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Biomedical subjects

A Kogan

Publications and source records attributed to A Kogan.

At least 19 recordsLinked to original sources

Immunological study of complex formation between soluble transferrin receptor and transferrin.

Transferrin receptor (TfR) is a dimeric transmembrane protein that provides iron transport from plasma to cells by binding and internalization of iron-loaded transferrin (Tf). Soluble transferrin receptor (sTfR) is an extracellular part of the TfR molecule that is truncated from the cell surface and released into the blood stream. Using monoclonal antibodies (HyTest Ltd., Turku, Finland), immunofluorescent methods for sTfR and sTfR-Tf complex determination were developed. Soluble TfR was isolated from human plasma, and complex formation between sTfR and Tf was studied by stepwise complex construction and by FPLC gel filtration. It was found that sTfR could bind two Tf molecules step by step when the sTfR-Tf complex is constructed in the plate wells. FPLC gel filtration of sTfR-Tf mixtures and analysis of sTfR and sTfR-Tf immunological activities in collected fractions showed that sTfR can form different complexes with TF depending upon the ratios between them: a 291-kDa compound is assumed to be a 2:1 sTfR/Tf complex, and a 345-kDa compound is assumed to be a 2:2 sTfR/Tf complex. Isolated sTfR eluted as a 237-kDa protein. FPLC gel filtration of serum revealed that all sTfR in serum is bound to Tf in a 2:2 complex, and no isolated sTfR can be found in serum. This raises the question as to the nature of the bonds that hold two molecules of sTfR together to form a dimer.

Antibodies, Monoclonal↗

Measurements of Kondo and spin splitting in single-electron transistors.

We measure the spin splitting in a magnetic field B of localized states in single-electron transistors using a new method, inelastic spin-flip cotunneling. Because it involves only internal excitations, this technique gives the most precise value of the Zeeman energy Delta=/g/mu(B)B. In the same devices we also measure the splitting with B of the Kondo peak in differential conductance. The Kondo splitting appears only above a threshold field as predicted by theory. However, the magnitude of the Kondo splitting at high fields exceeds 2/g/mu(B)B in disagreement with theory.

Journal Article↗

Recombinant factor VIIa use in cardiac surgery--expanding the arsenal therapy for intractable bleeding?

A 72-year-old patient was admitted for mitral valve replacement because of infective endocarditis. Severe intractable bleeding in the early postoperative period was successfully treated with recombinant activated factor VII (rFVIIa). Thereafter, recovery was uneventful, and the patient was discharged on postoperative day 16. The current clinical aspects and experience of rFVIIa use in cardiac surgery are discussed.

Aged↗

Common mutations in the familial Mediterranean fever gene associate with rapid progression to disability in non-Ashkenazi Jewish multiple sclerosis patients.

Ancient founder mutations in the Mediterranean fever gene, MEFV, are associated with familial Mediterranean fever, a recessive, episodic, inflammatory disease. Since these mutations are reported to express with above normal levels of acute phase reactants in healthy heterozygotes we postulated that the heterozygous phenotype could aggravate the clinical expression of ongoing autoimmune diseases. This study evaluated progression to disability in relapsing-remitting multiple sclerosis (RR-MS) patients of non-Ashkenazi and Ashkenazi origin carrying an MEFV mutation, particularly the detrimental M694V, using the expanded disability status scale (EDSS). In the non-Ashkenazi patients group (n=48), carriers (n=17) presented with a two-fold higher fraction which reached EDSS=3.0 and 6.0 compared to noncarriers (n=31) despite a comparable mean of MS duration. The median time to reach EDSS=3.0 was 2 years in the carriers vs 10 years in noncarriers (P=0.007); The median time to reach EDSS=6.0 was 6 years vs 23 years, respectively (P=0.003). M694V heterozygous patients reached both EDSS milestones earlier than other patients. Progression to disability was not enhanced in Ashkenazi RR-MS carriers (n=12, noncarriers n=59). In conclusion, non-Asheknazi MS patients carrying one mutated MEFV gene, particularly M694V, expressed rapid progression to disability. The expressed mutation may increase inflammatory damage inflicted by autoimmune responses.

Adult↗

Gene therapy to target dendritic cells from blood to lymph nodes.

Peripheral lymph nodes (PLN) are strategic microenvironments where antigen-presenting dendritic cells (DC), loaded with environmental antigens, and naive lymphocytes meet to initiate immune responses. The unique capacity of DC to induce primary immune responses has led to their use in clinical medicine; however, delivering DC to lymph nodes is problematic. Intravenously injected DC cannot access to PLN, while DC injected into tissue migrate inefficiently through lymphatics to PLN. We achieved DC targeting to T-cell areas of PLN by endowing DC with a novel receptor for peripheral node addressin (PNAd), an adhesion molecule present on the lymph node venular endothelium. This novel receptor is a chimeric E/L-selectin (ELS) that, we have previously shown, binds to PNAd. DC were genetically modified by retroviral transduction to express ELS. ELS expression was targeted to tips of microvilli, and mediated rolling of DC on PNAd both in vivo and in vitro. Such genetically engineered DC could extravasate directly from blood through the lymph node endothelium as opposed to nontransduced DC. This study provides evidence that the trafficking of DC can be modified using gene transfer technologies. More efficient delivery of DC to PLN should assist the development of improved vaccination strategies.

Adoptive Transfer↗