PubMed Health⌕ Search

Biomedical subjects

J Telford

Publications and source records attributed to J Telford.

At least 37 records · Page 2Linked to original sources
PubMed1994

Clozapine effects on glucose metabolic rate in striatum and frontal cortex.

Eighteen patients with schizophrenia had cerebral metabolic rates assessed with positron emission tomography during a double-blind, placebo-controlled crossover study of clozapine treatment. Relative metabolic rates were increased in the basal ganglia, especially on the right side. In the frontal lobe, metabolic rates were lowered, more on the left than on the right. The anterior nuclei of the thalamus also showed lower metabolic rates after clozapine. We have previously observed patients with schizophrenia to have low metabolic rates in the basal ganglia and to lack the normal right > left asymmetry; in this study, clozapine normalized striatal activity. In the frontal lobe, asymmetry was normalized, but hypofrontal function was, if anything, exaggerated. This effect in the frontal lobe was not observed with haloperidol in earlier studies. The cortical effects of clozapine may be related to its unique clinical properties and suggest important differences between typical and atypical antipsychotic drugs.

Adult↗
PubMed1992

Intraepithelial airway dendritic cells: a distinct subset of pulmonary dendritic cells obtained by microdissection.

Dendritic cells (DC), in general, and pulmonary DC, in particular, are a heterogeneous population of cells, their phenotype and function being dependent on their anatomic location, their state of activation, and the regulatory effect of locally secreted cytokines. Using a novel microdissection technique, the epithelium from the trachea and entire airway system was harvested, and the contained DC isolated at greater than 90% purity. The phenotype and function of these airway DC (ADC) was compared to DC isolated, at greater than 90% purity, from the parenchyma of the same lung. In contrast to lung DC (LDC), ADC did not express intercellular adhesion molecule 1 (ICAM-1) in situ, the amount of immune associated antigen (Ia) expressed was less (as determined by immunoperoxidase staining and immunopanning), and greater than 50% of ADC displayed Fc receptors (FcR). The majority of LDC were ICAM-1+, less than 5% expressed FcR, and all were intensely Ia+. Airway DC were most numerous in tracheal epithelium, but they were also present in small numbers in the epithelium of the most distal airways. Their numbers increased in all segments of the tracheobronchial epithelium in response to the administration of IFN-gamma. ADC were consistently more effective than LDC in presenting soluble (hen egg lysozyme) and particulate (heat-killed Listeria monocytogenes) antigens to antigen-sensitized T cells. By contrast, LDC were significantly more efficient in stimulating the proliferation of nonsensitized T cells in an autologous mixed leukocyte reaction. These data suggest that in normal animals, intraepithelial DC of airways share many attributes with Langerhans cells of the skin. Interstitial LDC, by contrast, reside in an environment where they may be exposed to a different set of regulatory factors and where they have progressed to a more advanced stage of differentiation than ADC. Both groups of DC are, however, heterogeneous, reflecting the continuous turnover that these cells undergo in the lung.

Animals↗
PubMed1991

What is a low-lying placenta?

Transvaginal ultrasonography was performed in 127 women thought to have placenta previa. In all cases of complete previa, placental location was confirmed at cesarean section. Where the placenta was situated in the lower segment of the uterus but did not cover the cervical os the distance from the placental edge to the internal cervical os was measured. This distance was analyzed in relation to the route of delivery. No patient with a placental edge greater than 2 cm from the internal cervical os required cesarean section for the indication of placenta previa, whereas seven of eight patients with a distance of less than or equal to 2 cm underwent cesarean section because of bleeding characteristic of a placenta previa. These preliminary results suggest that transvaginal ultrasonography measurement may indicate the optimal delivery route and make the traditional classification of placenta previa obsolete.

Cesarean Section↗
PubMed1985

Alternative processing and developmental control of the transcripts of the Drosophila abl oncogene homologue.

