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Biomedical subjects

S Russell

Publications and source records attributed to S Russell.

At least 109 records · Page 6Linked to original sources

Mutation of a protein kinase C phosphorylation site in the erbB protein of avian erythroblastosis virus.

Tumor promoter-stimulated phosphorylation of threonine 98 of the erbB protein of avian erythroblastosis virus (AEV) correlates with inhibition of erbB-dependent mitogenesis. To more clearly define the role of phosphorylation of this residue in regulation of the activity of the erbB protein, we have constructed erbB mutations which encode alanine (Ala-98), tyrosine (Tyr-98), or serine (Ser-98) at position 98. The biosynthesis and stability of the three mutant proteins were similar to those of the wild-type erbB protein, and all three retained the ability to transform chicken embryo fibroblasts. Treatment of transformed CEF with 12-tetradecanoylphorbol-13-acetate (TPA) stimulated incorporation of 32Pi into wild-type and mutant erbB proteins and resulted in a slight decrease in the electrophoretic mobilities of all the erbB proteins. Tryptic maps of erbB phosphopeptides showed no endogenous or TPA-stimulated phosphorylation of alanine 98 or tyrosine 98 in cells transformed by the Ala-98 and Tyr-98 mutants. Analysis of tryptic phosphopeptides by high-pressure liquid chromatography revealed that TPA treatment of cells stimulated phosphorylation of other sites of the erbB protein in addition to threonine 98. A high endogenous level of phosphorylation of serine 98 of the Ser-98 mutant protein was found, and TPA treatment of cells did not result in further phosphorylation of this residue. Cells transformed by wild-type and mutant AEV were equally sensitive to TPA-dependent inhibition of growth in soft agar and TPA-dependent inhibition of [3H]thymidine incorporation. TPA treatment inhibited tyrosine phosphorylation to a similar extent in cells transformed by wild-type or Ala-98 AEV. These data indicate that phosphorylation of threonine 98 of the erbB protein is not responsible for TPA-dependent inhibition of growth of AEV-transformed cells or TPA-induced inhibition of erbB-dependent tyrosine phosphorylation. TPA-stimulated phosphorylation of the erbB protein at other sites may mediate these effects. The data also show that subtle changes in a phosphorylation site (i.e., changing threonine to serine) can drastically alter recognition by protein kinases.

Alpharetrovirus↗

Comparison of the efficacy of naproxen sodium and dihydrocodeine tartrate in the treatment of post-operative pain.

A single-blind, parallel study was carried out in 54 patients with post-operative pain after minor orthopaedic procedures to compare the efficacy and tolerance of naproxen sodium and dihydrocodeine tartrate. Patients were allocated at random to receive oral treatment as soon as analgesia became necessary with an initial dose of either 550 mg naproxen sodium or 30 mg dihydrocodeine tartrate, then doses of 275 mg and 30 mg, respectively, when required up to a maximum of 5 doses per day for 3 days. Assessments were made of pain severity and pain relief 2 and 4 hours after the first dose and at the end of each day. The results indicated that naproxen sodium gave statistically significantly greater pain relief than dihydrocodeine tartrate after the first dose. Both treatments were well tolerated and few side-effects were reported. Three patients in each group were withdrawn due to lack of efficacy (combined with adverse effects in 1 naproxen sodium patient), and 1 patient in each group was withdrawn because of side-effects.

Administration, Oral↗

Calcified cytoid bodies in acquired immunodeficiency syndrome.

The postmortem histopathologic findings of eyes from two patients with acquired immunodeficiency syndrome (AIDS) are presented. Both patients had succumbed to multiple opportunistic infections. All of the eyes demonstrated calcified cotton-wool patches of the retina. To date, there have been no prior descriptions of calcification of cotton-wool spots (CWS). The pathophysiologic mechanisms unique to AIDS that allow some of these CWSs to calcify have yet to be determined.

Acquired Immunodeficiency Syndrome↗

Interaction of asialo von Willebrand factor with glycoprotein Ib induces fibrinogen binding to the glycoprotein IIb/IIIa complex and mediates platelet aggregation.

von Willebrand factor (vWF) is necessary for the initial attachment of platelets to exposed subendothelium, particularly under flow conditions like those prevailing in the microcirculation. Little is known about its possible participation in subsequent events leading to formation of platelet thrombi at sites of vascular injury. We addressed this question by studying the mechanisms by which desialylated vWF induces platelet aggregation in the absence of any other stimulus. Asialo vWF, unlike the native molecule, does not require ristocetin to interact with platelets. Agglutination induced by ristocetin is largely independent of active platelet metabolism and only partially reflects physiological events. We have shown here that binding of asialo vWF to platelets was accompanied by release of dense granule content and subsequent ADP-dependent fibrinogen binding to receptors on the glycoprotein (GP) IIb/IIIa complex. The initial interaction of asialo vWF with platelets was mediated by GPIb, as shown by blocking obtained with monoclonal antibody. Inhibition of this initial interaction completely abolished platelet aggregation induced by asialo vWF. The same effect was obtained with a monoclonal anti-GPIIb/IIIa antibody. This, however, did not block asialo vWF binding to platelets, but rather inhibited subsequent fibrinogen binding induced by asialo vWF. Therefore, the latter process was also essential for platelet aggregation under the conditions described. At saturation, asialo vWF induced binding of between 3.2 and 27.7 X 10(3) fibrinogen molecules/platelet, with an apparent dissociation constant between 0.28 and 1.18 X 10(-6) M. This study shows that asialo, and possibly native, vWF acts as a platelet agonist after its binding to GPIb and induces aggregation through a pathway dependent on GPIIb/IIIa-related receptors.

