Biomedical subjects

E C Williams

Publications and source records attributed to E C Williams.

At least 19 recordsLinked to original sources

PubMed1996

The discovery of a novel R-phycoerythrin from an antarctic red alga.

A novel biliprotein, named R-phycoerythrin IV, has been discovered. It absorbs blue light better than any other known red algal biliprotein. The protein was found in Phyllophora antarctica, a benthic macroalga, which grows beneath the coastal waters of McMurdo Sound, Antarctica. Fluorescence emission and fluorescence excitation polarization spectroscopy demonstrated that R-phycoerythrin IV behaved as a typical R-phycoerythrin in the functioning of energy migration and has an emission maximum at 577 nm. The circular dichroism (CD) spectrum of the chromophores was compared with visible absorption spectrum, and both were deconvoluted. This process showed the energy states of various individual chromophores. The molecular weight of the protein suggested a alpha6beta6gamma polypeptide structure, and far UV CD studies revealed polypeptides with highly alpha-helical secondary structures. Dynamic light scattering indicated that the protein had a 5.54 nm radius, and its shape was nonspherical. R-phycoerythrin was also purified from a second benthic Antarctic red alga, Iridaea cordata. Its spectroscopic properties were similar to those of some R-phycoerythrins from nonpolar regions. The unique spectroscopic properties of R-phycocerythrin IV may help enable the alga to occupy its niche deeper in the water column than the red alga that has the typical R-phycoerythrin.

Antarctic Regions↗

PubMed1995

PCR amplification of rRNA intergenic spacer regions as a method for epidemiologic typing of Clostridium difficile.

From January to March 1993, a suspected outbreak of antibiotic-associated diarrhea occurred on a pediatric oncology ward of the Clinical Center Hospital at the National Institutes of Health. Isolates of Clostridium difficile obtained from six patients implicated in this outbreak were typed by both PCR amplification of rRNA intergenic spacer regions (PCR ribotyping) and restriction endonuclease analysis of genomic DNA. Comparable results were obtained with both methods; five of the six patients were infected with the same strain of C. difficile. Subsequent analysis of 102 C. difficile isolates obtained from symptomatic patients throughout the Clinical Center revealed the existence of 41 distinct and reproducible PCR ribotypes. These data suggest that PCR ribotyping provides a discriminatory, reproducible, and simple alternative to conventional molecular approaches for typing strains of C. difficile.

Bacterial Typing Techniques↗

PubMed1994

Profile of young people's advice clinic in reproductive health, 1988-93.

For an unprepared sexually active teenager the 1990s present a minefield of potential problems in addition to the most obvious problems of unplanned pregnancy and sexually transmitted disease. Promoting the importance of a healthy sexual and reproductive life to young people requires openness, better sex education, realistic discussion of related issues, and provision of contraception, as well as support if things go wrong. The Woodhouse Park Clinic in south Manchester opened in October 1988 with the aim of providing weekly advice sessions to young people up to the age of 18. Advice is given on topics such as substance misuse and smoking as well as on family planning. Attendance has steadily increased over the years; from April to June 1993 the average number of attenders per session was 39, one third of whom were young men.

Adolescent↗

PubMed1994

Chromophore topography and exciton splitting in phycocyanin 645.

The biliprotein phycocyanin 645 has been purified from a photosynthetic cryptomonad Chroomonas species. It is composed of two copies each of two polypeptides (alpha and beta); each alpha polypeptide has one chromophore, and each beta polypeptide has three. There are one cryptoviolin and two phycocyanobilins on each beta polypeptide and one 697-nm bilin on each alpha polypeptide for a total of eight chromophores on the protein. Circular dichroism (CD) spectroscopy has been used to investigate the arrangement of these chromophores. Comparisons among the intact protein (alpha 2 beta 2) and various urea-treated products have yielded a tentative model for chromophore topography. The six chromophores on the two beta polypeptides are segregated into three pairs. The chromophores of each pair are close enough to experience electronic interactions. One pair, consisting of the two cryptoviolins, produces exciton splitting on the blue edge of the visible CD spectrum, and the two pairs of phycocyanobilins cause exciton splitting on the red edge of this spectrum. Deconvolution shows that the CD spectrum of each pair has a positive and a negative band, which are nearly conservative as expected for exciton coupling. The two chromophores on the alpha polypeptides are more isolated. The pairing of cryptoviolin chromophores occurs across two beta polypeptides, but the more likely position of each of the two pairs of phycocyanobilins is probably not across a beta-beta interface but within a single beta polypeptide. The exciton splitting events both increase the range of visible light absorption for the protein and establish the routes of exciton migration through the protein.

