Lack of factor VIII detection in humans and dogs with an intron 22 inversion challenges hypothesis regarding inhibitor risk.

Background: Almost half of severe hemophilia A (HA) cases are caused by an intron 22 inversion (Int22Inv) mutation, which truncates the 26-exon F8 messenger RNA (mRNA) after exon 22. Another F8 transcript, F8, is initiated from within F8-intron-22. F8 mRNA consists of a short exon spliced to exons 23 to 26 and is expressed in multiple human cell types.

Coexistent chronic lymphocytic leukemia and squamous cell carcinoma of the larynx.

Chronic lymphocytic leukemia (CLL) is the most common lymphoid malignancy among adults in the Western world. Small lymphocytic lymphoma (SLL) represents the lymphomatous presentation of CLL. We describe a case in which a diagnosis of laryngeal CLL/SLL was made in an 82-year-old man who had undergone laryngectomy and neck dissection for the treatment of squamous cell carcinoma of the larynx.

An in vitro model of hematopoietic stem cell homing demonstrates rapid homing and maintenance of engraftable stem cells.

Hematopoietic stem cell (HSC) homing is believed to rely heavily on adhesion interactions between stem cells and stroma. An in vitro assay was developed for adhesion of engraftable HSCs in bone marrow suspensions to pre-established Dexter-type long-term bone marrow culture stromal layers. The cell numbers in the adherent layer and supernatant were examined, along with the engraftment capability of adherent layer cells to indicate the number of HSCs that homed to in vitro stroma.

Characterization of engraftable hematopoietic stem cells in murine long-term bone marrow cultures.

Objective: Long-term bone marrow cultures (LTBMC) are a potential source of hematopoietic stem cells (HSC) for transplantation. Previous reports indicate that feeding LTBMCs induces hematopoietic progenitor cycling, and other studies link HSC cycle phase with engraftability. Our study was initiated to further characterize LTBMC engraftability and determine if a cycle phase-related engraftment defect affects HSC from LTBMCs.

Release of sulfur mustard-modified DNA bases by Escherichia coli 3-methyladenine DNA glycosylase II.

The toxic effects of sulfur mustard have been attributed to DNA modification with the formation of 7-hydroxyethylthioethyl guanine, 3-hydroxyethylthioethyl adenine and the cross-link, di-(2-guanin-7-yl-ethyl)sulfide. To investigate the action of bacterial 3-methyladenine DNA glycosylase II (Gly II) on these adducts, calf thymus DNA was modified with [14C]sulfur mustard and used as a substrate for Gly II. Gly II releases both 3-hydroxyethylthioethyl adenine and 7-hydroxyethylthioethyl guanine from this substrate.

A 32P-postlabeling method for the detection of adducts in the DNA of human fibroblasts exposed to sulfur mustard.

Since the toxicities of sulfur mustard are attributed to DNA alkylation, levels of DNA modification in exposed cells should correlate with the intensity of exposure. We have found that 32P-postlabeling can be used successfully to detect the major adduct, 7-hydroxyethylthio- ethyldeoxyguanosine 5'-phosphate (HETEpdG), that is formed in DNA by sulfur mustard. This method has been used to establish a correlation between exposure and adduct formation in human fibroblasts grown in cell culture and exposed to sulfur mustard concentrations between 2.