作者: Wittich, Christoph ; Lang, Alexander ; Padrini, Giacomo ; Floss, Doreen M ; Ettich, Julia ; Cruz, Patricia Rodrigues ; Moll, Jens M ; Köhrer, Karl ; Petzsch, Patrick ; Seibel, Christiane ; Scheller, Jürgen ; Rafii, Puyan

Ciliary neurotrophic factor (CNTF) activates cells via the non-signaling α-receptor CNTF receptor (CNTFR) and the two signaling β-receptors glycoprotein 130 (gp130) and leukemia inhibitory factor receptor (LIFR). The CNTF derivate, Axokine, was protective against obesity and insulin resistance, but clinical development was halted by the emergence of CNTF antibodies. The chimeric cytokine IC7 used the framework of interleukin (IL-)6 with the LIFR-binding site from CNTF to activate cells via IL-6R:gp130:LIFR complexes. Similar to CNTF/Axokine, IC7 protected mice from obesity and insulin resistance. Here, we developed CNTF-independent chimeras that specifically target the IL-6R:gp130:LIFR complex. In GIL-6 and GIO-6, we transferred the LIFR binding site from LIF or OSM to IL-6, respectively. While GIO-6 signals via gp130:IL-6R:LIFR and gp130:IL-6R:OSMR complexes, GIL-6 selectively activates the IL-6R:gp130:LIFR receptor complex. By re-evaluation of IC7 and CNTF, we discovered the Oncostatin M receptor (OSMR) as an alternative non-canonical high-affinity receptor leading to IL-6R:OSMR:gp130 and CNTFR:OSMR:gp130 receptor complexes, respectively. The discovery of OSMR as an alternative high-affinity receptor for IC7 and CNTF designates GIL-6 as the first truly selective IL-6R:gp130:LIFR cytokine, whereas GIO-6 is a CNTF-free alternative for IC7.

2020-04-01·The Journal of Hand Surgery3区 · 医学

Transfers of the Ipsilateral C7 Plus the Spinal Accessory Nerve Versus Triple Nerve Transfers for Treatment of C5-C6 Avulsion of the Brachial Plexus

3区 · 医学

Article

作者: Song, Jie ; Gu, Yu-Dong ; Qiu, Wen-Jun ; Hu, Shao-Nan ; Wu, Ji-Xin ; Chen, Liang

PURPOSETo compare the long-term results of transfers of the ipsilateral C7 (IC7) plus spinal accessory nerve (SAN) with those of triple nerve transfers (TNT) using one fascicle of the ulnar nerve to the biceps motor branch (Oberlin's procedure), SAN transferred to the suprascapular nerve, and transfer of the long head of triceps nerve branch to the anterior branch of axillary nerve to treat C5-C6 avulsion of the brachial plexus.METHODSThe IC7 group included 9 patients undergoing transfers of IC7 to the upper trunk and SAN to the suprascapular nerve. Median age at surgery was 26 years and interval between injury and surgery was 2.8 months. Patients were observed for a median of 118 months. The TNT group contained 13 patients, median age 33 years; interval between injury and surgery was 3.1 months. Patients were observed for a median of 103 months.RESULTSIn the IC7 group, median shoulder abduction was 105° and median external rotation of the shoulder was 64°, which was similar to that of the TNT group (89° abduction and 58° external rotation). Eight of nine patients recovered at least M3 (Modified Narakas scale) strength of deltoid in the IC7 group, which was similar to that in the TNT group (11 of 13 patients). Six of nine patients achieved at least Medical Research Council grade 3 (MRC3) strength of biceps in the IC7 group, which was similar to that in the TNT group (11 of 13 patients). Of 4 patients in the IC7 group with a preoperative latissimus dorsi strength of MRC3 or less, 3 gained a deltoid strength of M3 or less, and 3 a biceps strength of MRC2 or less.CONCLUSIONSTransfers of IC7 plus SAN provide results comparable to those of TNT for treatment of C5-C6 avulsion.TYPE OF STUDY/LEVEL OF EVIDENCETherapeutic IV.

2008-04-01·Hybridoma

Application of Monoclonal Antibodies in a Rapid Sandwich Dot-Enzyme Linked Immunosorbent Assay for Identification and Antigen Detection ofLeptospiraSerovars

Article

作者: Khushiramani, Rekha ; Shukla, Jyoti ; Sharma, Rashmi ; Batra, H.V. ; Tuteja, Urmil

Monoclonal antibodies (MAbs) were produced by fusing SP2/0 myeloma cells with spleen cells of BALB/c mice that were immunized with live whole cells of the four most prevalent Leptospira serovars--namely, autumnalis, australis, grippotyphosa, and icterohaemorrhagiae. A total of 26 MAbs (10 autumnalis, 5 australis, 4 grippotyphosa, and 7 icterohaemorrhagiae) were produced that showed specific, restricted, or broad cross-reactivity when tested with 19 standard pathogenic and 3 standard saprophytic serovars by MAT and dot-ELISA. Monoclonal antibodies like AT4 and AT5 against serovar autumnalis; AS1 and AS2 against serovar australis; GR1, GR3, and GR4 raised against serovar grippotyphosa; and also the MAbs IC3 to IC7 against serovar icterohaemorrhagiae were all usable as typing reagents in a rapid dot-ELISA. Selected MAbs were subsequently utilized in a rapid sandwich dot-ELISA for identification of Leptospira serovars as well as for antigen detection in experimentally infected mice and guinea pigs. Results of rapid sandwich dot-ELISA were compared with dark field microscopy, culture, and PCR in experimentally infected animals and sandwich dot-ELISA detected the presence of Leptospira antigen during the bacteremia stage in all experimental animals. Besides detecting antigens in animals infected with homologous serovars, the sandwich dot-ELISA employing pooled capture and revealing antibodies also detected Leptospira in the group of animals infected separately with the serovars australis and icterohaemorrhagiae. Results showed PCR to be a reliable and rapid test for demonstration of Leptospira in the plasma samples. The rapid sandwich dot-ELISA appeared more advantageous over PCR in being simple, rapid, field based, and economical. This method shows better promise of being used as a bedside test for routine diagnostic purposes.

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适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床前	德国	University of Kiel	-
2型糖尿病	临床前	澳大利亚	Baker Heart & Diabetes Institute	-
非酒精性脂肪性肝炎	临床前	澳大利亚	Kinomedica Pty Ltd.	-
肥胖	临床前	澳大利亚	Baker Heart & Diabetes Institute	-
肥胖	临床前	德国	University of Kiel	-