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Biomedical subjects

A Pavlovsky

Publications and source records attributed to A Pavlovsky.

At least 19 recordsLinked to original sources

Crystal structure of human recombinant interleukin-4 at 2.25 A resolution.

The crystal structure of human recombinant interleukin-4 (IL-4) has been solved by multiple isomorphous replacement, and refined to an R factor of 0.218 at 2.25 A resolution. The molecule is a left-handed four-helix bundle with a short stretch of beta sheet. The structure bears close resemblance to other cytokines such as granulocyte-macrophage colony stimulating factor (GM-CSF). Although no sequence similarity of IL-4 to GM-CSF and other related cytokines has been previously postulated, structure-based alignment of IL-4 and GM-CSF revealed that the core of the molecules, including large parts of all four helices and extending over half of the molecule, has 30% sequence identity. This may have identified regions which are not only important to maintain structure, but could also play a role in receptor binding.

Amino Acid Sequence

Rosette forming T-cells in human lymphomas: relationship with age and clinical parameters.

Peripheral blood spontaneous rosette forming T cells (RFC) were studied in 40 Hodgkin's Disease (HD) and 20 lymphosarcoma (LS) patients, classified according to the histological type and spread of disease and to their age, treatment, clinical condition and evolution. LS patients had near normal RFC values; in HD, the lowest values of RFC corresponded to the most severe histological picture. In all patients, differences could be seen according to the spread of the disease and the clinical condition, but none in relation with treatment nor with the clinical evolution in a one year period after the test. While in controls and LS patients, RFC were higher in younger than older subjects, in HD, values were higher after 50 years of age. The usefulness of RFC test in the evaluation of lymphoma patients is discussed.

Adolescent

Physical, chemical and immunological studies on bovine factor VIII.

Highly purified bovine factor VII prepared according to our technique and having a specific activity of 500 U/mg protein has been studied. The chemical analysis of the preparation revealed it to be composed of amino acids, lipids (8-10%) and carbohydrates (7%). The lipid moiety can be removed by chromatography. Different mechanism of inactivation of bovine factor VII and the possible molecular changes induced by the inactivating agents were studied. EDTA and EGTA provoke a weakening of the bonds linking the structural elements of the molecule, which allows for the separation of two different components of the molecule by gel filtration. Upon treatment with thrombin, the carbohydrate content of bovine factor VIII decreases without any apparent degradation of the protein moiety of the molecule. The fact that precipitating and neutralizing antisera against factor VIII were obtained, shows that the molecules modified by EDTA and thrombin still have the antigenic properties of factor VIII. The inhibitor developed by hemophiliacs transfused with human factor VIII is bound to bovine factor VIII, forming a complex reveal that it is composed of bovine factor VIII and human gamma-globulin. Bovine factor VIII in the complex retains some antigenic determinants which bind rabbit antiserum against bovine factor VIII, as shown by neutralization of the antiserum and by precipitation studies.

Animals

Sequential therapy for induction and maintenance of remission in acute myeloblastic leukemia.

A total of 114 previously untreated patients with myeloblastic leukemia was included in a sequential therapy protocol. Daunorubicin, vincristine, and prednisone were employed for the first 3 weeks, followed by two or more 5-day courses of cytosine arabinoside and 6-mercaptopurine; there was a 5-day rest between courses. Maintenance therapy was as follows: the continuing 6-mercaptopurine and methotrexate treatment was interrupted every 30 days for sequential reinforcement courses consisting of one dose of daunorubicin and vincristine and 7 days of prednisone, or by a 5-day course of cytosine arabinoside plus 6-mercaptopurine. Of the 114 patients, 48 obtained complete remission, 14 had partial remission, 16 failed to respond, and 36 died during the course of treatment. The remission rate in children (under 16) was 57%; in adults (16-45) 54%; and in those over 45, 19%. The difference in the incidence of complete remission in patients under 45 and those over 45 was statistically significant (p less than 0.01). The median duration of complete remission was 8 months: 12 months in children and 5 months in adults. The over-all survival rate was 4 months: 13 months for patients with complete remission, 4 months for those with partial remission, and 1 month for patients who did not respond to therapy. The difference in survival of those with complete remission and all the others was significant (p less than 0.01).

Adolescent

Combined cyclophosphamide vincristine, procarbazine, and prednisone (COPP) therapy of malignant lymphoma. Evaluation of 190 patients.

One hundred ninety patients who had advanced active Hodgkin's disease, lymphosarcoma, or reticulum cell sarcoma were treated with a combination of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) given in a cyclical fashion every month. Complete remission was produced in 91 of 138 (66%) patients with Hodgkin's disease and in 39 of 52 (75%) patients with non-Hodgkin's lymphoma (lymphosarcoma and reticulum cell sarcoma). The response rate was higher in patients who completed six cycles of therapy compared to those who completed only three to five cycles: 77% vs. 45%, respectively, in Hodgkin's disease, and 85% vs. 46%, respectively, in non-Hodgkin's lymphoma. The median duration of remission was longer for Hodgkin's disease patients who completed six cycles (30 months vs. 10 months). The median duration of complete remission of non-Hodgkin's lymphoma was 14 months. The response to treatment correlated positively with survival. The median survival time start of COPP treatment for patients with Hodgkin's disease was 7 months for nonresponders, 14 months for those who attained partial remission, and more than 48 months for those who attained complete remission. For patients with non-Hodgkin's lymphoma, the median survival time from start of COPP treatment was 24 months for nonresponders and those who had partial remission, and more than 32 months for those who attained complete remission. Of complete remission responders with Hodgkin's disease, 70% are still alive 84 months after diagnosis, and 63% of the patients witn non-Hodgkin's lymphoma are still alive 48 months after diagnosis.

Adolescent