Drosophila sequences homologous to the abl oncogene are located near the 5' end of a gene (Dash). The Dash gene is transcribed to give long RNAs (5-6 kb) and short RNAs (3.0 kb) that lack some of the internal exons of the gene including some of the sequences coding for the protein kinase domain. The gene is composed of at least five short exons and a long 3' exon. The 3' exon is processed in several alternative ways. It contains an intronic sequence which is spliced out in approximately 50% of the transcripts. S1 mapping shows the existence of five different 3' ends, presumed polyadenylation sites, differing by up to 1 kb. Three of these are maternal-specific while the other two are utilised during development. Dash RNA is most abundant in eggs and early embryos, becomes very rare during larval development and returns in a burst of activity in early pupae.

Animals↗
PubMed1985

Androgen metabolism and apocrine differentiation in human breast cancer.

Metabolism of (7 alpha-3H)testosterone has been measured in 111 human breast cancers and compared retrospectively with the degree of apocrine differentiation in the tumors. Cancers in which apocrine characteristics were a marked feature metabolized significantly more testosterone precursor than those in which apocrine features did not predominate. Higher metabolism was accounted for by increased conversion to 5 alpha-reduced products such as 5 alpha-dihydrotestosterone and 5 alpha-androstanediols.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1985

Androgen receptor activity in human breast cancer and its relationship with oestrogen and progestogen receptor activity.

Androgen receptor activity was measured in tumours from 122 patients with breast cancer. Forty-two tumours (34%) possessed androgen receptors at levels varying from 17 to 210 fmol/mg cytosol protein (mean value 68). No relationship was detected between androgen receptors and menopausal status of the patients and whether or not lymph nodes were invaded with tumour at the time of biopsy. There were, however, significant positive correlations between the presence of androgen receptors and that of oestrogen (P less than 0.05) and of progestogen receptors (P less than 0.025). These relationships suggest that androgen receptors may be of value in predicting the hormone responsiveness of breast tumours but definitive proof of this requires clinical follow-up of the patients studied.

Breast Neoplasms↗
PubMed1985

Cyclic AMP binding proteins in human breast cancer.

The characteristics of a method for measuring cyclic AMP binding proteins in cytosols of human breast cancer are described. Using the assay, binding proteins were demonstrable in all of 100 tumour cytosols. Levels of binding in individual tumours varied from 0.8 to 15 pmol mg-1 cytosol protein (mean value 5 pmol mg-1 cytosol protein) and the dissociation constant ranged from 0.5 to 5.2 X 10(-8)M (mean 1.73 X 10(-8)M). Whilst replicate measurements within a single portion of tumour were reproducible (intra-assay coefficient of variation was between 4.5 and 7.8% and that for inter-assay variation was between 2.1 and 4.0%) there were often considerable differences in levels of binding proteins between different portions of the same tumour. Similar intra-tumour variations have been reported for other binding proteins and steroid receptors. The inter-relationships with such parameters may elucidate whether the differences are associated with variations in cellularity, cell type, or other specific factors.

Breast Neoplasms↗
PubMed1983

Binding of [3H]-methyltrienolone (R1881) by human breast cancers.

The synthetic radioligand [3H]-R1881 binds to both androgen and progestogen receptors; these two types of receptor activity can be separated by competition experiments with radioinert steroids of defined biological activity. Using two standard tissues, rat prostate and human uterus, which are sources of androgen and progestogen receptors respectively, the optimal conditions for the determination of each type of activity were established. For the purposes of routine assay, androgen receptors were quantified after saturation of progestogen receptor sites with 125 nM radioinert R5020 using [3H]-R1881 and increasing concentrations of radioinert R1881. Progestogen receptor activity could be identified using the same radioligand and competition with radioinert progesterone or R5020, though for routine purposes, progestogen receptors were quantified using the more specific radioligand, [3H]-R5020. The binding of [3H]-R1881 to tumour cytosol was examined in 122 human breast cancers. Seventy-two tumours (59%) showed binding. Androgen receptor activity alone was present in 16 tumours, progestogen receptor activity alone in 30 tumours and both types in 26 tumours. Tumours containing progestogen receptor activity also showed binding to the progestogen [3H]-R5020, whilst those containing androgen receptors alone did not. Androgen receptor concentration varied from 17 to 210 fmol binding sites/mg cytosol protein (mean value 68) and the mean Kd was 2.15 X 10(-9) M. Progestogen receptor concentration varied from 25 to 1350 fmol binding sites/mg cytosol protein (mean value 410) and the mean Kd was 1.35 X 10(-9) M. The biological significance of the presence of these types of receptor in human breast cancers is currently being assessed from clinical follow-up.

