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Biomedical subjects

L Morgan

Publications and source records attributed to L Morgan.

At least 91 records · Page 5Linked to original sources
PubMed1995

Mitogen activation of a nuclear alkaline phosphatase in normal activated lymphocytes.

B cell differentiation is punctuated by V(D)J joining in the heavy chain of the pro-B cell, VJ joining in the light chain of the pre-B cell, switch recombination, and somatic hypermutation in the mature B cell. The regulatory signals controlling these events and the developmental program leading to them is poorly understood. We have identified a new phosphatase activity that is expressed in lymphocytes and for which high expression is restricted to mature B cells. This new phosphatase is transiently expressed in nuclear extracts of mitogen-activated splenic B cells. The phosphatase is a monoesterase that is active on both dNMPs and pNPP. The phosphatase has been partially purified by column chromatography and is inhibited by orthovanadate, molybdate, tetramisole, and EDTA and requires Mn2+ for activation. Monoesterase activity requires a pH above the neutral range. The activity profile in the presence of the inhibitors and the requirement for basic pH suggest that this enzyme is an alkaline phosphatase.

Alkaline Phosphatase↗
PubMed1995

Longitudinal change of refractive error in infants during the first year of life.

Using cycloplegia, the change in ametropia of 113 infants was followed at 3 month intervals over the first year of life. Scatterplots of the spherical equivalent power show that the dioptric differences exhibit a significant myopic shift of -0.38 ds between 26 and 36 weeks and -0.38 ds between 36 and 52 weeks. The spread of the dioptric differences (95% CI) does not appear to be related to the magnitude of the ametropia present and decreases with time. By 12 months of age the frequency distribution of the spherical equivalent appears to become leptokurtic as it is in the adult. On average the astigmatism was of low degree (less than 1 dioptre cylinder) and with the rule. Anisometropia was rarely seen. The results of this longitudinal study point to an optimal time for screening and perhaps prescribing for 'abnormal' refractive error between 9 and 12 months of age.

Aging↗
PubMed1995

Autonomous nodular hyperplasia of the adrenal cortex: tertiary hypercortisolism?

Two cases of Cushing's syndrome are reported in which apparently autonomous adrenal adenomata were associated with the presence of pituitary tumours. In one case the patient was apparently cured by unilateral adrenalectomy, although she was noted to have radiological evidence of an intrasellar tumour; serum cortisol was not suppressed by dexamethasone and ACTH was undetectable. Serum ACTH in the second case was initially 31 ng/l but became undetectable during the course of investigation. Transsphenoidal removal of a corticotroph adenoma did not affect serum cortisol and she proceeded to unilateral adrenalectomy. The pathogenesis of autonomous macronodular hyperplasia is discussed, as well as the options for management.

Adenoma↗
PubMed1995

Melatonin and adjustment to phase shift.

The pineal hormone melatonin has clear circadian phase-shifting effects in humans which have recently been formalized as a phase response curve. Its potential use in circadian rhythm disorders has been investigated in field studies of jet lag and shift work and in simulated phase shift. A substantial amount of information indicates that in the majority of subjects it hastens adaptation of both subjective and objective measures to forced shifts in time cues with few reported side-effects. Field studies of its use in adaptation to shift work are sparse and preliminary but the first indications are positive. In some blind subjects with sleep disturbance it can stabilize sleep onset time without necessarily entraining all circadian rhythms and it can advance sleep timing in delayed sleep-phase insomnia. Acute suppression of core body temperature may be an integral part of the phase-shifting mechanism.

Journal Article↗
PubMed1995

Longstanding proliferation of CD3 negative large granular lymphocytes preceding the development of high grade non-Hodgkin's lymphoma.

A patient with a persistent CD3 negative large granular lymphocyte (LGL) proliferation with immunophenotypic and functional characteristics of natural killer cells is described. The LGL proliferation persisted and six years after diagnosis the patient developed a high grade B cell non-Hodgkin's lymphoma. Molecular studies demonstrated clonal B cell populations in the peripheral blood, distinct from that identified in the lymphoma, both at presentation with non-Hodgkin's lymphoma and at complete remission following combination chemotherapy. It is postulated that T cell dysregulation associated with the CD3 negative LGL proliferation may have led to B cell dysfunction and loss of normal B cell control, with the subsequent development of a clonal B cell lymphoproliferative disorder.

Adult↗
PubMed1994

Functional analysis of conserved cysteine residues in the catalytic subunit of the yeast vacuolar H(+)-ATPase.

The A subunit of the yeast vacuolar ATPase contains three highly conserved cysteines: Cys-261, Cys-284, and Cys-538. Cys-261 is located within the nucleotide-binding P-loop. Each of the conserved cysteines, and one nonconserved cysteine, Cys-254, were altered to serine by site-directed mutagenesis, and the effects on growth at pH 7.5 were determined. The Cys-254-->Ser, Cys-261-->Ser and the double mutants all grew at pH 7.5 and contained nitrate- and bafilomycin-sensitive ATPase activity. However, the ATPase activities of the Cys-261-->Ser and the double mutants were insensitive to the sulfhydryl group inhibitor, N-ethylmaleimide, demonstrating that Cys-261 is the site of inhibition by N-ethylmaleimide. Changing either Cys-284 or Cys-538 to serine prevented growth at pH 7.5. Cys-284 and Cys-538 thus appear to be essential cysteine residues which are required either for assembly or catalysis.

