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Biomedical subjects

C M Jones

Publications and source records attributed to C M Jones.

At least 19 recordsLinked to original sources
PubMed1992

Speed of intersubunit communication in proteins.

To determine the speed of communication between protein subunits, time-resolved absorption spectra were measured following partial photodissociation of the carbon monoxide complex of hemoglobin. The experiments were carried out using linearly polarized, 10-ns laser pulses, with the polarization of the excitation pulse both parallel and perpendicular to the polarization of the probe pulse. The substantial contribution to the observed spectra from photoselection effects was eliminated by isotropically averaging the polarized spectra, allowing a detailed comparison of the kinetics as a function of the degree of photolysis. These results show that prior to 1 microsecond both geminate ligand rebinding and conformational relaxation are independent of the number of ligands dissociated from the hemoglobin tetramer, as expected for a two-state allosteric model. After this time the kinetics depend on the ligation state of the tetramer. The conformational relaxation at 10 microseconds can be interpreted in terms of the two-state allosteric model as arising from the R to T quaternary conformational change of both unliganded and singly liganded molecules. These results suggest that communication between subunits requires about 1 microsecond and that the mechanism of the communication which occurs after this time is via the R to T conformational change. The optical anisotropy provides a novel means of accurately determining the extinction coefficients of the transient photoproduct. The decay in the optical anisotropy, moreover, provides an accurate determination of the rotational correlation time of 36 +/- 3 ns.

Carboxyhemoglobin↗
PubMed1992

The role of solvent viscosity in the dynamics of protein conformational changes.

Nanosecond lasers were used to measure the rate of conformational changes in myoglobin after ligand dissociation at ambient temperatures. At low solvent viscosities the rate is independent of viscosity, but at high viscosities it depends on approximately the inverse first power of the viscosity. Kramers theory for unimolecular rate processes can be used to explain this result if the friction term is modified to include protein as well as solvent friction. The theory and experiment suggest that the dominant factor in markedly reducing the rate of conformational changes in myoglobin at low temperatures (less than 200 K) is the very high viscosity (greater than 10(7) centipoise) of the glycerol-water solvent. That is, at low temperatures conformational substates may not be "frozen" so much as "stuck."

Carbon Monoxide↗
PubMed1992

The TGF-beta-related DVR gene family in mammalian development.

The genes that encode the bone morphogenetic proteins and the Vg-related proteins are mammalian members of a group of TGF-beta-related genes, designated the DVR family, that includes the decapentaplegic gene of Drosophila and the Vg1 gene of Xenopus. Members of the DVR (decapentaplegic-Vg-related) family have been implicated in diverse processes during development, particularly in epithelial-mesenchymal interactions. The results of our in situ hybridization studies with postimplantation mouse embryos provide evidence for the involvement of DVR family members, particularly DVR-2, DVR-4 and DVR-6, in specific inductive interactions during the development of many organs, including the limb, the whisker follicle and the heart.

Animals↗
PubMed1992

Histoplasmosis in hairy cell leukemia: case report and review of the literature.

Progressive disseminated histoplasmosis (PDH) has been described in only six patients with hairy cell leukemia (HCL). Herein we describe an additional patient with HCL and disseminated histoplasmosis. Additionally, we note that three of seven cases of disseminated histoplasmosis and HCL have occurred in East Texas. PDH is to be suspected in febrile HCL patients in an endemic area who fail to respond to antibacterial therapy. We emphasize that serologic studies are useful in the diagnosis of PDH in HCL patients, and these patients respond well to therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Photodynamic therapy in the treatment of Bowen's disease.

BACKGROUND: The treatment of Bowen's disease in anatomically difficult areas or especially large lesions can challenge accepted modalities of treatment. OBJECTIVE: The purpose of this study was to illustrate the effectiveness of photodynamic therapy in the treatment of Bowen's disease. In addition, photodynamic therapy may be used as adjuvant therapy for difficult lesions. METHODS: Six patients with Bowen's disease in various anatomic sites were treated with photodynamic therapy. Four were in a difficult anatomic site, or were especially large, or both. Photofrin, 1.0 mg/kg, was administered intravenously and laser treatment was given approximately 48 hours later with the argon dye laser. Light was administered at a wavelength of 630 nm and the light dose ranged from 185 to 250 joules/cm2. Treatment was given by surface radiation only. RESULTS: Eight lesions were treated. All showed a complete response at 3 months (100%) and continue to show a complete response at 6 and 12 months. Morbidity was low; the most significant side effects were moderate pain and edema. Healing time varied depending on the size of the lesion. CONCLUSION: Photodynamic therapy is an effective and useful alternative for Bowen's disease, especially those lesions in anatomically difficult areas or those that are especially large.

