Preparation of an engineered safer immunotoxin against colon carcinoma based on the ribotoxin hirsutellin A

Immunotoxins are chimeric proteins composed of an antibody domain that specifically directs the action of the toxic domain, resulting in the death of the targeted cells. Over recent years, immunotoxins have been widely studied and the number of different constructions has increased exponentially. Protein engineering has allowed the design of optimized versions of immunotoxins with an improved tumor binding affinity, stability or cytotoxic efficacy, although sometimes this has compromised the safety of the patient in terms of undesirable adverse secondary reactions. A triple mutant at three Trp residues (HtA3DW) of the ribotoxin hirsutellin A retains its specific ribonucleolytic activity, although cell internalization capacity is lacking.This toxin variant has been fused to the single chain variable fragment A33 (scFvA33). This immunoconjugate (IMTXA33HtA3DW) was produced in the methylotrophic yeast Pichia pastoris and purified using nickelnitrilotriacetic acid affinity chromatography. Both target and toxic domains were characterized. The immunotoxin showed an exquisite specific binding against GPA33-positive culture cells, which results in the death of the targeted cells because of specific ribonucleolytic activity against ribosomes of the engineered hirsutellin A variant. IMTXA33HtA3DW represents a promising structure in the search for an improved immunotoxin without compromising the safety of patients.

A randomized trial of nebulized 3% hypertonic saline with salbutamol in the treatment of acute bronchiolitis in hospitalized infants

OBJECTIVE: Acute bronchiolitis is a common disorder of infants that often results in hospitalization. Apart from supportive care, no therapy has been shown to influence the course of the disease, except for a possible effect of nebulized hypertonic saline (HS). To determine whether this does have beneficial effects on length of stay in hospital or on severity scores, we undertook a double-blind, randomized, controlled trial in a pediatric department of a Portuguese hospital. METHODS: Previously healthy infants, younger than 12 months, hospitalized with mild-to-moderate acute viral bronchiolitis were randomized to receive either nebulized 3% (hypertonic, HS) or 0.9% (normal, NS) saline during their entire hospital stay. Primary endpoints were: length of hospital stay and severity scores on each day of hospitalization. Need for supplemental oxygen, further add-on medications and adverse effects were also analyzed. RESULTS: Sixty-eight patients completed the study (HS: 33; NS: 35). The median length of hospital stay did not differ between groups: HS: 5.6 ± 2.3 days; NS: 5.4 ± 2.1 days (P = 0.747). We found no difference between groups in severity scores from day 1 to day 4. There were no differences in need for supplemental oxygen or add-on medications. Patients in HS group had significantly more cough (46% vs. 20%, P = 0.025) and rhinorrhoe (58% vs. 31%, P = 0.30). CONCLUSION: This study does not support the use of nebulized HS over NS in therapy of hospitalized children with mild-to-moderate acute viral bronchiolitis

Saline Township (Mich.) residences and business, ca. 1874

Left to right: Res. of Orange Risdon, Sec. 1, Saline Tp. Mich.; Res. of Andrew Bush, Sec. 3, Saline Tp. Mich.; Res. of Dudley Miller, Sec. 24, Saline Tp. Mich.; Saline Exchange, A. Harmon Prop, Saline, Mich.; Res. of Abram Davenport, Sec. 36, Saline Tp. Mich.; Res. of Milton Reynolds, Sec. 22, Saline Tp. Mich.; Res. of George Neissle, Sec. 12, Saline Tp. Mich.; Res. of Robert Hammond, Sec. 25, Saline Tp. Mich.; Res. of M. Himerdinger, Sec. 8, Saline Tp. Mich. Publication information: Chicago, Ill. : Everts & Stewart, 1874.

Map of Saline Township. T.P. No. 4 S. Range No. 5 E [plat]

Publication information: Chicago, Ill. : Everts & Stewart, 1874.

Saline Township (Mich.) residences, ca. 1874

Left to right: Res. of Robert Shaw, Sec. 24, Saline Tp. Mich.; Res. of Aaron L. Feldkamp, Sec. 7, Saline Tp. Mich.; Farm residence of A.K. Clark, Sec. 14, Saline Tp. Mich.; Res. of A.K. Clark, Sec. 1, Saline Village, Mich.; Res. of Harvey Bennett, Sec. 1, Saline Tp. Mich.; Res. of George Osborn, Sec. 35, Saline Tp. Mich. Publication information: Chicago, Ill. : Everts & Stewart, 1874.

Saline & York Township (Mich.) residences and business, ca. 1874

Left to right: Res. of Henry A. Hammond, Sec. 26, Saline Tp. Mich.; Res. of Lewis Andrews, architect & builder, Saline, Mich.; Res. of E.C. Robinson, Saline Tp. Mich.; Res. of J.U. Fuller, Sec. 26 York Tp. Mich.; Res. of Daniel Aylsworth, Sec. 26, York Tp. Mich.; Res. of Wm. Dexter, Sec 26, York Tp. Mich.; Res. of Thos. H. Fuller, Sec. 24, York Tp. Mich. Publication information: Chicago, Ill. : Everts & Stewart, 1874.

York, Saline, Ypsilanti, Lyndon, Sharon (Mich.) Township residences, ca. 1874

Left to right: Res. of C. Parsons, Saline, Mich.; Res. of D.B. Green, Ypsilanti, Mich.; Res. of Justus Corwin, Sec. 17, York Tp. Mich.; Res. of Robert Howlett, Sec. 20, Lyndon Tp. Mich.; Res. of Wm. Basom, Sec. 2, York Tp. Mich.; Res. of Jay Everett, Sec. 2, sharon Tp. Mich. Publication information: Chicago, Ill. : Everts & Stewart, 1874.

Lyndon, Saline and Ann Arbor (Mich.) residences and business, ca. 1874

Left to right: Woodside Res. of N.B. Cole, Ann Arbor, Mich. for sale; Res. of John K. Yocum, Sec. 30, Lyndon Tp. Mich; Corner Main & Liberty Sts., Ann Arbor, Mich.; C. Parsons, dealer in dry goods, boots & shoes, hats, caps &c., Saline Mich. Publication information: Chicago, Ill. : Everts & Stewart, 1874.

Saline [plat]

Scale 6 chains per inch. Drawn and compiled by Frank Krause, C.E., Ann Arbor, Mich.Publication information: Chicago, Ill. : Everts & Stewart, 1874.

Saline County soils /

Cover title.