Asialoglycoproteins↗

Red alert.

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Blood Transfusion↗

Quality control.

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Nursing Care↗

Degradative fate of transplanted proteins.

The majority of cell proteins are non-cytosolic and are found in specific extracytosolic cytomorphological sites. Rat liver mitochondria and outer mitochondrial membrane (OMM) vesicles were transplanted homologously into rat hepatocytes and heterologously into rat hepatoma (HTC) cells by polyethylene glycol-mediated organelle--cell or OMM vesicle-cell fusion. The subsequent destructive fate of these non-cytosolic proteins was studied. During culture of hepatocyte monolayers in conditions which give in vivo catabolic rates, the transplanted organelle proteins and monoamine oxidase were degraded at rates similar to in vivo rates, although the transplanted material was not found in the hepatocyte mitochondria. Degradation was preceded by internalization (1-6 h) of the transplanted material and its translocation to a perinuclear, vesicular cytoplasmic position. Prevention of translocation by the disruption of the cytoskeleton inhibited subsequent degradation. In contrast, rat OMM heterologously transplanted into HTC cells was patched, capped and internalized into 'unique' vesicles and degraded 2.5 times faster than in hepatocytes. In both hepatocytes and HTC cells mitochondrial protein degradation was partially susceptible to lysosomotropic agents. The results are discussed in terms of a protein turnover cycle which attempts to coordinate the biochemistry and cell biology of protein synthesis and degradation in eukaryotic cells.

Animals↗

Primary nursing: an evaluation of its effects on patient perception of care and staff satisfaction.

A study evaluating the effects of a system of primary nursing on patients' perception of care and staff satisfaction is described. The study was conducted in a large acute medical-surgical hospital and incorporated a control group and quantitative measures of the variables under investigation. Significantly higher levels of patient and staff satisfaction were shown for the primary nursing unit on items which support the philosophy of primary nursing. Results are compared to previous studies and methodological issues are discussed.

Adult↗

Thoracic duct and right lymphatic duct: surgical approaches for drainage in the canine with comparison of cellular and chemical contents.

The technics of drainage of the right lymphatic duct (RD) and thoracic duct (TD) used in our laboratory have been described and illustrated. In two series of experiments the components of RD and of TD lymph were compared to blood plasma collected concurrently. RD and TD lymph, collected concurrently, were also compared in a third series. RD and TD lymph differ in a number of ways including rate of flow, enzyme activity, cell count and lipid-electrophoretic patterns. The limitations of RD lymph for the study of fluid and protein dynamics of the lungs and the cell population of lung lymph are outlined. Higher levels of enzyme activity in RD compared to TD lymph have been noted. This phenomena appears to depend on a number of complex factors.

Animals↗

A method for the collection of pure pulmonary lymph in the canine.

An original method for the collection of pure or nearly pure pulmonary lymph in the canine is desirable for the study of pulmonary water, protein dynamics and cells. Right lymphatic duct lymph has been used extensively but it known to contain lymph from a number of extrapulmonary sources and has been altered by passage through lymph nodes. Pulmonary lymph was collected from 13 dogs through an open chest. The mean flow of lymph was 1.5 milliliters per hour +/- 0.08. This flow is compared with 3.7 milliliters per hour from the right lymphatic duct and 22.5 milliliters per hour from the thoracic duct in a group of dogs with a closed chest. The levels of lactate dehydrogenase--634 units per liter--and glutamic-oxalacetic transaminase--416 units per liter--in pure pulmonary lymph were much higher than in right lymphatic duct lymph--lactate dehydrogenase 125 units per liter; glutamic-oxalacetic transaminase 94.0 units per liter, in thoracic duct lymph--lactate dehydrogenase 47 units per liter; glutamic-oxalacetic transaminase 80.5 units per liter--and in blood plasma--lactate dehydrogenase 299 units per liter; glutamic-oxalacetic transaminase 95 units per liter. Low levels were noted in Na+, 107, and Cl-, 85, in pure pulmonary lymph versus plasma--Na+ 145; Cl- 112, right lymphatic duct lymph--Na+ 146; Cl- 115, and thoracic duct lymph--Na+ 146; Cl- 114. The method can be adapted for prolonged drainage in conscious dogs, which would enhance its usefulness.

Animals↗

Isolation of three separate anaphylatoxins from complement-activated human serum.

Recent methodologies used in preparing anaphylatoxins from complement-activated serum are described. Activation of the alternative pathway generates C3a and C5a; however, activation of the classical pathway is required to generate the anaphylatoxin from C4. This article describes an activation scheme that simultaneously generates all three of the anaphylatoxins (e.g., C3a, C4a and C5a) in human serum and outlines a procedure for isolating each as homogeneous products. Purification of intact anaphylatoxins directly from complement-activated serum takes place only if an exopeptidase in serum, known as carboxypeptidase N (SCPN), is properly inhibited. A new series of mercapto derivatives of arginine analogs are introduced as potent and effective inhibitors of SCPN. These inhibitors permit normal complement activation but prevent degradation of the released activation fragments C3a, C4a or C5a. The SCPN inhibitor previously used was 6-aminohexanoic acid (EACA), but it required a 1 M concentration for effective inhibition, the substituted mercapto-guanido compounds prove to be effective in the mM range.

Aminocaproic Acid↗