A new mutagenicity assay method for frameshift mutagens based on deleting or inserting a guanosine nucleotide in the beta-lactamase gene

The conventional method of site-directed mutagenesis was used to develop two Salmonella strains, JK-1 and JK-2, for detecting frameshift mutagens. The JK-1 strain was derived from Salmonella typhimurium TA1537 strain transformed by a mutant construct. A guanosine nucleotide was inserted between nucleotide residues 312 and 313 of the beta-lactamase gene. The JK-2 strain was obtained by the same procedure, but a guanosine nucleotide in position 315 of the beta-lactamase gene was deleted. The strains were tested with ten frameshift mutagens and the revertants were selected by ampicillin resistance. Representative mutagens including 2-nitrofluorene (2-NF), 2-acetylaminofluorene (AAF), 9-aminoacridine (9-AA), 2,7-diaminofluorene (2,7-DAF) and 2-methoxy-6-chloro-9-(3-(ethyl-2-chloro-ethyl)-aminopropylamino)acridine (ICR-170) were more potent in the JK-1 strain than the JK-2 strain, and the number of revertant colonies were dose related. Under the same conditions, the ampicillin test was more sensitive than the Ames test. Other types of compounds such as 2-methoxy-6-chloro-9-(2-chloroethylaminopropylamino)acridine (ICR-191), benzo[a]pyrene (BP), 4-nitroquinoline N-oxide (4-NQNO), hycanthone and aflatoxin B1 (AFB1) were not as mutagenic to these new strains. The method is quite promising for studying certain specific frameshift mutagens, but more chemical mutagens should be tested to validate its applicability and reproducibility in general use.     

A linkage analysis of D17S74 (CMM86) in thirty-five families with premenopausal bilateral breast cancer

We report here results of a linkage analysis of a marker in 35 families in which the proband had premenopausal bilateral breast cancer. This group is of particular interest given their high family risk and the question of etiological heterogeneity. Probands were ascertained from cancer registries in Los Angeles County and Connecticut and major hospitals in Montréal and Québec. Assuming no residual heterogeneity and summing lod scores over all families, we obtained strong evidence against tight linkage (e.g., lod score at theta = 0.000001 is -3.39). To address the issue of heterogeneity, we performed admixture and predivided sample analyses. Using an admixture model we were able to reject the hypothesis of no linkage versus that of linkage with homogeneity (P = 0.045). However, we were unable to reject the hypothesis of no linkage versus linkage with heterogeneity (P = 0.119) or to distinguish between linkage with homogeneity and linkage with heterogeneity (P = 0.500). Predivided sample analyses based upon age of onset, pathological characteristics, time between diagnoses of the breast cancers in each bilateral proband, and the span of ages at diagnoses within a family did not discriminate between apparently linked and unlinked families.     

Invasive or transcutaneous measurements of oxygen saturation and blood gases? An evaluation of pulse oximetry and transcutaneous measurement of PO2 and PCO2 during rest and exercise

Arterial and transcutaneous measurements of the oxygen saturation (SO2), the partial pressure of oxygen (PO2) and the partial pressure of carbon dioxide (PCO2 were compared during rest before and after cycling, and during submaximal and maximal exercise, in 12 adult patients with cystic fibrosis. SO2 was measured non-invasively using two different pulse oximeters (Radiometer and Ohmeda, respectively) and PO2 and PCO2 were registered with a transcutaneous electrode (Radiometer). The coefficients of correlation between arterial and transcutaneous values were respectively 0.95 (Radiometer) and 0.85 (Ohmeda) for SO2, 0.77 for PO2, and 0.75 for PCO2. On average the differences between arterial and transcutaneous values were small, but varied by 3-4% (2SD) for SO2, 2.0 kPa for PO2 and 1.0 kPa for PCO2. Our results indicate that pulse oximetry is a reasonably good way of detecting severe arterial hypoxemia during work, whereas the transcutaneous measurements of PO2 and PCO2 show such large variations that this method cannot be recommended for clinical use.     

Survivorship analysis of DKS instrumentation in the treatment of spondylolisthesis

This retrospective study analyzed the survivorship of DKS instrumentation and the clinical outcomes in 185 patients with spondylolisthesis. These patients were treated with Zielke DKS instrumentation for a mean followup period of 3.5 years. Eight (4.3%) patients had late removal of implants, 25 (14%) had rod breakage, three (1.7%) had screw breakage, and 16 (8.7%) had nut loosening. The survivor rate of DKS instrumentation was 96% within 3 months after operation, 80% at 2 years, and 61% at 5 years after surgery. One hundred sixty-three (88%) patients had solid posterolateral fusion, and 167 (90%) patients had good to excellent results. Adjacent instability developed in 18 (9.7%) patients. Although Zielke DKS instrumentation has a smaller rod and relatively insecure locking system between the rod and screw, it is an effective implant for the treatment of spondylolisthesis.     

Hypothalamic amenorrhea and hidden nutritional insults

Three variants of the 57.5 kDa human plasma proteinase inhibitor antithrombin, H1Q, H65C, and H120C, have been expressed in baby hamster kidney cells to permit assignment of the 1H NMR resonances from the three histidines and evaluation of the role of these histidines in heparin binding. The NMR assignments have enabled more definitive interpretation of previous NMR-based studies of human antithrombin to be made. Although resonances of all three histidines are perturbed by heparin binding, only histidine 120 plays a significant role in the heparin binding site. The perturbations of resonances from histidines 1 and 65 indicate proximity to the heparin binding site and consequent sensitivity to the presence of heparin.