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Biomedical subjects

G R Moore

Publications and source records attributed to G R Moore.

At least 109 records · Page 6Linked to original sources
PubMed1989

A case of adult-onset dementia with argyrophilic grains.

A case of progressive dementia in a 68-year-old woman was characterized by the postmortem finding of widespread argyrophilic grains in the cerebral cortex. The grains consisted of 10- to 13-nm filaments in deposits ranging up to 9 microns in length and 3 microns in diameter. The grains stained positive with Alz-50 monoclonal antibody. Cortical brain tissue levels were minimally elevated for acetylcholinesterase, moderately reduced for choline acetyltransferase, and sharply reduced for glutaminase. Although the case was clinically indistinguishable from Alzheimer's disease, plaque and tangle pathological findings were absent. We confirm cortical changes of the type described by Braak and Braak and provide additional data on subcortical changes in this case.

Aged↗
PubMed1989

Cerebellar degeneration in neuroleptic malignant syndrome: neuropathologic findings and review of the literature concerning heat-related nervous system injury.

A selective subtotal cerebellar neuronal degeneration was found in a patient who died 4 1/2 months after suffering neuroleptic malignant syndrome (NMS), a rare, potentially fatal disorder associated with neuroleptic medications. It is suggested that the cerebellar neuronal degeneration in this case was due to hyperpyrexia, a cardinal clinical feature of NMS. Similar pathologic findings appear not to have been previously reported in NMS but have been described in heat-induced central nervous system (CNS) injury. The findings imply that a cerebellar syndrome might be encountered in patients who survive NMS complicated by a particularly high febrile course.

Adult↗
PubMed1989

Schistosomiasis associated with rupture of the appendix in pregnancy.

Acute appendicitis is among the most common indications for exploratory laparotomy during pregnancy. Although usually pyogenic in origin, parasitic infections account for a small percentage of cases. We report here the association of pregnancy and appendicitis caused by Schistosoma japonicum. Schistosomiasis is a very common complication of pregnancy, with 250,000,000 persons infected worldwide, including 20% of pregnant women living in hyperendemic areas. Schistosome egg masses can lodge throughout the body and cause acute inflammation of the appendix, fallopian tube, liver, and spleen. Congestion of pelvic vessels during pregnancy facilitates passage of eggs into the villi and intervillous spaces, causing an inflammatory reaction. Fetal anoxia and subsequent death has been attributed to heavy infestation of the placenta. Tourism, far-ranging military actions, and immigration make this disease a potential challenge for practitioners everywhere.

Adult↗
PubMed1988

N.m.r., e.p.r. and magnetic-c.d. studies of cytochrome f. Identity of the haem axial ligands.

N.m.r.-, magnetic-c.d.- and e.p.r.-spectroscopic studies of oxidized and reduced cytochrome f from charlock, rape and woad are reported. Comparison of the spectra with corresponding spectra of other haem proteins, including horse and yeast cytochromes c, bovine cytochrome b5 and n-butylamine adduct of soya-bean leghaemoglobin support the hypothesis [Siedow, Vickery & Palmer (1980) Arch. Biochem. Biophys. 203, 101-107] that lysine is the sixth ligand of native cytochrome f. Detailed analysis of the e.p.r. spectrum of ferricytochrome f indicates that its principle g-values are 3.51, 1.70 and less than 1.3, and not 3.48, 2.07 and 1.6 as previously suggested [Siedow, Vickery & Palmer (1980) Arch. Biochem. Biophys. 203, 101-107]. The observation of a one-proton intensity resonance at -3.27 p.p.m. in the 1H-n.m.r. spectrum of ferrocytochrome f, coupled with the absence of a methionine methyl resonance from the spectral region to low frequency of -2 p.p.m., is suggested to be a general indicator of lysine co-ordination.

Animals↗
PubMed1988

Proton-NMR studies show that the Thr-102 mutant of yeast iso-1-cytochrome c is a typical member of the eukaryotic cytochrome c family.

The Thr-102 mutant of yeast iso-1-cytochrome c is a useful system for the study of structure-function relationships in this important class of electron transfer proteins, but little is known about its structure. Furthermore, few assignments of individual amino acid residues in yeast iso-1-cytochrome c have been made by proton NMR. Here we report assignments for nearly half of the amino acids in the reduced Thr-102 mutant of yeast iso-1-cytochrome c. We also report assignments for the oxidized Thr-102 mutant. While the crystal structure of the reduced iso-1-cytochrome c (N. B. not the Thr-102 mutant) has been reported, there is currently little structural information concerning its solution structure and none concerning the oxidized protein. There is also no information concerning the structure of either oxidation state of the Thr-102 mutant. Comparison of the chemical shift and NOE data for the reduced Thr-102 mutant and comparison of paramagnetic shifts for analogous residues between this mutant and horse-heart and tuna cytochromes c reveal that both the basic fold of Thr-102 yeast iso-1-cytochrome c and the region around the site of the mutation are the same as those found in the latter two proteins. It is concluded that the results from structure function studies using the Thr-102 mutant will be applicable to eukaryotic cytochrome c in general. This knowledge allows us to proceed to a description of some mutants of yeast iso-1-cytochrome c in the next paper.

