Isolation of an abnormal protein C molecule from the plasma of a patient with thrombotic diathesis

Protein C has been purified from the plasma of a patient with thrombotic diathesis. Both before and after isolation, the protein showed reduced capacity to hydrolyze synthetic substrates and to anticoagulate plasma. Proteolysis with the soluble thrombin- thrombomodulin complex proceeded normally and to completion as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Approximately one-third of the protein is functional, indicating a heterozygous defect. Indirect studies suggest that the abnormal component can bind to protein S and phospholipids. Both forms of activated protein C can also incorporate radiolabeled diisopropylfluorophosphate.     

Urinary-derived Monocyte-Colony Stimulating Factor (P-100) following treatment with carboplatin and etoposide in small cell lung cancer (SCLC)

Background: The hematopoietic growth factor P-100 is a monocyte-colonystimulating factor purified from human urine and has been reportedto reduce neutropenia following chemotherapy. In this studythe effect and toxicity of P-100 was evaluated in 26 patientsreceiving intensive chemotherapy for SCLC. Study design: Chemotherapy consisted of four 28 day cycles ofcarboplatin (C) 600 mg/m2 i.v. on day 1 of cycle 1 + 2 and 300mg/m2 i.v. on day 1 of cycle 3 + 4 and etoposide (E) 120 mg/m2i.v. on day 1–3 of each cycle. Patients were randomisedto receive P-100 for ten days following chemotherapy duringeither the first or second cycle. 12 Patients received P-100with the first and 12 with the second cycle. For each groupcycles with P-100 were compared to cycles without P-100. Results: P-100 was well tolerated but no significant differencesbetween cycles with and without P-100 were seen in the administeredchemotherapy dose, depth and duration of neutropenia, numberof blood or platelet transfusions, WHO grade 3–4 infectionor requirement for intravenous antibiotics. Of 24 evaluablepatients 14 (58.3%) achieved CR and 4 (16.6%) PR. Patients achievingCR received radiotherapy. The median time to progression was169 days (range 38–995+ days) and the median survivaltime was 305 days (range 42–1052+ days). Three patientsare alive after 2 years (11.5%), 2 without relapse (7.7%). Alopecia,nausea and vomiting occurred in all patients but no treatmentrelated deaths occurred. Conclusion: In this study P-100 did not significantly influencethe myelotoxicity associated with carboplatin-etoposide chemotherapyin the treatment of SCLC. urinary-derived Monocyte-Colony Stimulating Factor, P-100, carboplatin, etoposide, SCLC     

Inhibition of tissue factor/factor VIIa activity in plasma requires factor X and an additional plasma component

A study was carried out to explore requirements for the inhibition of tissue factor-factor VIIa enzymatic activity in plasma. Reaction mixtures contained plasma, 3H-factor IX or 3H-factor X, tissue factor (vol/vol 2.4% to 24%), and calcium. Tissue factor-factor VIIa activity was evaluated from progress curves of activation of factor IX or factor X, plotted from tritiated activation peptide release data. With normal plasma, progress curves exhibited initial limited activation followed by a plateau indicative of loss of tissue factor-factor VIIa activity. With hereditary factor X-deficient plasma treated with factor X antibodies, progress curves revealed full factor IX activation. Adding only 0.4 micrograms/mL factor X (final concentration) could restore inhibition. Inhibition was not observed in purified systems containing 6% to 24% tissue factor, factor VII, 0.5 micrograms/mL, factor IX, 13 micrograms/mL, and factor X up to 0.8 micrograms/mL, but could be induced by adding barium-absorbed plasma to the reaction mixture. Thus, both factor X and an additional material in plasma were required for inhibition. The amount of factor X needed appeared related to the concentration of tissue factor; adding more tissue factor at the plateau of a progress curve induced further activation. These results also indicate that inhibited reaction mixtures contained active free factor VII(a). Preliminary data suggest that inhibition may stem from loss of activity of the tissue factor component of the tissue factor- factor VII(a) complex.     

The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential

The stepwise commitment from hematopoietic stem cells in the bone marrow to T lymphocyte-restricted progenitors in the thymus represents a paradigm for understanding the requirement for distinct extrinsic cues during different stages of lineage restriction from multipotent to lineage-restricted progenitors. However, the commitment stage at which progenitors migrate from the bone marrow to the thymus remains unclear. Here we provide functional and molecular evidence at the single-cell level that the earliest progenitors in the neonatal thymus had combined granulocyte-monocyte, T lymphocyte and B lymphocyte lineage potential but not megakaryocyte-erythroid lineage potential. These potentials were identical to those of candidate thymus-seeding progenitors in the bone marrow, which were closely related at the molecular level. Our findings establish the distinct lineage-restriction stage at which the T cell lineage-commitment process transits from the bone marrow to the remote thymus.     

Does Previous Head and Neck Irradiation Increase the Chance of Multigland Disease in Patients with Hyperparathyroidism?

Background  

Exposure to therapeutic radiation, whether used to treat lymphoma, breast cancer, or benign conditions, such as acne, is thought to cause an increased risk for thyroid and/or parathyroid neoplasia. We therefore investigated whether patients with a history of head/neck irradiation and hyperparathyroidism (HPT) had a higher incidence of multigland disease.