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Biomedical subjects

W R Bell

Publications and source records attributed to W R Bell.

At least 109 records · Page 6Linked to original sources
PubMed1984

Direct spectrophotometry of serum hemoglobin: an Allen correction compared with a three-wavelength polychromatic analysis.

An Allen correction and a polychromatic analysis are about equally effective in minimizing effects of interference by bilirubin and triglyceride turbidity in the direct spectrophotometry of serum hemoglobin: interference from bilirubin is nearly eliminated, that from turbidity substantially decreased. The limit of detectability of hemoglobin is 8 mg/L in the presence of a moderate concentration of bilirubin. A change in hemoglobin concentration as small as 16 mg/L can be detected in serum having a concentration near the upper limit of the reference interval, i.e., at the medical decision level. The polychromatic formula gives concentration estimates approximately 5% greater than those of the Allen correction. The formula for the Allen correction is hemoglobin (mg/L) = 1.68 mA415 - 0.84 mA380 - 0.84 mA450 . That for the polychromatic analysis is hemoglobin (mg/L) = 1.65 mA415 - 0.93 mA380 - 0.73 mA470 .

Bilirubin↗
PubMed1983

The human plasmin-derived light (B) chain X streptokinase complex: a second-generation thrombolytic agent.

Specific assay methods for the human plasmin-derived light (B) chain X streptokinase (B X SK) complex, in terms of both streptokinase (SK) and urokinase (UK) International Units, are described. The kinetic properties of various SK activator complexes with plasminogen, Val442-plasmin, and the plasmin-derived light (B) chain were compared to SK in terms of their catalytic efficiencies and Lineweaver-Burk plots. Similar kinetic data, and Lineweaver-Burk plots, are described for both highly purified high-molecular weight UK and low-molecular weight UK, including different clinical UK preparations. The B X SK complex has the highest catalytic efficiency of all the activator species studied. The Lineweaver-Burk plots of each of the various activator species are "fingerprints" of the enzymatic character of the activator. The B X SK complex is more like UK than SK, as an activator, in activating non-human plasminogen species. The biological half-life of the B X SK complex, in a dog model, was determined to be about 4 hr which is longer than the biological half-life(s) of SK in the same animal model, namely 0.6 hr (47%) and 2.8 hr (53%). This new second-generation activator complex may prove to be a useful thrombolytic agent in the treatment of thromboembolic diseases.

Animals↗
PubMed1983

Binding and endocytosis of glycoproteins and neoglycoproteins by isolated rabbit hepatocytes.

Rabbit hepatocytes were isolated by a collagenase perfusion technique, and used to study the binding and endocytosis of the glycoprotein, asialo-orosomucoid, and the neoglycoprotein, Gal39-bovine serum albumin. Both of these proteins contain exposed galactosyl residues, and were avidly bound by the lectin on the hepatic parenchymal cell surface. Steady state and kinetic experiments performed at 2 degrees C and at 37 degrees C revealed the presence of two apparent classes of binding sites totalling 4.7 X 10(5) sites/cell at 2 degrees C, and 6.3 X 10(5) sites/cell at 37 degrees C. At 37 degrees C, both classes of sites participated in internalization of bound ligand. The cells were capable of internalizing about 60 000 molecules/min per cell. The process appeared to be first-order, with a rate constant k = 0.098 min-1 and t1/2 = 7.1 +/- 0.6 min. Binding could be inhibited by galactose-containing compounds, EGTA, and by anti-(hepatic lectin) immunoglobulin G. The inhibition by antibody appeared to be reversible upon removal of antibody-containing medium.

Animals↗
PubMed1983

Unexplained hemolytic anemia associated with pregnancy.

Unexplained hemolytic anemia in pregnancy is a rare condition. Striking anemia beginning in the first (38%) or second (38%) trimester, resolving within 5 months of delivery (18 of 19 patients, 95%) and recurring in a subsequent pregnancy (six of 12 patients, 50%) was noted in a total of 19 pregnancies in 12 women. Transient hemolysis was present in four of 19 (22%) infants. The etiology of this problem is unknown, and the only factor clearly associated with the anemia is the gravid state. Characteristic of this problem is the absence of any identifiable immune mechanism or intracorpuscular or extracorpuscular defects despite the use of specific and sensitive complement-fixation antibody consumption techniques and assay of all red blood cell enzymes. Important in the management of these patients is the clinical observation that they do respond (seven of seven patients) to corticosteroid therapy and can experience a normal delivery. Although not frequent, this problem can be life threatening to both mother and child. With early recognition and appropriate treatment with corticosteroids the hazards of this condition can be avoided.

Adult↗
PubMed1983

Abnormalities of the spleen and liver in patients with hemophilia.

