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Biomedical subjects

S W Hall

Publications and source records attributed to S W Hall.

At least 37 records · Page 2Linked to original sources
PubMed1989

Binding of bovine, ovine, porcine, canine, and rat plasminogen to rat hepatocytes and rat C6 glioma cells in vitro.

Plasminogens were purified by affinity chromatography from bovine, ovine, porcine, canine, and rat plasma. The binding of each plasminogen to rat hepatocytes in primary culture and to rat C6 glioma cells was studied by radiodisplacement experiments. All of the plasminogens inhibited human 125I-[Glu1]plasminogen type 2 binding to specific cell surface receptors. The IC50 values were similar. These studies suggest conservation of the receptor recognition site in plasminogens across species lines.

Animals↗
PubMed1989

Expression of plasminogen receptors on C6 glioma cells.

Plasminogen activators (PAs) play an important role in normal and neoplastic neuromorphogenesis in the central nervous system. Proper function of proteinases such as PA may require focusing of activity on a cellular level. In this study, we demonstrate that highly purified plasminogen binds to receptors on rat C6 glioma cells in culture. Specific binding is reversible and saturable at 4 degrees C. The Kd is 1.95 +/- 0.31 microM and the Bmax is 3.6 x 10(6) molecules/cell. At 37 degrees C, there is no evidence for ligand digestion or internalization. Plasminogen receptors may concentrate potential proteinase near membranes of glia during normal and neoplastic development in the central nervous system.

Animals↗
PubMed1989

Solid phase extraction of the zwitterionic detergent chaps.

Multiple techniques for solid phase adsorption of 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) were evaluated. Both the porous polystyrene divinylbenzene matrices (BioBeads SMTM) and Extracti GelTM D reduced CHAPS to significantly below its critical micellar concentration while Extracti-GelTM removed CHAPS to below detectable limits. Bio-Bead extraction of CHAPS correlated with the surface area of the bead type. SM-16 beads, with the largest effective surface area, removed nearly 97% of the detergent. For a given amount of detergent and mass of Bio-Beads, the ratio of sample to total bead volume significantly affected CHAPS adsorption. Total protein recovery with the Extracti-GelTM was approximately 97%. Protein recovery in the samples treated with Bio-Beads varied from 56-95%. Chromatographic rather than batch processing yielded optimum recoveries. CHAPS can be effectively removed from dilute protein solutions by solid phase adsorption and this technique offers significant advantages over standard dialysis or gel filtration methods.

Adsorption↗
PubMed1989

Pragmatic procedures for detecting and documenting alcoholism in medical patients.

Although alcoholics are known to utilize a disproportionate amount of medical care, hospital patients are not routinely screened for alcoholism. A sample of 310 randomly selected patients from two hospitals were administered a structured diagnostic interview. More than one-third (35%) of the men and 14% of the women met DSM-III criteria for a current alcohol use disorder and an additional 27% of the men and 9% of the women met criteria for an alcohol use disorder in remission. The practicality and efficiency of structured interviews is discussed along with the potential of a small subset of items to serve as a screen for alcoholism.

Alcoholism↗
PubMed1986

Purification and properties of guanylate kinase from bovine retinas and rod outer segments.

The presence of three soluble nucleotide phosphotransferases in bovine rod outer segments was demonstrated: guanylate kinase (EC 2.7.4.8), nucleoside-diphosphate kinase (EC 2.7.4.6) and adenylate kinase (EC 2.7.4.3). The enzyme guanylate kinase, which catalyzes the reaction GMP + ATP in equilibrium GDP + ADP, was purified to homogeneity from isolated bovine rod outer segments as well as from bovine retinas. The enzyme preparations obtained from both sources are identical in their chromatographic properties, molecular mass (20-23 kDa for both native enzyme and dodecylsulfate-denatured polypeptide), Km values (13 microM for GMP and 430 microM for ATP), specific activities, and nucleotide specificities. The enzyme's turnover number was estimated to be 130 s-1. The minimum amount of enzyme found in rod outer segments is about 1 copy per 800 rhodopsin molecules. The role of the enzyme in the cyclic GMP cycle in rod outer segments is discussed.

Adenosine Triphosphate↗
PubMed1986

Phosphodiesterase activation by photoexcited rhodopsin is quenched when rhodopsin is phosphorylated and binds the intrinsic 48-kDa protein of rod outer segments.