Base Sequence↗
PubMed1994

Analysis of nickel refinery dusts.

After characterization of bulk samples by inductively coupled plasma emission spectroscopic (ICP-ES) quantitative analysis and X-ray powder diffraction studies, single particle techniques using quantitative image analysis, scanning electron microscopy--energy dispersive analysis by X-ray, and finally laser beam ionization mass spectrometry analysis (LIMA) for surface analysis have been applied to historical nickel refinery dust samples from the nickel refining plant at Clydach in Wales. There were two historical samples of processed material from 1920 and 1929. These samples had a remarkably small particle size range, mean 3 microns and range, 0.75-24 microns. The most significant difference in elemental composition was the presence of 10% arsenic in the 1920 sample compared with 1% in the 1929 sample. The X-ray spectra revealed the presence of NiO in both. However, surprisingly, CuO was identified only in the 1929 sample. Of particular interest was the presence of a component, in the 1920 sample only, identified as the mineral orcelite, a copper-iron-nickel-arsenide-sulphide mineral, predominantly, Ni5-XAs2. Using the LIMA technique, it was found that in both samples, arsenic and arsenic derivative peaks are prominent, indicating the surface availability of arsenic compounds.

Arsenic↗
PubMed1994

Characterization of ligands of a high-affinity metal-binding site in the latent chloroplast F1-ATPase by EPR spectroscopy of bound VO2+.

Vanadyl, (V = O)2+, is able to substitute for Mg2+ as a cofactor for ATPase activity catalyzed by the chloroplast F1-ATPase (CF1). Mg2+-dependent ATPase activity was also observed with CF1 that contained VO(2+)-ATP bound specifically to the noncatalytic N2 site. Modulation of the Mg(2+)-ATPase activity induced by VO2+ bound at this site indicates that the metal bound to the noncatalytic site affects catalytic activity. When CF1 is depleted of nucleotides from all but the N1 site, a single Mg2+ remains bound at a site designated M1. Addition of VO2+ to the depleted protein gives rise to an EPR spectrum characteristic of a CF1-bound VO2+ species. The binding curve of the VO2+ complex to latent, nucleotide-depleted CF1 was determined by the integrated intensities of the -5/2 parallel peak in the EPR spectrum as calibrated using atomic absorption spectroscopy. Under these conditions, VO2+ binds cooperatively to approximately two sites designated M2 and M3. Three-pulse ESEEM spectra of the CF1-VO2+ complex contain two intense modulations with frequencies and field-dependent behavior that show that they are from a directly coordinated 14N nucleus. Analysis of the bound VO2+ by ENDOR spectroscopy revealed the presence of a single group of protons associated with an equatorial amino or water ligand that is exchangeable with solvent. Using the additivity relation for hyperfine coupling, the most probable set of equatorial ligands to the VO2+ bound to CF1 under these conditions consists of one lysine nitrogen, two carboxyl oxygens from aspartate or glutamate, and one water.

Adenosine Triphosphate↗
PubMed1994

Direct measurement of the binding of RAS to neurofibromin using a scintillation proximity assay.

Protein-protein interactions are of major importance in many cellular processes. When no enzymic activity is involved, assays for direct binding are required. One such example is the relatively weak interaction between oncogenic Ras and the GTPase-activating protein neurofibromin (NF1). The complex between the catalytic domain of NF1 and the GTP-form of oncogenic Ras protein dissociates rapidly; hence, equilibrium binding must be quantitated. Scintillation proximity assay (SPA) technology, a radioisotopic technique that requires no separation step, was used to characterize this interaction. Leu-61 Ras complexed with [3H]GTP was generated by nucleotide exchange in the presence of a GTP-regenerating system. A SPA signal was obtained when radiolabeled Ras was mixed with NF1 fused with glutathione S-transferase (GST), anti-GST, and protein A-coated SPA beads. This signal was abolished when any of the components were omitted and also by the addition of NaCl, which potently reduces the affinity of interaction between Ras and NF1. The neutralizing anti-Ras monoclonal antibody Y13-259 and the detergent n-dodecyl maltoside, a specific inhibitor of NF1 catalytic activity, both abolished the SPA signal from the NF1/Ras assay but neither affected a control SPA signal in which a [3H]GTP.GST-Ras fusion protein was bound to protein A-coated SPA beads. This technology could be readily extended to the measurement of other protein-protein interactions and could form the basis for high-throughput screens for the discovery of novel therapeutic agents.

Escherichia coli↗
PubMed1994

The Schwann cell precursor and its fate: a study of cell death and differentiation during gliogenesis in rat embryonic nerves.

We have characterized a cell, the Schwann cell precursor, that represents a distinct intermediate differentiation stage in the process by which Schwann cells are generated from neural crest cells. The Schwann cell precursor shows radical differences from Schwann cells which include death regulation, antigenic phenotype, pattern of cell-cell interaction, migratory behavior, and morphology. In the nerves of the rat hind limb, Schwann cells are irreversibly generated from these during a brief period, essentially embryonic days 15-17. We also provide evidence that the survival of Schwann cell precursors is regulated by neurons and identify basic fibroblast growth factor as a potential key regulator of apoptosis in Schwann cell precursors and of precursor to Schwann cell conversion. These findings have implications for our understanding of gliogenesis in the peripheral nervous system.

Animals↗