Circular Dichroism↗

PubMed1994

Coronary arteriographic findings in black patients and risk markers for coronary artery disease.

Coronary arteriographic results are reported in 1535 black patients: 751 men (mean age 57 +/- 11) and 784 women (mean age 59 +/- 11). Among the black men 19%, 15%, 21%, and 4% had single-, double-, and triple-vessel and left main disease, respectively. Among the black women there were 12%, 10%, 15%, and 3% with similar involvement. Logistic regression models showed that most of the recognized risk factors were positively correlated with significant (at least one artery with > or = 50% stenosis) coronary disease, but a history of hypertension was not a significant independent predictor in either sex. ECG evidence of previous infarction increased the odds of detecting significant coronary disease by the greatest amount when controlling for other significant risk markers in women. In men both previous infarction and atypical pain (negative) were equally important. This study confirms but does not explain previous reports that have revealed less than expected angiographic evidence of significant coronary artery disease in black compared with white persons.

Analysis of Variance↗

PubMed1993

Alteration of vitronectin. Characterization of changes induced by treatment with urea.

Vitronectin circulates in blood as a 70-kDa monomer that interacts with complexes generated in the terminal steps of the coagulation and complement cascades. Vitronectin complexed to thrombin-antithrombin or C5b-9 is conformationally altered as evidenced by enhanced reactivity with monoclonal antibody 8E6 and binding to heparin; these same alterations also occur when vitronectin is treated with urea (Tomasini, B. R., and Mosher, D.F. (1988) Blood 72, 903-912; Høgåsenk, K., Molnes, T.E., and Harboe, M. (1992) J. Biol. Chem. 267, 23076-23082). We have modified the purifications of native and urea-treated vitronectin to better control conformational state and characterized the alterations induced by urea. After treatment with N-ethylmaleimide to prevent formation of disulfide-linked multimers, purification in 8 M urea, and dialysis against physiological saline, vitronectin was largely oligomeric (approximately 800 kDa) as assessed by gel filtration and polyacrylamide gel electrophoresis in the absence of sodium dodecyl sulfate. Oligomeric urea-treated vitronectin reacted more strongly with the 8E6 antibody, bound biotinylated heparin more strongly, and neutralized the anticoagulant activity of heparin better than monomeric altered vitronectin or native vitronectin. After incubation with urea at 25 degrees C, native vitronectin, treated during purification with dithionitrobenzoic acid to force free sulfhydryls to intramolecular disulfides, exhibited increased reactivity with antibody 8E6, increased binding to heparin, and oligomerization. In addition, incubation in urea caused rearrangement of disulfides as assessed by loss of the light chain of two-chain vitronectin. The transition for these effects occurred between 2 and 4 M urea. Thus, an irreversible conformational alteration occurs upon treatment of vitronectin with urea, resulting in oligomers that bind avidly to heparin.

Antibodies↗

PubMed1992

Anticoagulant effects of sulphonated polyurethanes.

Sulphonated polyurethanes have been shown to have excellent blood contacting properties. In this paper, similar polyurethanes which are water soluble have been investigated to determine their influence on thrombus formation. These polymers were shown to delay clotting times in the following ways: by direct complex formation between the polymer and thrombin; by interference with fibrin polymerization; and by complex interactions between polymer, thrombin, plasma antiproteases and fibrinogen in plasma.

Animals↗

PubMed1992

Neutralization of the anticoagulant effects of glycosaminoglycans by serum amyloid P component: comparison with other plasma and platelet proteins.