Amino Acids↗
PubMed1988

Ion binding to cytochrome c.

This paper is a further study of ion binding to protein surfaces and builds on the studies of the binding of [Cr(CN)6]3- and [Fe(edta)(H2O)]- previously reported [Williams et al. (1982) FEBS Lett. 15, 293-299; Eley et al. (1982) Eur. J. Biochem. 124, 295-303]. In the present paper the binding of polyaminocarboxylate complexes of gadolinium have been studied. Eight ion-binding sites have been identified on the surface of cytochrome c. These exhibit different binding specificities which, in some cases, are not full understood. However it is clear that simple outer-sphere interactions are not the sole determining factor for the association of metal ion complexes with proteins. The NMR paramagnetic difference spectrum method has been shown to be good at locating binding sites and revealing qualitative differences in their relative affinities for a range of complex types. However the use of relaxation probes is not a good method for the quantitative determination of binding constants; for this, isostructural shift probes must be sought.

Amino Acids↗
PubMed1988

1H-n.m.r. and c.d. studies of haem orientational disorder in sperm-whale myoglobin and human haemoglobin.

1H-n.m.r. and c.d. studies on sperm-whale myoglobin show that the c.d. signal in the Soret region is inversely and linearly related to the proportion of minor isomer present. An alternative method, 'pH jump', is described for inducing orientational disorder in sperm-whale myoglobin without recourse to reconstitution. 1H-n.m.r. studies on human haemoglobin A indicate little heterogeneity in freshly isolated haemoglobin A, but the effect is enhanced in freeze-dried Sigma haemoglobin A.

Animals↗
PubMed1988

On the energetics of conformational changes and pH dependent redox behaviour of electron transfer proteins.

Calculations of the electrostatic interaction energies for four metalloproteins that carry out electron transfer are reported. Each protein has a pH dependent redox potential from which the measured electrostatic interaction energy is obtained. The calculations were made using the X-ray structure coordinates and a semimacroscopic model of the interactions. For cytochrome c-551 and HIPIP the calculated and observed interaction energies were found to be approximately the same, in agreement with the fact that significant conformational changes do not accompany the ionisations. For cytochrome c2 and azurin, however, major differences were found between the calculated and observed values. These are accounted for primarily by the occurrence of significant conformational changes accompanying the ionisations. The reorganisation energies for these conformational changes are approximately 7.0 and approximately 11.1 kJ.mol-1, respectively.

Azurin↗
PubMed1988

Induction of oligodendrocyte proliferation and remyelination after chronic demyelination. Relevance to multiple sclerosis.

Optic nerve and spinal cord tissue from untreated guinea pigs with chronic relapsing experimental autoimmune encephalomyelitis, guinea pigs with experimental autoimmune encephalomyelitis in which the disease was treated with injections of myelin basic protein (MBP) combined with galactocerebroside (GC), and normal guinea pigs, has been studied morphologically, immunocytochemically and morphometrically. MBP/GC treatment induced widespread proliferation of oligodendrocytes and extensive central nervous system (CNS) remyelination in tissue from both sites. Whereas some oligodendrocytes within lesions from treated animals appeared to be derived from surviving cells which underwent mitosis, the frequent occurrence of nests of oligodendrocytes at the periphery of nerve fiber fascicles in optic nerve among perivascular astrocytic elements, raises the possibility that remyelinating oligodendrocytes might possess progenitors located in these regions. Observations from multiple sclerosis lesions showed that oligodendrocyte proliferation and CNS remyelination occur in human subcortical white matter, but to a lesser degree than that seen in the CNS of MBP/GC/treated guinea pigs. Immunocytochemical examination of CNS tissue from experimental autoimmune encephalomyelitis animals confirmed the morphologic identification of oligodendroglia. Preliminary morphometric analysis confirmed the impression of an increase in oligodendroglial cells in MBP/GC-treated animals. This increase was somewhat obscured statistically by a concomitant rise in the number of fibrous astrocytes. In view of the ability of oligodendrocytes to proliferate and produce new myelin in multiple sclerosis, the possibility is raised that an experimental immunologic approach similar to that employed here might have a beneficial effect in the human disease.

Animals↗
PubMed1988

Immunogold localization and analysis of IgG during immune-mediated demyelination.