Each photoexcited rhodopsin (R*) molecule catalyzes binding of GTP to many copies of the guanine nucleotide-binding protein transducin, which, in its GTP-binding form, then activates cGMP phosphodiesterase (PDEase). Subsequent deactivation of this light-activated enzyme cascade involves hydrolysis of the GTP bound to transducin, as well as decay of the activating capacity of R*. We report here that deactivation of PDEase in rod outer segment suspensions is highly enhanced by addition of ATP and purified 48-kDa protein, which is an intrinsic rod outer segment protein that is soluble in the dark but binds to photolyzed rhodopsin that has been phosphorylated by rhodopsin kinase and ATP [Kühn, H., Hall, S.W. & Wilden, U. (1984) FEBS Lett. 176, 473-478]. To analyze the mechanism by which ATP and 48-kDa protein deactivate PDEase, we used an ATP-free system consisting of thoroughly washed disk membranes, whose rhodopsin had been previously phosphorylated and chromophore-regenerated, and to which purified PDEase and transducin were reassociated. Such phosphorylated membranes exhibited a significantly lower (by a factor less than or equal to 5) light-induced PDEase-activating capacity than unphosphorylated controls. Addition of purified 48-kDa protein to phosphorylated membranes further suppressed their PDEase-activating capacity; suppression could be as high as 98% (as compared to unphosphorylated membranes), depending on the amount of 48-kDa protein and the flash intensity. Addition of ATP had little further effect. In contrast, PDEase activation or deactivation with unphosphorylated control membranes was not influenced by 48-kDa protein, even in the presence of ATP, provided rhodopsin kinase was absent. Our data suggest that 48-kDa protein binds to phosphorylated R* and thereby quenches its capacity to activate transducin and PDEase.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1985

Trials of staphylococcal protein A-treated plasma infusions in cancer therapy: clinical effects and implications for mode of action.

The data presented here indicate that patients with advanced cancer exhibit a modest but definite objective response rate to biweekly infusions of autologous plasma treated with purified, covalently bound staphylococcal protein A in a relatively nontoxic treatment program. The possibility that responses could be enhanced by alteration of treatment parameters, improved patient selection, and/or combined therapy remains to be explored. In vitro studies indicate that tumor cell killing can be produced in an ovarian cancer cell line using ascitic fluid of some ovarian cancer patients that has been treated with small amounts of protein A covalently linked to silica gel or agarose. This may be a suitable model system for exploration of possible humoral mechanisms of protein A-associated tumoricidal effects. The available literature indicates an antitumor effect of protein A-treated patient plasma in a variety of in vitro systems, as well as in animal and human tumors in vivo. Preliminary investigations of the mechanism of these effects are inconsistent and support the view that several different mechanisms of tumor cell killing may be operative in different settings.

Adult↗
PubMed1984

Light-induced binding of 48-kDa protein to photoreceptor membranes is highly enhanced by phosphorylation of rhodopsin.

The 48-kDa protein, a major protein of rod photoreceptor cells, is soluble in the dark but associates with the disk membranes when some (5-10%) of their rhodopsin has absorbed light and if this rhodopsin is additionally phosphorylated by ATP and rhodopsin kinase. If rhodopsin has been phosphorylated and regenerated prior to the protein binding experiment, the binding of 48-kDa protein depends on light but no longer on the presence of ATP. Another photoreceptor protein, GTP-binding protein, associates with both phosphorylated and unphosphorylated rhodopsin upon illumination. Excess GTP-binding protein thereby displaces 48-kDa protein from phosphorylated disks; this indicates competition between these two proteins for binding sites on illuminated phosphorylated rhodopsin molecules.

Adenosine Triphosphate↗
PubMed1983

Clinical pharmacology of the anticancer polypeptide neocarzinostatin.

The clinical pharmacology of the anticancer polypeptide neocarzinostatin was studied in 16 patients with disseminated neoplasia using a radioimmunoassay technique. Patients who received 2,400-3,600 U of the drug per square meter BSA by rapid IV infusion had triphasic plasma decay curves. For eight patients with normal hepatic and renal function, neocarzinostatin mean plasma half-lives were 0.14, 0.50, and 7.7 h. The mean plasma drug clearance was 32.4 ml/min/m2 and the apparent volume of distribution 19.3 l/m2. Two patients with liver dysfunction had shorter terminal plasma half-lives and greater drug clearance, while two with renal disease exhibited prolonged plasma half-lives and reduced drug clearances. The mean cumulative urinary excretion of neocarzinostatin was 69.1% of the administered dose at 72 h in three patients with normal hepatic and renal function. One patient with liver disease excreted 90.4%, while a patient with renal disease excreted only 58.1% of the dose in 24 h. In one patient with marked liver disease, biliary excretion accounted for 0.1% of the administered dose in 72 h. Cerebrospinal fluid concentrations of neocarzinostatin studied in two patients showed a CSF penetration of about 16% the plasma concentration at 1-5 h; concentrations persisted for 19 h in one patient with an Omayha reservoir. Neocarzinostatin was rapidly cleared from the plasma and eliminated in the urine. Dosage reductions of 50% are recommended for patients with impaired renal function, while no reduction or escalated doses could be tolerated by patients with liver disease. The pharmacologic data suggest a continuous IV infusion may be a more toxic but perhaps more effective schedule of administration.

Adult↗
PubMed1983

Treatment of advanced malignancy with plasma perfused over staphylococcal protein A.

