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Biomedical subjects

T A Moore

Publications and source records attributed to T A Moore.

At least 73 records · Page 4Linked to original sources

Pan natural killer cell monoclonal antibodies and their relationship to the NK1.1 antigen.

The study of natural killer (NK) has been difficult because they account for a small percentage of peripheral blood and splenic lymphocytes and the paucity of NK specific antigens that have been identified. We have isolated pure populations of C57BL/6 (H-2b) NK cells using the IgG2b monoclonal antibody PK136 (anti-NK1.1). These NK1.1+ cells were used to immunize 129/J (H-2b) mice, and in this report, we describe three new NK specific monoclonal antibodies (SW3A4(IgM), SW4B12(IgG1), and SW2B4(IgG2b] and their relationship to the known murine NK antigen NK1.1. We have further characterized the NK1.1 antigen as a 39 kd molecule which is coded for by a gene which appears to map to chromosome 6.

Animals↗

Phosphorylation results in activation of a cAMP phosphodiesterase in human platelets.

Agents such as prostaglandins E1 and I2 which elevate cAMP levels in platelets also increase cAMP phosphodiesterase activity. Since much of the cAMP phosphodiesterase activity in human platelets is due to the cGMP-inhibited isozyme (Macphee, C. H., Harrison, S. A., and Beavo, J. A. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 6600-6663), we examined the regulation of this isozyme by prostaglandins E1 and I2 in intact platelets. Because this isozyme is a minor component of platelet protein, normally requiring several thousand-fold purification to achieve homogeneity, a specific monoclonal antibody (CGI-5) was utilized to identify and isolate the cGMP-inhibited phosphodiesterase activity. Treatment of intact platelets with the prostaglandins promoted an increase in the phosphorylation state of the cGMP-inhibited phosphodiesterase and a corresponding increase in phosphodiesterase activity. The effect on activity and phosphorylation of the cGMP-inhibited phosphodiesterase was observed within 2 min after intact platelets were exposed to the prostaglandins. The half-maximal effective dose for prostaglandin I2 (10 nM) was approximately 10-fold lower than that for prostaglandin E1. The phosphorylated, cGMP-inhibited isozyme migrated as a 110-kDa peptide following sodium dodecyl sulfate gel electrophoresis. Direct in vitro phosphorylation of the platelet cGMP-inhibited phosphodiesterase by the catalytic subunit of cAMP-dependent protein kinase caused a similar increase in phosphodiesterase activity. Treatment with PKI peptide, a specific inhibitor of cAMP-dependent protein kinase, blocked the phosphorylation and the effect on activity. Taken together, the data strongly suggest that the effects of prostaglandins E1 and I2 on platelet phosphodiesterase activity are mediated by a direct cAMP-dependent protein kinase-catalyzed phosphorylation of the cGMP-inhibited phosphodiesterase isozyme.

3',5'-Cyclic-AMP Phosphodiesterases↗

Nonunion of the tibial shaft.

Charts of 70 patients with 72 nonunions of the tibial shaft were reviewed, identifying 39 aseptic and 33 infected nonunions. Most nonunions started as an open fracture (76%), although 4 of the 12 patients with closed fractures became infected following surgical treatment. Seven patients (all of the septic group) had a below-knee amputation as their only procedure; amputation was eventually necessary for three other patients. In total, 90% of the aseptic nonunions healed, as did 79% of infected nonunions not amputated at the first procedure. The average time from injury to union was approximately 36 months for both aseptic and infected nonunions. Numerous complications occurred during treatment of tibial nonunions, the most common (61%) being angulation of greater than 5 degrees in at least one plane.

Adolescent↗

Investigations into the effect of acid on the spectral and kinetic properties of purple membrane from Halobacterium halobium.

The formation and reversal of the acid species of purple membrane generated below pH 4.00 (22 degrees C) is studied together with the photochemical cycle over the pH range 6.40--3.20. The buffering capacity of the membrane reaches a peak at pH 4.30, indicating the possibility of a conformational change taking place. The generation of the new spectral species can take place in the dark and is unaffected by the addition of reducing agents. Kinetic parameters measured indicate that the group being titrated below pH 4.00 could be the same as that protonated in the formation of intermediate O. The temporal placement of intermediate O after M in the photochemical cycle is shown to be incompatible with the data presented here. Reneutralization of acidified purple membrane shows that the spectral changes in acid are reversible but the phototransient properties are altered.

