[Obra selecta. Francés]

Sign.:*11, A-R12, S4

[Obra selecta. Frances]

Fe de erratas

A physiologic function for p-glycoprotein (MDR-1) during the migration of dendritic cells from skin via afferent lymphatic vessels

P-glycoprotein (MDR-1) is a well-known transporter that mediates efflux of chemotherapeutic agents from the intracellular milieu and thereby contributes to drug resistance. MDR-1 also is expressed by nonmalignant cells, including leukocytes, but physiologic functions for MDR-1 are poorly defined. Using an initial screening assay that included >100 mAbs, we observed that neutralizing mAbs MRK16, UIC2, and 4E3 against MDR-1 specifically and potently blocked basal-to-apical transendothelial migration of mononuclear phagocytes, a process that may mimic their migration into lymphatic vessels. Antagonists of MDR-1 then were used in a model of authentic lymphatic clearance. In this model, antigen-presenting dendritic cells (DC) migrate out of explants of cultured human skin and into the culture medium via dermal lymphatic vessels. DC and T cells derived from skin expressed MDR-1 on their surfaces. Addition of anti-MDR-1 mAbs MRK16, UIC2, or the MDR-1 antagonist verapamil to skin explants at the onset of culture inhibited the appearance of DC, and accompanying T cells, in the culture medium by approximately 70%. Isotype-matched control mAbs against other DC molecules including CD18, CD31, and major histocompatibility complex I did not block. In the presence of MDR-1 antagonists, epidermal DC were retained in the epidermis, in contrast to control conditions. In summary, this work identifies a physiologic function for MDR-1 during the mobilization of DC and begins to elucidate how these critical antigen-presenting cells migrate from the periphery to lymph nodes to initiate T lymphocyte-mediated immunity.

Coexpression of NF-kappa B/Rel and Sp1 transcription factors in human immunodeficiency virus 1-induced, dendritic cell-T-cell syncytia.

Productive infection of T cells with human immunodeficiency virus 1 (HIV-1) typically requires that the T cells be stimulated with antigens or mitogens. This requirement has been attributed to the activation of the transcription factor NF-kappa B, which synergizes with the constitutive transcription factor Sp1 to drive the HIV-1 promoter. Recently, we have found that vigorous replication of HIV-1 takes place in nonactivated memory T cells after syncytium formation with dendritic cells (DCs). These syncytia lack activated cells as determined by an absence of staining for Ki-67 cell cycle antigen. The expression and activity of NF-kappa B and Sp1 were, therefore, analyzed in isolated T cells and DCs from humans and mice. We have used immunolabeling, Western blot analysis, and electrophoretic mobility shift and supershift assays. T cells lack active NF-kappa B but express Sp1 as expected. DCs express high levels of all known NF-kappa B and Rel proteins, with activity residing primarily within RelB, p50, and p65. However, DCs lack Sp1, which may explain the failure of HIV-1 to replicate in purified DCs. Coexpression of NF-kappa B and Sp1 occurs in the heterologous DC-T-cell syncytia that are induced by HIV-1. Therefore, HIV-1-induced cell fusion brings together factors that upregulate virus transcription. Since DCs and memory T cells frequently traffic together in situ, these unusual heterologous syncytia could develop in infected individuals and lead to chronic HIV-1 replication without ostensible immune stimulation.

II. Academic notebook, [ca. 1745]

This paper notebook contains undated and unattributed handwritten summaries and notes from published texts on world history, religion, and natural history, and was presumably kept by William Sever. The first page notes the death of poet Alexander Pope in 1744, constituting the latest date referenced in the notebook. The entries are typically short and offer condensed information on subjects including the histories of England, Japan and Siam; early Christian history; and natural religion.

Commonplace book of Jonathan Belcher, 1725-1727

This leather-bound volume contains excerpts copied by Jonathan Belcher from books he read while he was a student at Harvard. The excerpts come from a variety of sources including periodicals and contemporary publications. The inside cover has Belcher's bookplate with the motto, "Sustine. Abstine." The back cover has some additional personal information including reference to French lessons with "Mr Law Merciers," and notes of the dates when he began certain books/essays.

Letters from Charles Loring to William Tudor,

Three letters regarding the legal dispute between John Dorr and the Peruvian government over the condemnation of Dorr’s ship, Esther. Loring was the attorney for the defendant, Paschal Pope. Tudor was authorized to depose witnesses in his capacity as United States consul.

John Dorr legal documents,

Legal document from Commonwealth of Massachusetts relating to the case between John Dorr and Paschal P. Pope; it empowers Tudor to take the depositions of Eliphalet Smith and Henry D. Tracy, and includes questions by the attorneys for each, Charles Loring (Pope, defendant) and Bradford Summers (Dorr, plaintiff).

Letter from James Winthrop to William Bentley, 1784 May 17

Two octavo-sized leaves containing a two-and-a-half-page handwritten letter from Winthrop to Bentley discussing Alexander Pope and mythology, and a brief criticism of John Moore's A view of society and manners.