Animals↗
PubMed1980

Histone genes from Xenopus laevis: molecular cloning and initial characterization.

Histone DNA sequences, were detected in Eco RI fragments of total Xenopus laevis DNA, by hybridization with 32P-labeled h22-DNA, a histone gene repeat unit of the sea urchin Psammechinus miliaris. The about 6 kb-size class, which was found to hybridize, was subsequently integrated into the E. coli plasmid pCR1. A clone was isolated that contains a 5.8 kb EcoRI fragment hybridizing with h22-DNA. A physical map was constructed using the restriction endonucleases BamHI, PstI, HincII, BglII, XbaI, PvuII, XhoI, AvaI, SmaI, HinfI and HpaII. The fragment was not cleaved by KpnI, AvaI, SalI and HindIII. Using this restriction map we were able to determine the gene order by hybridization with purified gene probes derived from h22-DNA. The gene order was found to be H3, H4, H2A and H2B. The localization of the H1 gene was not possible, probably due to its greater evolutionary divergence. Part of the sequence of the H3-gene is presented providing unambiguous evidence on the identity, map position and polarity of this gene.

Animals↗
PubMed1979

Detection of labelled RNA species by contact hybridization.

An improved contact hybridization technique for the analysis of labelled RNA species is presented. The method combines high sensitivity of detection with the high resolution of polyacrylamide gel electrophoresis and should be especially useful for the characterization of transient RNA precursor molecules. Its application to gene mapping is illustrated.

Animals↗
PubMed1978

Genes and spacers of cloned sea urchin histone DNA analyzed by sequencing.

A cloned histone gene cluster of the highly reiterated type from the sea urchin Psammechinus miliaris was analyzed by DNA sequencing. More than half of the 6 kb repeat was sequenced, including coding regions of all five histones, some prelude and trailing sequences lying adjacent to the structural gense, and segments of the AT-rich spacer DNA. The gene cluster does not code for gonad-specific histone variants but may instead be active in early sea urchin development, as indicated by comparison to reference histones. The encoded histones seem not to be derived from longer precursor proteins, not is there any evidence for insert sequences within the coding regions. Sequence similarities exist among the putative ribosome-binding sites adjacent to the initiator codons of individual genes. The AT-rich spacer segments between the genes differ from each other, are made up from relatively simple nucleotide arrangements, but are not repetitious, and apparently do not code for additional large proteins.

Animals↗
PubMed1977

Novel screening procedure for recombinant plasmids.

Lysed bacterial colonies containing potential recombinant plasmids were mixed with molten agar and sealed into slots of an agarose gel. After electrophoresis overnight, the gel was stained with ethidium bromide, which clearly reveals recombinant plasmids. Xenopus laevis ribosomal DNA and histone DNA of Psammechinus miliaris were ligated into pCRI plasmids and screened by this method.

Animals↗
PubMed1976

The arrangement of 18-S and 28-S ribosomal ribonucleic acids within the 40-S precursor molecule of Xenopus laevis.