Previous studies have demonstrated functional and histologic abnormalities of the liver, and, more recently, splenomegaly in patients with hemophilia. Since these observations usually were derived from hemophiliacs who had received intensive replacement therapy, the question was posed as to whether the frequency of splenic and hepatic abnormalities was secondary to the amount of therapy utilized. In this study, a variety of tests were employed to evaluate spleen and liver size and function to determine if abnormalities in these organs correlated with the intensity of the transfusion program. The study group was comprised of 25 hemophiliacs (mean factor replacement-18,361 U/year; median factor replacement-12,920 U/year). Over 70% of our patients had elevations of aspartate and alanine aminotransferase. Immunoglobulin and complement levels were normal in most subjects. Ninety-six percent had evidence of exposure to hepatitis B virus. Liver-spleen imaging suggested significant hepatic abnormalities in most of the patients as evidenced by inhomogeneity of tracer uptake in the liver in 33% and relatively increased colloid uptake in the spleen in 90%. Splenomegaly (palpable spleen or enlargement on liver-spleen imaging) was detected in 40% of our patients, and tended to occur in the more frequently transfused patients. These findings indicate that significant abnormalities of the spleen and liver can occur in hemophiliacs who have received moderate amounts of replacement therapy and that liver-spleen imaging may be a useful method for monitoring the development of hepatic and splenic abnormalities.

Adolescent↗
PubMed1983

Fibrinogen Baltimore II: congenital hypodysfibrinogenemia with delayed release of fibrinopeptide B and decreased rate of fibrinogen synthesis.

A congenital hypodysfibrinogenemia, fibrinogen Baltimore II, was found in a young asymptomatic Caucasian female. Prothrombin, partial thromboplastin, and euglobulin lysis times were normal, as were platelet function and coagulation factor assays. Subnormal plasma fibrinogen levels were found using chronometric, rate-independent, and immunologic assay methods. Kinetic analysis of fibrinopeptide release revealed a delay in the thrombin-catalyzed release of fibrinopeptide B from the abnormal protein. Proteolysis of fibrinopeptide A by thrombin or Arvin, fibrin monomer polymerization, and fibrin polymer ligation occurred at normal rates. Catabolism of radiolabeled autologous and homologous fibrinogen was also normal, but the fibrinogen synthetic rate was less than half the normal value. Comparison of the coagulation characteristics of fibrinogen Baltimore II with those of other abnormal fibrinogens indicates that it represents a unique example of hypodysfibrinogenemia.

Adult↗
PubMed1983

Stimulation of fibrinogen biosynthesis by fibrinogen fragments D and E.

Infusions of either fibrinogen fragment D or fibrinogen fragment E into rabbits were followed by increases in fibrinogen synthesis determined by the rate of incorporation of 75Se-selenomethionine into circulating fibrinogen. The degree of stimulation was proportional to the amount of protein infused. When 4.5 mg of each fibrinogen fragment was administered separately to different groups of animals, fibrinogen fragment D was associated with a fourfold increase in fibrinogen synthesis above that in the control animals compared with 1.5-fold increase induced by fragment E. Fragments D and E were assayed for bound sialic acid, the absence of which facilitates binding, transport and catabolism of many circulating glycoproteins by the liver. Fibrinogen fragment D contained 1.3% sialic acid compared to 1.4% in fragment E. These data indicate conservation of sialic acid during plasmic digestion of fibrinogen. The capacity of these glycopolypeptide fragments to stimulate fibrinogen synthesis appears unrelated to the nearly identical quantities of N-acetyl neuraminic acid found in each fragment.

Animals↗
PubMed1983

Coagulation properties of intraocular humors and cerebrospinal fluid.

Clinical observations indicated a prompt cessation of episcleral capillary bleeding after exposure of those tissues to aqueous humor during intraocular surgery. Based on this observation, both aqueous and vitreous humors were obtained from eyes provided by an eye bank and from human eyes prior to intraocular surgery. Samples of cerebrospinal fluid also were obtained from two patients, one with optic atrophy and another with nutritional amblyopia. A total of 49 specimens were studied. Aqueous humor shortened the average ear lobe puncture bleeding time from 4.74 +/- 0.2 to 1.13 +/- 0.1 minutes. Varying dilutions of aqueous humor, up to a dilution of 1:16, shortened prothrombin and partial thromboplastin times when compared with normal control plasma without aqueous. Vitreous humor shortened partial thromboplastin time but had no effect on prothrombin time. The effect of cerebrospinal fluid on prothrombin and partial thromboplastin times was similar to the aqueous, but to a lesser degree.

Aqueous Humor↗
PubMed1982

Carbohydrate structure of human fibrinogen. Use of 300-MHz 1H-NMR to characterize glycosidase-treated glycopeptides.

