem that demands investigation by endoscopic, radiographic, and laboratory means. A physician can be misled by the patient's understatement or underobservance of bleeding. A good history obtained as quickly as possible in urgent circumstances and in great detail under more relaxed circumstances is of immeasurable diagnostic value.

Adult↗
PubMed1978

Proposed coupling of chromatin replication, hormone action, and cell differentiation.

DNA replication in isolated nuclei is highly dependent on the availability of soluble proteins from the cell cytoplasm. Activity is distributed nonrandomly among the different proteins, and the range of proteins that are required for optimal DNA replication varies with the fractions of DNA being replicated. Support of DNA replication has been correlated with the uptake of these proteins by nuclei and their integration into an immature form of the newly replicated chromatin; the latter has been shown by density analysis to be richer in protein content than the bulk of nonreplicating chromatin. Pulse labeling of DNA in living cells has revealed that a similar protein-rich chromatin is formed as an intermediate in chromatin replication in vivo; however, this form rapidly matures by the exclusion of proteins. The dependency of DNA replication on the presence of soluble cytoplasmic proteins and the physical association of these entities with newly replicated chromatin prompt the proposal that availability of specific proteins may play an important role in determining the ultimate genetic expressability of the matured chromatin and thus the cell phenotype. The finding that dexamethasone, a steroid that regulates the expression of several genes and directs the differentiation of certain cells, can modify the uptake of proteins in isolated nuclei is in accord with this hypothesis.

Cell Differentiation↗