Late death of very low birthweight infants

The causes of 59 postneonatal deaths of very low birthweight infants were determined. Bronchopulmonary dysplasia (BPD) was the cause of 19 deaths. It also coexisted in 12/20 deaths from infection and 9/20 deaths from other causes. Improvement will be best achieved by advances in the prevention and treatment of BPD.     

Initiation and bidirectional propagation of chromatin assembly from a target site for nucleotide excision repair

To restore full genomic integrity in a eukaryotic cell, DNA repair processes have to be coordinated with the resetting of nucleosomal organization. We have established a cell-free system using Drosophila embryo extracts to investigate the mechanism linking de novo nucleosome formation to nucleotide excision repair (NER). Closed-circular DNA containing a uniquely placed cisplatin-DNA adduct was used to follow chromatin assembly specifically from a site of NER. Nucleosome formation was initiated from a target site for NER. The assembly of nucleosomes propagated bidirectionally, creating a regular nucleosomal array extending beyond the initiation site. Furthermore, this chromatin assembly was still effective when the repair synthesis step in the NER process was inhibited.     

Intra-amniotic infection and premature rupture of the membranes

Antiphospholid antibodies (APL) have a notable association with recurrent miscarriages, arterial and venous thrombosis and thrombocytopenia. Analysis of the potential pathogenic effects of such human antibodies has been hampered by the considerable difficulty in producing IgG as opposed to IgM monoclonal immunoglobulins. We have developed four human monoclonal IgG APL (LJ1, AH2, DA3 and UK4) by fusing the peripheral blood lymphocytes of three patients with SLE with a mouse human heteromyeloma cell line, CB-F7. These antibodies bind to a variety of anionic phospholipids, two (LJ1 and AH2) bind total histones but none binds to ssDNA or dsDNA. Binding to beta 2 GPI is non-specific. UK4 alone demonstrates lupus anticoagulant activity. All four have lambda light chains, two are IgG1 (AH2 and UK4) and two are IgG3 (LJ1 and DA3). These APL utilize VH genes present in the fetally restricted repertoire and multiple somatic mutations in the CDR suggest an antigen-driven process. In contrast, there is no restriction in V lambda gene usage and only one lambda chain is extensively mutated. Two clonally related hybridomas were isolated from a single patients. This supports the theory that clonal expansion is the mechanism whereby antigen selects high affinity mutations.     

Clinical evaluation--continuous real-time intra-arterial blood gas monitoring during anesthesia and surgery by fiber optic sensor

A clinical evaluation of the clinical utility, techniques of use, durability, accuracy, and potential complications of a newly available system for the continuous real-time, intra-arterial monitoring of arterial blood gas and acid base status (ABG) has been studied (Optex BioSentry System, Optex Biomedical, Incorporated, The Woodlands, Texas, U.S.A.). The system consists of three separate fiber optic channels with contained fluorescent and absorbant chemical analytes imbedded in a single probe and capable of insertion inside of a twenty gauge indwelling arterial catheter (The Optex Optode Sensor), along with an external monitor. The system was utilized during anesthesia and surgery in the care of five informed patients. Constant trend monitoring of all three variables was deemed satisfactory in four of the patients. The fifth sensor was damaged by a surgical assistant while in place and ceased to function. Comparison of Optode sensor readings with standard clinical laboratory ABG analysis was excellent in three uncomplicated patients (pH: bias -0.0183 pH units, precision: 0.0237 pH units; PCO2: bias 3.22 mmHg, precision 2.04 mmHg; PO2: bias -5.94 mmHg, precision 11.74 mmHg). Postoperative study suggested that discrepancies in a fourth patient may have been due to an incorrect 'offset' applied to the Optode sensor yielding a constant error.