The carbohydrate composition of fibrinogen and constituent S-carboxymethylated chains was determined. All the carbohydrate on the parent molecule could be accounted for on the B beta and gamma chains. The A alpha chain was found to be devoid of carbohydrate. Glycopeptides were prepared from fibrinogen, B beta, and gamma chains by pronase digestion and subsequent chromatography on Sephadex G-50. The 300-MHz 1H-NMR spectra of glycopeptides from all three sources were consistent with biantennary type oligosaccharide chains. The glycopeptides resulting from exoglycosidase digestions were examined with 300-MHz 1H-NMR spectroscopy, and the changes in the signals caused by selective removal of sugar residues were studied. This technique enabled us to assign each anomeric proton to the corresponding monosaccharide unit independent of previous work. Our results indicate that fibrinogen glycopeptides are of the biantennary type, and are in complete agreement with the previously reported peak assignments (Vliegenthart, J. F. G., van Halbeek, H., and Dorland, L. (1981) Pure Appl. Chemn. 53, 45-77). Affinity chromatography of the glycopeptides on concanavalin A-Sepharose also showed that the glycopeptides from fibrinogen are greater than 95% biantennary oligosaccharide chains. Based on carbohydrate composition, 1H-NMR spectroscopy, sequential exoglycosidase digestion, and gas chromatography-mass spectrometry of derived partially methylated alditol acetates, we propose that fibrinogen contains four oligosaccharide chains of the structure shown below. (formula, see text)

Carbohydrate Sequence↗
PubMed1982

Binding and endocytosis of cluster glycosides by rabbit hepatocytes. Evidence for a short-circuit pathway that does not lead to degradation.

Synthetic cluster glycosides containing either one, two, or three galactosyl or lactosyl residues per ligand were used to test the effect of carbohydrate clustering on binding by the rabbit hepatic Gal/GalNAc-binding lectin using either isolated rabbit hepatocytes or the solubilized, affinity-purified lectin. The tris- and bis-glycosides were superior to the mono-glycosides for inhibition of 125I-asialoorosomucoid binding to rabbit hepatocytes at 0 degrees C. The concentrations of the tris-glycosides required for 50% inhibition of 125I-asialoorosomucoid binding (4-8 microM) to hepatocytes were 50-100 times lower than the concentrations of the corresponding mono-glycosides required for 50% inhibition (400-500 microM). The isolated lectin, however, did not effectively discriminate between the mono-, bis-, and tris-glycosides, possibly indicating an organizational difference between the lectin in the cell membrane and the isolated lectin. When the cluster glycosides were labeled with 125I-tyrosine, it was shown that the tris- and bis-galactosides were bound to the hepatocytes at 37 degrees C, and that binding was followed by a step that led to ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid resistance, probably internalization. The process could be specifically inhibited by the neoglycoprotein Gal44-AI-bovine serum albumin, or by IgG specific for the hepatic lectin, but not by preimmune IgG. Internalization of the cluster glycosides did not lead to accumulation of ligand inside the cell, nor to degradation. Instead, the ligands were quickly released from the cells.

Animals↗
PubMed1981

Diagnosis and treatment of anticoagulant-related adrenal hemorrhage.

Anticoagulant-related adrenal hemorrhage, as a cause of adrenal insufficiency, is rarely suspected and diagnosed during life. We report three patients in whom prompt diagnosis allowed successful treatment with replacement doses of corticosteroids. In all three patients, a hypotensive episode preceded the signs and symptoms of acute adrenal insufficiency. The symptoms and signs of adrenal hemorrhage were nonspecific and variable, making clinical diagnosis difficult. In none of our patients was the prothrombin time, partial thromboplastin time, or Lee White clotting time prolonged beyond the therapeutic range, and in none were excessive doses of anticoagulant therapy employed. Characteristic serum chemistry abnormalities, serum ACTH stimulation tests, and daily urinary collections for free cortisol, 17-OH ketosteroids, and 17-ketosteroids confirmed the clinical suspicion of primary adrenal insufficiency in all cases. Diagnosis was aided in one patient by abdominal computerized axial tomographic scan. In all patients, response to replacement doses of corticosteroids was prompt and gratifying, underlining the importance of suspecting this complication of anticoagulant therapy and instituting prompt lifesaving therapy. Adrenal hemorrhage is a complication of anticoagulant therapy that has been diagnosed during life in only 11 reported cases. We describe three patients in whom early diagnosis allowed prompt medical therapy and favorable outcome. The clinical presentation, diagnostic laboratory features, and therapeutic modalities are reviewed. Prolongation of prothrombin time, high levels of stress, and hypotension predispose to this complication in a patient maintained on anticoagulant therapy.

Adrenal Gland Diseases↗
PubMed1981

Acanthocytosis and haemolytic anaemia due to the McLeod blood group.

A fourteen-year-old boy presenting with marked acanthocytosis of the red blood cells and a compensated haemolytic anaemia was shown to have the McLeod blood type. Only three other individuals have been reported as having this abnormality of the Kell blood group system without evidence of chronic granulomatous disease. Serological typing for the McLeod phenotype should be undertaken in males with unexplained acanthocytosis, and CPK estimation may provide a screening test for this condition.

Acanthocytes↗