Numerical techniques and mathematical modelling for CI857-controlled gene expression and cell growth in recombinant E. coli

Author to whom all correspondence should be addressed. E-mail: rcubarsi{at}mat.upc.es Recombinant gene expression, monitored by ß-galactosidaseactivity, is studied in a PL, PR-C1857 plasmid expression systemin temperature-induced E. coli batch cultures. The experimentalprocedure has been mathematically modelled, and the correspondingparameters are estimated from specific statistical and numericalmethods, basically by using a global least-squares procedureunder some constraints induced by the model. The numerical techniquesproposed in this work act by accumulation of data coming fromseveral runs of the modelled experiment, so that more accuracyis obtained in the parameter estimation. In particular, forthe production process, an extra-model parameter depending onan indicator vector is introduced for each run of the experimentin order to globalize the data. The analysis of the data obtainedleads to an integrated model for both cell growth and gene expression,which describes an asymmetric dynamics between culture growthand recombinant protein yield, and can serve to predict themaximal value of accumulated gene expression and the time requiredfor it to be achieved at any age of the preinducing cell growth.     

Up-Regulated Expression of CD56+, CD56+/ CD16+, and CD19+ Cells in Peripheral Blood Lymphocytes in Pregnant Women With Recurrent Pregnancy Losses

PROBLEM : To analyze immunophenotypic profiles of peripheral blood and humoral autoimmune responses in women with a history of recurrent spontaneous abortions (RSA). METHOD : Peripheral blood lymphocyte subsets by flow cytometry and autoantibodies to phospholipids and nuclear components by ELISA were measured in non pregnant and pregnant women with RSA of unknown etiology. Thirty-five pregnant and eighty-one nonpregnant women with RSA were studied. Seventeen nonpregnant and twenty-two pregnant normal controls were included. RESULTS : Natural killer (NK) cells (CD56+) were significantly elevated in nonpregnant women with RSA as compared with nonpregnant controls. Pregnant women with RSA demonstrated significantly increased NK (CD56+, CD56+/CD16+) and B cells (CD19+) as compared with pregnant controls. Women who miscarried the index pregnancy demonstrated significantly lower CD3+ cells in comparison with normal controls. Women with RSA and antiphospholipid antibodies showed significantly elevated NK cells when compared with women without antiphospholipid antibodies. Women with autoantibodies to nuclear components demonstrated significantly elevated CD19+/CD5+ cells when compared to women without autoantibodies to nuclear components. CONCLUSIONS : Women with RSA demonstrate an abnormal cellular immune response by increasing peripheral natural killer cells and B cells as compared with normal controls.     

Calcium Hydroxylapatite versus Nonanimal Stabilized Hyaluronic Acid for the Correction of Nasolabial Folds: A 12-Month, Multicenter, Prospective, Randomized, Controlled, Split-Face Trial

BACKGROUND Fillers continue to proliferate in dermatology. Rigorous clinical trials can help determine the advantages and disadvantages of these products as they come to market.
OBJECTIVE This randomized, split-face, controlled study compared the efficacy, safety, durability, and volumes of calcium hydroxylapatite (CaHA) versus nonanimal-stabilized hyaluronic acid (NASHA) in nasolabial folds.
METHODS AND MATERIALS Sixty patients were enrolled at two medical clinics in Europe (Summer 2005). Patients received two injections 3 months apart. Patients returned at 6, 9, and 12 months for a blinded evaluation, using accepted aesthetic rating scales. Adverse events were recorded throughout the study.
RESULTS At all time points, CaHA was found to be more effective than NASHA. At 12 months, 79% of CaHA folds were still improved or better versus 43% of NASHA folds ( p <.0001). In addition, 30% less total CaHA volume was required compared to NASHA. Evaluators assessed CaHA as superior in 47% of patients and inferior in only 5% ( p <.0001). Blinded evaluators and patients preferred CaHA two to one ( p <.05). Both products were safe and well tolerated.
CONCLUSION CaHA was found to be significantly more effective than NASHA. At all time points, CaHA demonstrated longer lasting results and greater improvement than NASHA.     

Humoral Factor(s) in Experimental Hypersplenism

A type of experimental hypersplenism characterized by splenomegaly andthrombocytopenia has been produced in the rat by the repeated intraperitoneal injection of methylcellulose. The urine of these animals was collectedand given through a gastric tube to another group of normal rats for a periodof 4 weeks. The results were a marked and rapidly developing thrombocytopenia, a delayed but definite anemia with mild reticulocytosis and leukocytosis. When the administration of urine was discontinued, the anemia regressed,but the thrombocytopenia persisted unmodified for 2 weeks. When the urineof hypersplenic rats was again given to this group for 6 additional weeks, itfailed to induce anemia or to change the persistent thrombocytopenia. Intragastric administration of urine from normal rats, from rats made anemic bytotal body radiation and from the hypersplenic group after splenectomy toother groups of normal rats, failed to produce the same changes and onlyinduced moderate leukocytosis.

On the basis of these results, it is postulated that in experimental methylcellulose-hypersplenism in the rat there is a humoral factor(s) responsiblefor the thrombocytopenia, that this humoral factor(s) is eliminated in theurine and that when such urine is given to normal rats, it is responsible forthe thrombocytopenia and partially for the anemia that are observed. Suchfactor(s) are in some important way related to the presence of the spleen.

Submitted on October 16, 1959 Accepted on March 8, 1960