The arrangement of 18-S rRNA and 28-S rRNA within their 40-S common precursor molecule (pre-rRNA) of Xenopus laevis was investigated by electron microscopic analysis of secondary structure of nascent pre-rRNA chains of oocytes, and by 5'-end analysis of 18-S rRNA and 28-S rRNA hybridized to the EcoRI fragment of rDNA cloned as plasmid pCD42. Secondary structure mapping of phenol-extracted RNA from nucleolar cores revealed complete pre-rRNA chains or molecules at various stages of processing and pre-rRNA molecules apparently lacking one end. In this latter group, which was regarded as representing nascent chains, more than 90% of the molecules had no 28-S rRNA REGION. This shows that the 28-S rRNA sequence is transcribed after the 18-S rRNA region and hence must be located nearer to the 3' end of the pre-rRNA molecule. For 5' end-group determination [3H]uridine-labelled 18-S rRNA and 28-S rRNA were hybridized, as fragments of about 200 nucleotides, to the plasmid pCD42 containing coding sequences for four-fifths of the 18-S rRNA sequence, the external transcribed spacer, the non-transcribed spacer and a tenth of the 28-S rRNA sequence. The RNA was recovered from the hybrids and analyzed for uridine 3',5'-bisphosphate (pUp) after alkaline hydrolysis. The pUp content of the hybridized 18-S rRNA fragments was 20-fold higher than in those of 28-S rRNA, THUS DEMONSTRATING THAT THE 5' END OF THE 18-S rRNA is located next to the external spacer region. From these results it is concluded that the 18-S rRNA is located close to the 5' end of the 40-S pre-rRNA molecule.

Animals↗
PubMed1976

Molecular analysis of the histone gene cluster of psammechinus miliaris: II. The arrangement of the five histone-coding and spacer sequences.

Histone DNA of Psammechinus miliaris was obtained in an enriched form by buoyant density gradient centrifugation and was cleaved into 6 kb repeat units (Birnstiel et al., 1975a) by the action of the specific endonucleases EcoRI and HindIII. Since it was suspected that the 6 kb unit harbored all five histone-coding sequences, the histone DNA unit was subdivided into five segments with the aim of providing five fragments carrying just one coding sequence each. This was achieved by the combined use of EcoRI Hindll, Hindlll, and Hpa I. A physical map was constructed from the overlaps arising in these restriction experiments. Each of the five segments was shown to hybridize uniquely with just one of the five highly purified histone mRNAs (Gross et al., 1976a). By this procedure, the order of the mRNA sequences on the histone DNA was found to be a, c, d, b, e (Gross et al., 1976a), and hence of the protein coding sequences H4, H2B, H3, H2A, and H1. Further evidence is presented that the 6 kb repeat unit, amplified by means of a Murray lambda vector phage, contains AT-rich DNA sequences which would be expected not to code for histone proteins.

Adenine↗
PubMed1976

Molecular analysis of the histone gene cluster of Psammechinus miliaris: III. Polarity and asymmetry of the histone-coding sequences.

Fragments of histone DNA produced by restriction endonucleases contain 5' and 3' termini with defined topologies relative to the histone-coding sequences. After limited resection with lambda-exonuclease, the 6 kb Hindlll histone DNA fragment (see Schaffner et al., 1976) hybridizes to H4 histone mRNA whether or not the DNA has been denatured. This shown that the coding sequence for the histone H4 is proximal to the 3' terminus of the Hindlll restriction fragment. By contrast, lambda-exonuclease digestion of the 6 kb EcoRI histone DNA fragment drastically reduces hybridization of the H4 mRNA. Hence in this molecule, the H4 DNA sequence is near a 5' terminus of the EcoRI restriction fragment. From these results and those described in the preceding paper (Schaffner et al., 1976), the polarity of the H4 gene is therefore 5' H2B leads to H4 leads to H1 3'. Cloned Psammechinus histone DNA (S. G. Clarkson, H. Smith, W. Schaffner, K. Gross, and M. Birnstiel, manuscript submitted for publication) may be strand-separated by electrophoresis. Highly purified histone mRNAs (Gross et al., 1976) all hybridize almost exclusively to the strand of lesser electrophoretic mobility. It follows that all coding sequences are arranged in tandem within the same DNA strand, and that hence they share the same polarity as the H4 DNA sequences. Transcription therefore proceeds in the gene cluster in the direction H4 leads to H2B leads to H3 leads to H2A leads to H1.

Animals↗