A total of 14 extensively pretreated patients with advanced and progressive malignancy were given 140 infusions of autologous plasma that had been perfused over staphylococcal protein A bound to an agarose gel (Sepharose). Infusions ranged in volume from 35 ml to 260 ml (mean, 70 ml), and the quantity of protein A used ranged from 1 to 30 mg per 100 ml of plasma (mean, 10 mg). Acute toxic reactions included fever (21%), chills (18%), nausea (17%), vomiting (8%), pain (9%) and bronchospasm (2%). Four patients did not have an acute toxic reaction and no chronic or cumulative toxic effects were identified. In two patients there was objective tumor regression and in five there was stabilization of disease lasting from 4 to 12 weeks. Further study of this treatment modality is warranted.

Adult↗
PubMed1983

Human pharmacokinetics of a new acridine derivative, 4'-(9-acridinylamino)methanesulfon-m-anisidide (NSC 249992).

The clinical pharmacology of 4'-(9-acridinylamino)methanesulfon-m-anisidide (amsacrine) was studied, utilizing [9-14C]amsacrine i.v. in 19 patients with disseminated neoplasms. The mean terminal plasma half-life for total 14C ranged from 34 hr in patients with normal organ function to 46 hr in patients with severe liver disease. For unchanged amsacrine, the mean values of plasma half-life were 7.4 and 17.2 hr for patients with normal and abnormal liver function, respectively. The plasma half-lives of 14C were prolonged, while those for unchanged amsacrine appeared to be normal in patients with renal dysfunction. The mean 72-hr cumulative urinary excretion of total 14C varied from 35% in normal patients to 49% in patients with severe liver disease, while patients with renal disease excreted only 2 to 16%. In comparison, the urinary excretion of unchanged amsacrine was 12, 20 and 2% of the administered dose, respectively, in these same patients. Amsacrine biliary excretion studied in two patients showed about 8 and 36% of the administered radioactivity excreted in the bile in 72 hr, with less than 2% as unchanged amsacrine. Cerebrospinal fluid concentrations of amsacrine were below 2% of the simultaneous plasma levels in three patients. Impaired amsacrine drug clearance was frequently associated with liver dysfunction. Patients with impaired amsacrine drug clearance experienced the most severe clinical toxicity. Hepatic metabolism and biliary excretion appear the most important routes for amsacrine elimination. Renal elimination, although less important, is significant in patients with severe kidney dysfunction. To avoid excessive clinical toxicity, initial dose reductions of 30 to 40% are recommended for patients with severe liver or renal disease or for those who have pharmacologically documented impaired drug clearance.

Aminoacridines↗
PubMed1982

Bleomycin clinical pharmacology by radioimmunoassay.

Bleomycin pharmacokinetics were studied by radioimmunoassay in 11 patients who received 7-30 U intravenously (IV) and eight patients who received 4-30 U subcutaneously (SC). For patients who received IV bleomycin plasma disappearance was biphasic, with a mean initial half-life of 0.26 h and a terminal half-life of 2.3 h. Mean plasma drug clearance was 67.8 ml/min/m2 and the volume of distribution was 13.2 l/m2. Urinary excretion accounted for 63.9% of the drug in 24 h. After SC administration peak plasma levels occurred in 1.1 h, with a mean elimination half-life of 4.3 h. Mean plasma drug clearance was 60.5 ml/min/m2 and the volume of distribution was 19.2 l/m2. Bleomycin plasma clearance correlated well with serum creatinine (r2 = 0.72). Bleomycin has a rapid plasma elimination and urinary excretion. Bleomycin bioavailability after SC administration appears comparable to that seen after IV administration as determined by the areas under the plasma disappearance curves. Prolonged plasma levels are seen after SC injection, suggesting this route of administration can produce plasma concentrations comparable to those attained with continuous IV infusions.

Adolescent↗
PubMed1982

Doxorubicin-DNA complex: a phase I clinical trial.

Thirty-five patients with advanced malignancies were treated with doxorubicin-DNA complex in a phase I clinical trial. The patients ranged in age from 30 to 77 years (median, 51) and received doxorubicin-DNA in doses that ranged from 20 to 135 mg/m2. Of the doses administered, 73% were 60-90 mg/m2 (median, 60). Nonhematologic toxic effects included nausea and vomiting in 32% of the patients, fever and chills in 24% mucositis in 18%, and decreases in ECG QRS voltage of greater than 30% in 18%. Fever of unknown origin was seen in 26% of the patients, with documented infection in 9%; 6% had drug-related deaths. All patients experienced alopecia. Hematologic toxic effects (median day, Day 14) included median granulocyte count nadirs of 0.8 X 10(3)/microliter at a 60-mg/m2 dose and 0.3 X 10(3)/microliter at 75 mg/m2. Thrombocytopenia was less severe, with median nadir counts of 131,000 cells/microliter at a 60-mg/m2 dose on median day. Day 13. Treatment courses could be repeated every 3 weeks. Clinical responses (complete plus partial) were seen in 12% of the patients, with an additional 48% showing stable disease. No patients entered in the study were known to be doxorubicin-resistant. Based on these data, we recommend a starting dose of 60 mg/m2 in patients with adequate bone marrow reserve and 50 mg/m2 in those with compromised bone marrows. Doxorubicin-DNA exhibits major clinical toxic effects on the gastrointestinal and hematopoietic systems, with dose-limiting granulocytopenia.

Adult↗