Adult↗
PubMed1992

Expression and modification of Hox 2.1 protein in mouse embryos.

A polyclonal antibody, alpha Hox 2.1a, has been generated and used to immunolocalize Hox 2.1 protein in mouse embryos. Protein is present in nuclei of all tissues previously shown to express Hox 2.1 RNA. In addition, protein is seen in somites and proximal regions of the limb buds, tissues in which Hox 2.1 RNA expression was not clearly detected previously by in situ hybridization. At the 7 somite stage, protein is detectable in the neural tube up to the level of somite 1, but later retracts to a more posterior position. Immunoblot, in vitro translation, and immunoprecipitation experiments were carried out to characterize the Hox 2.1 protein. The results show that the Hox 2.1 gene produces at least two related phosphorylated proteins present in different proportions in different tissues.

Animals↗
PubMed1992

Isolation of Vgr-2, a novel member of the transforming growth factor-beta-related gene family.

A cDNA clone, Vgr-2, with homology to certain members of the transforming growth factor-beta superfamily has been isolated from a mouse embryo cDNA library. The encoded protein shows significant similarity to members of the Vg-1/decapentaplegic/bone morphogenetic protein subgroup of the transforming growth factor-beta family. Within this group, Vgr-2 is more similar to Xenopus Vg-1 than to any other member so far isolated. The gene is expressed at highest levels during midgestation mouse development, and transcripts are localized by in situ hybridization to the osteogenic zone of developing bone. Vgr-2 is expressed in F9 teratocarcinoma cells, and its RNA levels are down-regulated within 24 h after differentiation with retinoic acid. The genomic organization of Vgr-2 and its location on mouse chromosome 6 are reported.

Amino Acid Sequence↗
PubMed1992

DVR-4 (bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction.

Establishment of mesodermal tissues in the amphibian body involves a series of inductive interactions probably elicited by a variety of peptide growth factors. Results reported here suggest that mesodermal patterning involves an array of signalling molecules including DVR-4, a TGF-beta-like molecule. We show that ectopic expression of DVR-4 causes embryos to develop with an overall posterior and/or ventral character, and that DVR-4 induces ventral types of mesoderm in animal cap explants. Moreover, DVR-4 overrides the dorsalizing effects of activin. DVR-4 is therefore the first molecule reported both to induce posteroventral mesoderm and to counteract dorsalizing signals such as activin. Possible interactions between these molecules resulting in establishment of the embryonic body plan are discussed.

Activins↗
PubMed1991

Alzheimer disease paired helical filament core structures contain glycolipid.

The core structures of sodium dodecyl sulfate extracted, pronase digested paired helical filaments of Alzheimer disease were solubilized by heating in dimethyl sulfoxide. Electron microscopy revealed that after heating in dimethyl sulfoxide, intact paired helical filaments were no longer present in the dimethyl sulfoxide soluble fractions or in the insoluble lipofuscin-containing fractions. Enzyme-linked immunosorbent assays of the various fractions with the monospecific antibody A128 to paired helical filaments demonstrated 96% of the immunoreactivity to be in the dimethyl sulfoxide soluble fraction, and only 4% in the dimethyl sulfoxide insoluble fractions. Lyophilization of the dimethyl sulfoxide soluble supernatant and resuspension in water failed to reassociate the paired helical filaments, but did result in an insoluble precipitate. Analysis of the dimethyl sulfoxide solubilized paired helical filament fraction by nuclear magnetic resonance revealed it to be composed of glycolipid in a form that was distinct from similar fractions isolated from normal aged control brains. The aggregation of an altered glycolipid to form paired helical filaments in Alzheimer disease could explain their insolubility.

Alzheimer Disease↗
PubMed1991

Dynamics of the quaternary conformational change in trout hemoglobin.

The kinetics of conformational changes in trout hemoglobin I have been characterized over the temperature range 2-65 degrees C from time-resolved absorption spectra measured following photodissociation of the carbon monoxide complex. Changes in the spectra of the deoxyheme photoproduct were used to monitor changes in the protein conformation. Although the deoxyheme spectral changes are only about 8% of the total spectral change due to ligand rebinding, a combination of high-precision measurements and singular value decomposition of the data permits a detailed analysis of both their amplitudes and relaxation rates. Systematic variation of the degree of photolysis was used to alter the distribution of liganded tetramers, permitting the assignment of the spectral relaxation at 20 microseconds to the R----T quaternary conformational change of the zero-liganded and singly liganded molecules and spectral relaxations at about 50 ns and 2 microseconds to tertiary conformational changes within the R structure. Analysis of the effect of photoselection by the linearly polarized excitation pulse indicates that a major contribution to the apparent geminate rebinding in the 50-ns relaxation arises from rotational diffusion of molecules containing unphotolyzed heme-CO complexes. The activation enthalpy and activation entropy for the R0----T0 transition are +7.4 kcal/mol and -12 cal mol-1 K-1. Using the equilibrium data, delta H = +29.4 kcal/mol and delta S = +84.4 cal mol-1 K-1 [Barisas, B. G., & Gill, S. J. (1979) Biophys. Chem. 9, 235-244], the activation parameters for the T0----R0 transition are calculated to be delta H = +37 kcal/mol and delta S = +73 cal mol-1 K-1. The similarity of the equilibrium and activation parameters for the T0----R0 transition indicates that the transition state is much more R-like than T-like. This result suggests that in the path from T0 to R0 the subunits have already almost completely rearranged into the R configuration when the transition state is reached, while in the path from R0 to T0 the subunits remain in a configuration close to R in the transition state. The finding of an R-like transition state explains why the binding of ligands causes much smaller changes in the R----T rates than in the T----R rates.

