Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Specific effects on human neutrophils of antibodies to a membrane protein constituent of neutrophil receptors for chemotactic formyl-methionyl peptides

IgG and Fab were prepared from goat antisera to MP-2, the quantitatively predominant membrane protein constituent of human neutrophil receptors for chemotactic formyl-methionyl peptides. Only 10%–25% of the f-Met-Leu-Phe combining sites of MP-2 purified from neutrophil membranes that had been solubilized in Nonidet P40 exhibited binding constants similar in magnitude to those of the receptors in intact neutrophils, while the remainder of the sites retained a mean of 2% of the affinity of native receptors. Purified MP-2 elicited IgG antibodies predominantly to framework determinants, rather than the combining site, of the f-Met-Leu-Phe receptors. IgG antibodies, but not Fab, evoked the release of significant quantities of β-glucuronidase and lysozyme from neutrophils. Saturating concentrations of Fab bound to a mean of 65,000 determinants per neutrophil, as assessed with ¹²⁵I-Fab, but failed to stimulate neutrophil chemotaxis or chemokinesis, and inhibited by 15% or less the binding of [³H]f-Met-Leu-Phe to intact neutrophils. Fab of anti-MP-2 inhibited neutrophil chemotactic responses to f-Met-Leu-Phe by up to 80%, without influencing the responses to equally chemotactic concentrations of fragments of C5 and of leukotriene B₄. Preincubation of neutrophils for 2–30 min at 37° with concentrations of f-Met-Leu-Phe which suppressed significantly the number of receptors available to [³H]f-Met-Leu-Phe, increased the number of receptors detected by ¹²⁵I-Fab of anti-MP-2, while neither fragments of C5 nor leukotriene B₄ altered the number of receptors determined by either assay. Antibodies to non-combining site determinants of chemotactic peptide receptors provide a novel immunospecific probe for studies of the regulation of neutrophil chemotaxis.     

Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

We have sequenced and compared DNA from the ends of three human chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub- domains with entirely different patterns of homology to other chromosome ends. The distal regions contain numerous, short (<2 kb) segments of interrupted homology to many other human telomeric regions. The proximal regions show much longer (approximately 10-40 kb) uninterrupted homology to a few chromosome ends. A comparison of all yeast subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG repeats into distal and proximal sub-domains with similarly different patterns of identity to other non-homologous chromosome ends. Sequence comparisons indicate that the distal and proximal sub-domains do not interact with each other and that they interact quite differently with the corresponding regions on other, non- homologous, chromosomes. These findings suggest that the degenerate TTAGGG repeats identify a previously unrecognized, evolutionarily conserved boundary between remarkably different subtelomeric domains.      

Sulfidopeptide-leukotriene peptidases in pulmonary edema fluid from patients with the adult respiratory distress syndrome

The human pulmonary edema fluid concentrations of LTC₄ and of LTD₄ and LTE₄, derived peptidolytically from LTC₄, were assessed by radioimmunoassays of the mediators resolved by reverse-phase high-performance liquid chromatography. The mean pulmonary edema fluid concentration (± SD) of LTD₄ of 19.2±25.6 nM for 12 patients with the adult respiratory distress syndrome and of LTE₄ of 192±309 nM for 10 of the patients were significantly higher (P<0.005 andP<0.05) than those of 2.2±2.4 and 11.0±18.2 nM, respectively, for 10 patients with cardiogenic pulmonary edema, whereas the lower mean concentrations of LTC₄ were not significantly different for the two groups. Pulmonary edema fluid from five patients with adult respiratory distress syndrome, one with cardiogenic pulmonary edema, and one with an indeterminate syndrome contained similar concentrations of peptidoleukotriene peptidases. The LTC₄ and LTD₄ peptidolytic activities in ARDS fluids were 81 and 142 kD, respectively, by gel filtration. The extents of peptidolysis of [³]LTC₄ and [³]LTD₄ by 100 µl of pulmonary edema fluid attained respective mean maximum levels of 74.5±2.9% (N=5) and 37.7±10.2% (N=4) after 30 min at 37°C and were inhibited by serine-borate and by cysteine, respectively. The predominance of LTD₄ and LTE₄ over LTC₄ in states of altered pulmonary vascular pressure and permeability thus is attributable to two distinct peptidases.