In both experimental allergic encephalomyelitis and multiple sclerosis, receptor-mediated phagocytosis of myelin debris via clathrin-coated pits on the surface of macrophages has been implicated in the disease process. Furthermore, it has been postulated that IgG serves as the ligand responsible for binding myelin fragments to the clathrin-coated pit. The present immunoelectron microscope study on acute experimental allergic encephalomyelitis in guinea pigs has examined actively demyelinating lesions with a postembedding immunogold technique, utilizing a primary antibody to the Fc portion of IgG and a secondary antibody conjugated to colloidal gold. The results have shown staining for IgG over extracellular fibrin, scattered sites on the macrophage surface, empty clathrin-coated pits and occasionally, clathrin-coated pits containing myelin droplets. Within the macrophage, the tips of whorls of myelin debris were focally labeled. These findings support the notion that IgG serves a role in the uptake of myelin during autoimmune demyelination and might serve as the ligand for receptor-mediated phagocytosis of myelin. However, based upon the relative infrequency of coated pits containing myelin, other mechanisms of phagocytosis are probably also operative. These findings might also have relevance to the pathogenesis of the multiple sclerosis plaque.

Animals↗
PubMed1987

NMR study of the interaction between cytochrome b5 and cytochrome c. Observation of a ternary complex formed by the two proteins and [Cr(en)3]3+.

The interaction between horse cytochrome c and the tryptic fragment of bovine liver microsomal cytochrome b5 in the absence and presence of [Cr(ethylenediamine)3]Cl3 was studied by 1H NMR spectroscopy. The protein-protein interaction region on cytochrome b5 was found to be different from the [Cr(en)3]3+-binding region. The solvent-exposed propionate-bearing edge of the haem of cytochrome b5 is accessible to [Cr(en)3]3+ in the interprotein complex.

Animals↗
PubMed1987

Critical threshold for dose of myelin basic protein in murine autoimmune encephalomyelitis.

The clinical and pathologic features of experimental allergic encephalomyelitis (EAE) in the SJL mouse are described after inoculation with different amounts of myelin basic protein (MBP) in adjuvant. A dose threshold was apparent in that 400 micrograms produced the most severe central nervous system (CNS) changes. These comprised an extensive multifocal destructive myelitis with minimal demyelination. Doses greater than 400 microgram produced less white matter pathology and showed demyelinative rather than destructive lesions. No CNS parenchymal changes were seen in animals given less than 400 micrograms. Inflammation was invariably present in all animals showing CNS pathology, a prominent cellular component of which was the polymorphonuclear leukocyte. These findings illustrate the relationship of clinical signs and pathologic changes to the dose of MBP administered. Thus, it has been shown that the dose requirements for MBP-induced EAE in the SJL mouse are different from and greater than those for other species and that, unlike rats and guinea pigs, lesions were more extensive. Although demyelination was present, lesions tended to be destructive in type. This murine MBP model may serve as an experimental analog for the acute destructive myelopathies occasionally associated with the human autoimmune demyelinating disorders.

Animals↗
PubMed1987

Chronic relapsing necrotizing encephalomyelitis produced by myelin basic protein in mice.

Chronic relapsing experimental autoimmune encephalomyelitis is commonly seen in a number of species after a single injection of whole white matter in adjuvant but not after inoculation with myelin basic protein, the major encephalitogen of central myelin. In the present report on large groups of SJL mice, we describe a form of chronic relapsing experimental autoimmune encephalomyelitis with destructive lesions after a single inoculation of myelin basic protein in complete Freund's adjuvant. This condition was studied for up to 19 months postinoculation and was characterized by a relapsing-remitting or a chronic progressive course, usually with a prolonged latent period. Higher doses of 400 and 800 micrograms of myelin basic protein were more effective in inducing this condition than were lower doses of 100 and 200 micrograms. Large lesions were apparent in the white matter. These comprised widespread destruction and Wallerian degeneration with some demyelination towards the margins. Demyelination was an initial, albeit transient, event which was subsequently masked by nerve fiber destruction. Polymorphonuclear leukocytes were early and prominent components of the inflammatory infiltrate and together with macrophages appeared to be involved in the lysis of myelin and axons. Thus, despite the clinical similarities, these features contrast the model with the more purely demyelinative lesions of chronic relapsing experimental autoimmune encephalomyelitis in other species and multiple sclerosis in man.

Adjuvants, Immunologic↗
PubMed1986

The modulation of cytochrome c electron self-exchange by site-specific chemical modification and anion binding.

The site-specific chemical modification of horse heart cytochrome c at Lys-13 and -72 using 4-chloro-3,5-dinitrobenzoic acid (CDNB) increases the electron self-exchange rate of the protein. In the presence of 0.24 M cacodylate (pH* 7.0) the electron self-exchange rate constants, kex, measured by a 1H NMR saturation transfer method at 300 K, are 600, 6 X 10(3) and 6 X 10(4) M-1 X s-1 for native, CDNP-K13 and CDNP-K72 cytochromes c respectively. Repulsive electrostatic interactions, which inhibit cytochrome c electron self-exchange, are differentially affected by modification. Measurements of 1H NMR line broadening observed with partially oxidised samples of native cytochrome c show that ATP and the redox inert multivalent anion Co(CN)3-6 catalyse electron self-exchange. At saturation a limiting value of approximately 1.4 X 10(5) M-1 X s-1 is observed for both anions.

Adenosine Triphosphate↗