Amino Acid Sequence↗
PubMed1991

Monoclonal antibodies specific for the core protein of the beta-subunit of the gastric proton pump (H+/K+ ATPase). An autoantigen targetted in pernicious anaemia.

The gastric H+/K(+)-transporting adenosine triphosphatase (H+/K+ ATPase) (proton pump) consists of a catalytic alpha-subunit and a recently proposed 60-90-kDa glycoprotein beta-subunit. Using dog gastric membranes as the antigen, we have produced two murine monoclonal antibodies, 4F11 (IgG1) and 3A6 (IgA), which are specific for the 60-90-kDa glycoprotein. The monoclonal antibodies (1) specifically stained the cytoplasm of unfixed and formalin-fixed dog gastric parietal cells; (2) specifically reacted by ELISA with gastric tubulovesicular membranes; (3) recognised epitopes located on the luminal face of parietal cell tubulovesicular membranes, the site of the proton pump, by immunogold electron microscopy; (4) immunoblotted a 60-90-kDa molecule from tubulovesicular membranes and a 35-kDa component from peptide N-glycosidase-F-treated membrane extracts; (5) immunoblotted the 60-90-kDa parietal cell autoantigen associated with autoimmune gastritis and pernicious anemia, purified by chromatography on parietal cell autoantibody- or tomato-lectin-Sepharose 4B affinity columns, and the 35-kDa protein core of this autoantigen; this autoantigen has amino acid sequence similarity to the beta-subunit of the related Na+/K(+)-transporting adenosine triphosphatase (Na+/K+ ATPase) [Toh et al. (1990) Proc. Natl Acad. Sci. 87, 6418-6422]; (6) co-precipitated a molecule of 95 kDa with the 60-90-kDa molecule from 125I-labelled detergent extracts of dog tubulovesicular membranes; and (7) co-purified the catalytic alpha-subunit of the H+/K+ ATPase with the 60-90-kDa molecule by immunoaffinity chromatography of tubulovesicular membrane extracts on a monoclonal antibody 3A6-Sepharose 4B column, indicating a physical association between the two molecules. These results provide further evidence that the 60-90-kDa glycoprotein is the beta-subunit of the gastric H+/K+ ATPase. We conclude that the monoclonal antibodies specifically recognise luminal epitopes on the 35-kDa core protein of the 60-90-kDa beta-subunit of the gastric proton pump, a major target molecule in autoimmune gastritis and pernicious anaemia. These monoclonal antibodies will be valuable probes to study the structure and function of this associated beta-subunit, as well as the ontogeny of the gastric proton pump.

Adenosine Triphosphatases↗
PubMed1991

The parietal cell autoantigens recognized in neonatal thymectomy-induced murine gastritis are the alpha and beta subunits of the gastric proton pump [corrected].

Murine autoimmune gastritis, induced by neonatal thymectomy, bears a striking similarity in pathology to the human autoimmune disease, pernicious anemia. Autoantibodies to parietal cells are found in both murine and human diseases. Monoclonal immunoglobulin G autoantibodies, obtained from neonatally thymectomized mice, have previously been shown to recognize two groups of gastric parietal cell antigens. In the present study, it is shown that two of these monoclonal autoantibodies, designated 1H9 and 2B6, are directed against the alpha subunit and beta subunit, respectively, of the gastric hydrogen-potassium-stimulated adenosine triphosphatase (H+,K(+)-ATPase; proton pump). Monoclonal antibody 1H9 showed reactivity by immunoblotting with a 95-kilodalton component of dog gastric tubulovesicular membranes and with a fusion protein containing the hydrophilic domain of the alpha subunit of the H+,K(+)-ATPase. Monoclonal antibody 2B6 reacted by immunoblotting with the 60-90-kilodalton glycoprotein (beta subunit) of the tomato lectin-purified dog H+,K(+)-ATPase and with the 60-90-kilodalton autoantigen purified with human parietal cell autoantibodies. Monoclonal antibody 2B6 also reacted with the deglycosylated 35-kilodalton core protein of the tomato lectin-purified 60-90-kilodalton beta subunit and of the purified 60-90-kilodalton autoantigen. Parietal cell autoantibody-positive sera from 20 mice with experimentally induced gastritis showed reactivity predominantly with the alpha and/or beta subunit of the gastric H+,K(+)-ATPase. Therefore, it is concluded that the major molecules targeted by parietal cell autoantibodies from mice with neonatal thymectomy-induced murine autoimmune gastritis and from humans with pernicious anemia are identical.