Serum amyloid P protein (SAP) is a heparin-binding protein that is found in blood and connective tissues including some types of vascular basement membrane. In this article we present evidence that SAP is capable of blocking the anticoagulant effects of glycosaminoglycans. SAP neutralized the catalytic effect of heparin on the thrombin-antithrombin III reaction more effectively than vitronectin, histidine-rich glycoprotein, fibronectin, and high-molecular-weight kininogen and almost as effectively as platelet factor 4. SAP also blocked the effects of heparin and dermatan sulfate on the inhibition of thrombin by heparin cofactor II. We found evidence for the formation of a high-affinity 1:1 complex between SAP and heparin and for inhibition of binding of both thrombin and antithrombin III to heparin-Sepharose by SAP. We conclude that SAP may account for much of the heparin-neutralizing capacity of plasma under some conditions and that basement-membrane-bound SAP may modulate extravascular coagulation by blocking the anticoagulant effects of basement membrane glycosaminoglycans.

Anticoagulants↗

PubMed1992

Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy.

Adjuvant therapy for breast cancer with tamoxifen is suggested to be of benefit to both women with negative and women with positive axillary nodes, and treatment lasting several years is currently being investigated. Venous thrombophlebitis may complicate tamoxifen treatment at a rate of approximately one per 800 treatment-years. To explore the possible mechanisms of this effect, we evaluated changes in antithrombin III levels, fibrinogen levels, and platelet counts in 140 postmenopausal women with surgically resected breast cancer who were disease free and participating in a double-blind, placebo-controlled, randomized toxicity study of tamoxifen. Antithrombin III levels, elevated at baseline evaluation, decreased in tamoxifen-treated subjects at 6 months, but no subject exhibited a drop to clinically significant levels. Fibrinogen levels decreased 15% (0.4 g/L) in tamoxifen-treated subjects at 6 months. Platelet counts decreased 7% to 9% from baseline to evaluations at 3, 6, 12, 18, and 24 months in tamoxifen-treated subjects. While these changes do not explain the possible small thrombophlebitis-promoting effect of tamoxifen, the decrease in fibrinogen levels might be expected to be associated with a decreased risk of arterial thrombosis.

Antithrombin III↗

PubMed1991

Antiphospholipid antibodies and adrenal hemorrhage.

We recently encountered two cases of massive bilateral adrenal hemorrhage in patients with antiphospholipid antibodies. A search of the records of this institution covering the past 15 years revealed two additional patients with massive adrenal hemorrhage associated with evidence of antiphospholipid antibodies. Three of these four patients were receiving anticoagulant drug therapy. The presence of the antiphospholipid antibodies may increase the risk of massive adrenal hemorrhage, particularly in patients who receive anticoagulant drugs.

Adrenal Gland Diseases↗

PubMed1991

Benign familial thrombocytosis.

A 13-year-old girl was found to have a platelet count in excess of 4 million/microliters while being evaluated for a minor bleeding episode. Her father and two sisters also had thrombocytosis. All four affected patients were asymptomatic and had no clinical or laboratory evidence of a myeloproliferative disorder other than an elevated platelet count. This represents the second reported instance of benign familial thrombocytosis.

Adolescent↗

PubMed1991

Cerebral venous thrombosis with plasminogen deficiency.

We describe a patient with inherited plasminogen deficiency who developed extensive cerebral venous thrombosis. Several other conditions that might have contributed to a hypercoagulable state, including mild thrombocytosis, thyrotoxicosis, and a chronic inflammatory lung disorder, were present. We also discuss the evidence linking plasminogen deficiency with a thrombophilic state. The diagnosis of cerebral venous thrombosis in this case was readily established by nuclear magnetic resonance imaging, a technique that is ideally suited for the evaluation and follow-up of patients with this condition.

Adult↗

PubMed1991

Pilot study of anxiety and depression in prepubertal children.

Early detection of anxiety and depression is important because of the relationship between these disorders, suicide and other problems (i.e. social, phobias, learning problems). This study screened prepubertal students in a school setting for symptoms of anxiety and depression using self-report measures (Revised Children's Manifest Anxiety Scale and the Children's Depression Inventory). Controls and children who scored high on measures of anxiety or depression or both were interviewed with their parents and were tested using the Diagnostic Interview for Children and Adolescents (computer version) and the Peabody Individual Achievement Test. Initial results indicated that anxiety is more prevalent in prepubertal children than depression. The correlation between different diagnostic measurements used in this project was calculated. A correlation was found between low scores of self-esteem and high scores of anxiety and depression on self-reports. It is concluded that self-report measures are good screening tools.

