Nucleotide-dependent behavior of single molecules of cytoplasmic dynein on microtubules in vitro.

We visualized the nucleotide-dependent behavior of single molecules of mammalian native cytoplasmic dynein using fragments of dynactin p150 with or without its N-terminal microtubule binding domain. The results indicate that the binding affinity of dynein for microtubules is high in AMP-PNP, middle in ADP or no nucleotide, and low in ADP.Pi conditions.

Impact of highly conserved HLA haplotype on acute graft-versus-host disease.

Although the effects of human leukocyte antigen (HLA) locus matching on clinical outcome in unrelated hematopoietic stem cell transplantations have been characterized, the biologic implications of HLA haplotypes have not been defined. We demonstrated the genetic fixity of Japanese conserved extended haplotypes by multi-single nucleotide polymorphism analysis in 1810 Japanese donor-recipient pairs matching with HLA-A, -B, -C, -DRB1, and -DQB1 alleles. Three major Japanese conserved extended haplotypes (named HP-P1, HP-P2, and HP-P3) were essentially completely conserved at least in the 3.

Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens.

The adoptive transfer of donor T cells that recognize recipient minor histocompatibility antigens (mHAgs) is a potential strategy for preventing or treating leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). A total of 7 patients with recurrent leukemia after major histocompatibility complex (MHC)-matched allogeneic HCT were treated with infusions of donor-derived, ex vivo-expanded CD8(+) cytotoxic T lymphocyte (CTL) clones specific for tissue-restricted recipient mHAgs. The safety of T-cell therapy, in vivo persistence of transferred CTLs, and disease response were assessed.

Transient inhibition of NF-kappaB by DHMEQ induces cell death of primary effusion lymphoma without HHV-8 reactivation.

Primary effusion lymphoma (PEL) is a refractory malignancy caused by human herpes virus 8 (HHV-8) in immunocompromised individuals. The tumor cells of PEL are characterized by constitutive NF-kappaB activation. Dehydroxymethylepoxyquinomicin (DHMEQ) is a new NF-kappaB inhibitor and is effective on various tumor cells with constitutively activated NF-kappaB.

Anti-allergic drug olopatadine suppresses murine contact hypersensitivity and downmodulates antigen-presenting ability of epidermal Langerhans cells.

Olopatadine hydrochloride is an H1-receptor-blocker but has other anti-allergic pharmacological potencies. We investigated whether olopatadine inhibits murine contact hypersensitivity, focussing on its modulatory action on epidermal Langerhans cells serving as antigen-presenting cells. While BALB/c mice were sensitized and challenged epicutaneously with hapten, they were administered intraperitoneally with olopatadine.