Adenosine Triphosphatases↗
PubMed1991

Involvement of Bone Morphogenetic Protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse.

Bone Morphogenetic Protein-4 (BMP-4) and Vgr-1 are members of the TGF-beta gene family most closely related to the Drosophila Decapentaplegic and Xenopus Vg-1 genes. Members of this gene family have been implicated in diverse processes during embryogenesis including epithelial-mesenchymal interactions. Here, we use in situ hybridization to localize BMP-4 and Vgr-1 transcripts during murine development. BMP-4 mRNA is found in a variety of tissues. In the 8.5 days p.c. embryo, transcripts are localized to the mesoderm posterior to the last somite. Later gestation embryos show expression in developing limbs, the embryonic heart, the facial processes and condensed mesenchymal cells associated with early whisker follicle formation. In the developing central nervous system (CNS), BMP-4 expression is restricted to the floor of the diencephalon associated with pituitary development. In contrast, Vgr-1 transcripts are found along the anteroposterior axis of the CNS, in cells immediately adjacent to the floor plate and in the roof plate extending to the forebrain. Together, the data support the hypothesis that polypeptide growth factors of the TGF-beta superfamily play key roles in the initial stages of neurogenesis and organogenesis during murine development.

Animals↗
PubMed1991

Purification and amino acid analysis of a human macrophage cytotoxicity-inducing factor (MCF).

Recently we have described a CD4+ human T-cell hybridoma Ft.F3 (ATCC HB 9713). This hybridoma produces two proteins having molecular weights of 29 kd (P29) and 14.7 kd (P14.7) that function as activators of human monocyte tumor cytotoxicity and interleukin 1 (IL-1) synthesis (macrophage cytotoxicity-inducing factors, MCFs). Both MCF species were purified to apparent homogeneity, as assessed by two-dimensional (2D) gel electrophoresis, by a combination of dye ligand, ion exchange, and hydrophobic interaction chromatography, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Exhaustive treatment of P29 by endoglycosidase F, performic acid, and 40x molar excess 2-mercaptoethanol failed to generate P14.7 from P29. Antisera raised to P29 recognized only P29 in immunoblots of 2D gels of crude hybridoma supernatant. Amino acid composition analyses of both species are similar but not identical. These MCFs appear to be distinct but possibly related proteins important in the inflammatory response, whereas N-terminal analysis of P29 reveals it to be a previously undescribed cytokine.

Amino Acid Sequence↗
PubMed1990

The 60- to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a beta subunit of the gastric H+/K(+)-ATPase (proton pump).

Autoantibodies in the sera of patients with pernicious anemia recognize, in addition to the alpha subunit of the gastric H+/(+)-ATPase, an abundant gastric microsomal glycoprotein of apparent Mr 60,000-90,000. Herein we have colocalized the glycoprotein and the alpha subunit of the gastric H+/K(+)-ATPase to the tubulovesicular membranes of the parietal cell by immunogold electron microscopy. Moreover, the glycoprotein and the alpha subunit were coimmunoprecipitated, and copurified by immunoaffinity chromatography, with an anti-glycoprotein monoclonal antibody. The pig glycoprotein was purified by chromatography on tomato lectin-Sepharose, and five tryptic peptides from the purified glycoprotein were partially sequenced. The complete amino acid sequence, deduced from the nucleotide sequence of overlapping cDNA clones, showed 33% similarity to the sequence of the beta subunit of the pig kidney Na+/K(+)-ATPase. We therefore propose that the 60- to 90-kDa glycoprotein autoantigen is the beta subunit of the gastric H+/K(+)-ATPase and that the alpha and beta subunits of the proton pump are major targets for autoimmunization in autoimmune gastritis.

Adenosine Triphosphatases↗
PubMed1990

Underwater orthodontics.

A report is presented of a scuba diver who was unable to dive using a normal commercial mouthpiece due to wearing a fixed orthodontic appliance. The situation was resolved with the provision of a customized mouthpiece of simple design and manufacture.

Adolescent↗