Bacteriorhodopsins↗

Effects of modification of the tyrosine residues of bacteriorhodopsin with tetranitromethane.

Treatment of the purple membrane of Halobacterium halobium with tetranitromethane led to modification of tyrosine residues. Modification of more than 3-4 tyrosine residues per bacteriorhodopsin monomer caused a decrease in the light-induced proton-pumping ability of purple membrane in synthetic lipid vesicles, loss of the sharp X-ray-diffraction patterns characteristic of the crystal lattice, loss of the absorbance maximum at 560 nm, and change in the buoyant density of the membrane. No modification of lipid was detected. These changes were interpreted as a gradual denaturation of the protein component such that when 8-9 tyrosine residues are modified, no proton pumping is observed. Modification of less than 3-4 tyrosine residues with tetranitromethane caused an increse in light-induced proton pumping. It was possible to generate partly modified purple membrane which had completely lost the property of diffracting X-rays into the sharp pattern observed with native purple membrane, but which still retained the ability to pump protons in a vectorial manner. Retention of crystal lattice is not essential for proton pumping.

Bacteriorhodopsins↗

Studies of an acid-induced species of purple membrane from Halobacterium halobium.

A new spectral species of the purple membrane of Halobacterium halobium has been observed below pH 3.2. The formation of this new species is temperature-dependent and is favoured by increasing temperature up to the physiological range of the organism. The rate of formation at pH 3.0 and 22 degrees C is 7.9 x 10-3s-1. The spectral distribution and temperature-dependence of the new species suggest that it may be phototransiet O, stabilized by low pH. Flash-photolytic experiments in the pH range 7.2-2.7 show a pH-dependence corresponding to the static events and are consistent with a single protonation of bacteriorhodopsin below pH 3.22. These results can also be interpreted in terms of the stabilization of phototransient O at low pH. The temperature-dependence of the formation of the acid-induced species may reflect a relationship with the phase transition of the membrane.

Bacteriorhodopsins↗

Delayed splenic rupture: diagnosed by culdocentesis.

Culdocentesis is a valuable asset in the diagnosis of hemoperitoneum in women. A case report of delayed splenic rupture diagnosed by this means emphasizes its usefulness. When compared to paracentesis and peritoneal lavage, culdocentesis is more rapid, theoretically more sensitive, and easier to perform. It is a valuable diagnostic tool.

Adult↗

Hepatoma occurring two decades after hepatic irradiation.

Hepatoma has been related to chemical, dietary, metabolic, infectious, and genetic factors. therapeutic hepatic irradiation has never been associated with hepatoma. A case of hepatocellular carcinoma is presented that occurred two decades after radiotherapy for presumed hepatic hemangioma. Radiation-related liver disease is discussed in general, with emphasis placed on radiation hepatocarcinogenesis.

Carbon Tetrachloride Poisoning↗

Ligand binding to ferrocytochrome c at high pH.

Ferrocytochrome c has been shown to bind two molecules of CO at pH 14. The second CO is thought to be bound only when the cytochrome c molecule is denatured, and once bound appears to be spectrally silent. Insolubilization of native cytochrome c prevents the binding of the second CO molecule. A scheme is proposed to explain these observations based on evidence from static titrations and flash-photolysis experiments, use of carboxymethyl cytochrome c and insoluble cytochrome c, and use of cyanide instead of CO as a ligand.

Carbon Monoxide↗

A method for investigating the effect of temperature on the 695 nm band of insoluble cytochrome c.

A method is described for computer analysis of simple spectrophotometric changes in particulate systems, and this has been applied to the bleaching of the 695 nm band of insoluble ferricytochrome c by temperature. The results show that insolubilization has no effect on the standard enthalpy change but lowers the value for the standard entropy change. This effect appears to be independent of the concentration of the gel matrix to which the cytochrome c is bound, but dependent on the ionic strength of the surrounding solution.

Animals↗