Anxiety↗

PubMed1990

Cerebral venous thrombosis due to heparin-induced thrombocytopenia.

A patient with polycythemia vera who was treated with heparin for superficial septic thrombophlebitis developed heparin-induced thrombocytopenia and cerebral venous thrombosis with superior sagittal sinus occlusion 11 days after the institution of heparin therapy. We suggest that the severe thrombotic response to the heparin-induced platelet disorder in this patient occurred because the polycythemia vera and the purulent infection enhanced the thrombophilia caused by heparin-induced thrombocytopenia. This condition can be avoided in most instances if heparin is used for no longer than 5 days.

Cerebral Veins↗

PubMed1990

Catheter-related thrombosis.

The use of indwelling central catheters for administration of chemotherapy, blood products, and parenteral nutrition is becoming increasingly common. Thrombosis, manifested as formation of either a fibrin sleeve around the catheter or a thrombus adherent to the vessel wall, is a major complication of the use of such catheters. Although frequently asymptomatic, thrombosis may cause catheter occlusion, vascular obstruction, septic phlebitis, or pulmonary embolism. The pathophysiology and management of catheter thrombosis are discussed.

Animals↗

PubMed1989

Plasma alpha 2-antiplasmin activity. Role in the evaluation and management of fibrinolytic states and other bleeding disorders.

To determine the clinical significance of acquired alpha 2-antiplasmin deficiency in patients with bleeding disorders, I reviewed the results of assays performed on 184 patients over a 4-year period. Thirty-two evaluable patients had alpha 2-antiplasmin activity levels of less than 50% of normal (defined as severe deficiency), and 35 patients had levels between 50% and 75% of normal (mild deficiency). Records of these patients and of 32 patients who had normal levels were reviewed. Most patients with severe alpha 2-antiplasmin deficiency had either liver disease or disseminated intravascular coagulation and/or fibrinolysis, or both. There was a high incidence of severe alpha 2-antiplasmin deficiency among patients with acute promyelocytic leukemia. Five patients with pathologic bleeding had no identifiable coagulation abnormalities other than alpha 2-antiplasmin deficiency. The group with severe alpha 2-antiplasmin deficiency had a significantly higher incidence of life-threatening or fatal bleeding and the most striking laboratory evidence of hyperfibrinolysis. Using the presence of severe alpha 2-antiplasmin deficiency as an indication for therapy, epsilon-aminocaproic acid treatment was associated with cessation of life-threatening bleeding in 8 of 11 patients.

Adolescent↗

PubMed1988

Identification of a new hereditary amyloidosis prealbumin variant, Tyr-77, and detection of the gene by DNA analysis.

In the last several years, five human plasma prealbumin (transthyretin) variants have been discovered in association with hereditary amyloidosis, a late-onset fatal disorder. We recently studied a patient of German descent with peripheral neuropathy and bowel dysfunction. Biopsied rectal tissue contained amyloid that stained with anti-human prealbumin. Amino acid sequence analysis of the patient's plasma prealbumin revealed both normal and variant prealbumin molecules, with the variant containing a tyrosine at position 77 instead of serine. We predicted a single nucleotide change in codon 77 of the variant prealbumin gene, which we then detected in the patient's DNA using the restriction enzyme SspI and a specifically tailored genomic prealbumin probe. DNA tests of other family members identified several gene carriers. This is the sixth prealbumin variant implicated in amyloidosis, and adds to the accumulating evidence that the prealbumin amyloidoses are more varied and prevalent than previously thought.

Amyloidosis↗

PubMed1987

Inhibition of fibrin polymerization by serum amyloid P component and heparin.

The effects of serum amyloid P component (SAP) and heparin on the thrombin-catalyzed formation of polymeric fibrin from purified fibrinogen were examined using a turbidometric method to quantify fibrin polymerization. SAP and heparin acted synergistically to inhibit the lateral aggregation of fibrin fibrils, resulting in the formation of fibrils with a smaller mass to length ratio. Heparin did not enhance the incorporation of SAP into fibrin clots, and the effect of heparin and SAP did not seem to be related to inhibition of thrombin or of fibrinopeptide release. The evidence suggests that a soluble complex of SAP and heparin inhibits fibrin polymerization.

Calcium↗