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Somatic hypermutation in antoimmune thyroid disease (1998)

Mclntosh, Richard ; Watson, Philip ; Weetman, Anthony

Oxford, UK : Blackwell Publishing Ltd

Immunological reviews 162 (1998), S. 0

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ISSN: 1600-065X

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Medicine

Notes: Summary: Autoimmune thyroid disease is one of the most common autoimmune diseases. There is typically patient antibody (Ab) reactivity to one or more of the antigens thyroglobulin (Tg), thyroid peroxidase (TPO) and the thyroid stimulating hormone receptor (TSFlr). With the advent of combinatorial library technology, there has been an enormous increase in the number of sequences from Ab to Tg and TPO, The repertoire of both Tg and TPO Ab is restricted and indicates the importance of somatic hypermutation in the development of the high affinity, Ab response. However, there are still too few sequences to determine patterns in which the mutation occurs, which residues are introduced during substitution and how individual substitutions affect the affinity of the Ab, Ab to the TSHr are of far greater pathological significance than those to Tg and TPO, but the current repertoire of Ab to the TSHr has yet to include the high affinity IgG Ab characteristic of patient serum Ab, Instructive analysis of the role of somatic hypermutation in the development of TSHr Ab therefore still awaits the isolation of the pathologically active repertoire. Despite this, the Ab response in thyroid autoimmunity remains one of the best characterised of human autoimmune diseases.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1111/j.1600-065X.1998.tb01444.x

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Pharmacokinetics of a Hematoregulatory Peptide (SK&F 107647) in Healthy Male Volunteers and in Patients with Colorectal or Pancreatic Adenocarcinoma Not Amenable to Standard Therapy (2000)

Zia-Amirhosseini, Parnian ; Harris, Robert Z. ; Cowley, Hugh C. ; [et al.]

Springer

Pharmaceutical research 17 (2000), S. 385-390

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ISSN: 1573-904X

Keywords: SK&F 107647 ; peptide ; pharmacokinetics ; hematore gulatory ; adenocarcinoma ; cytokines

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract Purpose. To describe the pharmacokinetics of SK&F 107647, a synthetichematoregulatory peptide, in healthy volunteers and in patientswith adenocarcinoma.Methods. SK&F 107647 pharmacokinetics were evaluated in 2dose-escalation studies. Volunteers received SK&F 107647 as single15-minute iv infusion doses of 1, 10, 100, 500, and 1000 μg/kg. Cancerpatients received 2-hour iv infusions of 0.001, 0.01, 0.1 and 1μg/kg once daily for 10 days. Drug concentrations were quantified in plasmaand urine of healthy volunteers and on days 1 and 10 in plasma ofcancer patients receiving the two top dose levels.Results. In volunteers, mean clearance (CL) ranged from 76.7 to 101ml/hour/kg; mean volume of distribution at steady-state (Vss)rangedfrom 175 to 268 ml/kg. Most of the administered dose was renallyexcreted as intact peptide within 24 hours postinfusion. In patients,mean CL was 57.6 ml/hour/kg, mean Vss ranged from 128 to 150ml/kg and terminal half-life from 2.1 to 3.4 hours. There was littleaccumulation of drug. In both studies, linear pharmacokinetics wasobserved. Clearance approached normal glomerular filtration rate(GFR) in volunteers and correlated with creatinine clearance incancer patients.Conclusions. SK&F 107647 exhibits linear pharmacokinetics, a smallVss, and clearance, primarily renal, approaching normal GFR.