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Biomedical subjects

Jennifer L Rudolph

Publications and source records attributed to Jennifer L Rudolph.

7 recordsLinked to original sources

Analysis of Rit signaling and biological activity.

Rit (Ras-like expressed in many tissues) is the founding member of a novel subgroup within the larger Ras superfamily of small GTP-binding proteins. Although Rit shares more than 50% amino acid identity with Ras, it contains a unique effector domain in common with the closely related Rin and Drosophila Ric proteins and lacks the C-terminal lipidation motifs critical for the membrane association and biological activity of many Ras proteins. Interestingly, whereas Rit has only modest transforming ability when assayed in NIH 3T3 cells, Rit exhibits neuronal differentiation activities comparable to those of oncogenic mutants of Ras when assayed in PC12 and other neuronal cell lines. This cell-type specificity is explained in part by the ability of Rit to selectively activate the neuronal Raf isoform, B-Raf. Importantly, Rit seems to play a critical role in neurotrophin-mediated MAP kinase signaling, because Rit gene silencing significantly alters NGF-dependent MAP kinase signaling and neuronal differentiation. In this chapter, we discuss the reagents and methods used to characterize Rit-mediated signaling to MAP kinase-signaling pathways to determine the extracellular stimuli that regulate Rit activation and to characterize Rit-induced neuronal differentiation.

Animals↗

Activated RIC, a small GTPase, genetically interacts with the Ras pathway and calmodulin during Drosophila development.

The mammalian Rit and Rin proteins, along with the Drosophila homologue RIC, comprise a distinct and evolutionarily conserved subfamily of Ras-related small GTP-binding proteins. Unlike other Ras superfamily members, these proteins lack a signal for prenylation, contain a conserved but distinct effector domain, and, in the case of Rin and RIC, contain calmodulin-binding domains. To address the physiological role of this Ras subfamily in vivo, activated forms of the Drosophila Ric gene were introduced into flies. Expression of activated RIC proteins altered the development of well-characterized adult structures, including wing veins and photoreceptors of the compound eye. The effects of activated RIC could be mitigated by a reduction in dosage of several genes in the Drosophila Ras cascade, including Son of sevenless (Sos), Dsor (MEK), rolled (MAPK), and Ras itself. On the other hand, reduction of calmodulin exacerbated the defects caused by activated RIC, thus providing the first functional evidence for interaction of these molecules. We conclude that the activation of the Ras cascade may be an important in vivo requisite to the transduction of signals through RIC and that the binding of calmodulin to RIC may negatively regulate this small GTPase.

Amino Acid Sequence↗

Emerging melanoma vaccines.

No satisfactory treatment currently exists for melanoma once it has spread beyond its original site. At present, the only FDA-approved treatment for advanced melanoma is IFN-alpha2b. Vaccines are an experimental therapy intended to stimulate the immune system to react more strongly against patients' own melanoma cells, thereby destroying the tumour or slowing its progression. Unfortunately, the exact tumour antigens that can stimulate an effective tumour-protective response in humans remain unknown. The approach that is increasingly followed to circumvent this problem is to prepare polyvalent vaccines containing a variety of melanoma antigens, as the greater the number of antigens in a vaccine, the greater the chance it will contain the correct antigen(s) to stimulate an antitumour response. Two recent randomised trials suggest that this approach results in vaccines that can be clinically effective. One is a double-blind, placebo-controlled trial of a polyvalent, shed antigen melanoma vaccine developed by Bystryn and licenced to NeoVac; the other is a larger randomised trial of Melacine (Corixa Corp.), a vaccine prepared from the lysate of two melanoma cell lines adjuvanted with Detox, which was developed by Mitchell and commercialized by Corixa. In both cases, tumour progression was delayed in the vaccine-treated patients, although in the latter trial, this was only observed in patients with certain human leukocyte antigen phenotypes. Several other vaccines are currently in Phase III trials, but the results of these trials are still pending. The major issues that need to be addressed are designing more effective melanoma vaccines with a mix of melanoma-associated antigens that can stimulate clinically beneficial antitumour immune responses, and finding an adjuvant that can safely, easily and powerfully boost the frequency and magnitude of these responses.

Animals↗

Contraceptive self-efficacy: does it influence adolescents' contraceptive use?

This research investigates the relationship between contraceptive self-efficacy and contraceptive use, measured one year later, among adolescent boys and girls. Data are obtained from the two waves of the restricted use sample of the National Longitudinal Study of Adolescent Health (n = 3,577). Employing multiple regression and logistic regression strategies, we examine whether demographic and background characteristics influence contraceptive self-efficacy, and whether contraceptive self-efficacy increases the likelihood of contraceptive use. We find that adolescents who are female, older, live with step-parents, and whose mothers approve of contraceptive use report higher contraceptive self-efficacy, while adolescents whose mothers did not complete high school report lower contraceptive self-efficacy. Results partially support the expectation that adolescents with higher contraceptive self-efficacy act accordingly by using contraceptives.

Adolescent↗

Pemphigus.

Pemphigus is a rare autoimmune disease that results in blistering of the skin and oral cavity. It is caused by autoantibodies directed against cell-surface antigens on keratinocytes, which when targeted lose their cellular adhesion properties and separate from one another to form blisters within the epidermis. Differences in the particular antigens targeted by the antibodies and in the distribution of these antigens in the different regions of the body and in the separate layers of the epidermis result in different clinical manifestations of the disease. The disease is diagnosed based on its clinical manifestations (flaccid blisters and erosions on skin and oral mucosa), histology (epidermal acantholysis), and immunological abnormalities (circulating and tissue-fixed antibodies against keratinocyte surface antigens). Pemphigus, which if left untreated is almost always fatal, is generally managed with topical, oral, or intralesional corticosteroids. Other options include plasmapheresis and intravenous immunoglobulin (IVIg), coupled with cytotoxic drugs. Immunosupressants, anti-inflammatory drugs, and antibiotics are used as adjuvants, but apart from IVIg, these therapy options are non-specific and more research is needed to develop treatments with improved side-effect profiles.

Humans↗