Action of bleomycin on structural mimics of intermediates in DNA double-strand cleavage

Bleomycin-induced cleavage was examined in several nicked, gapped, or intact duplex DNA substrates, including a structure designed to mimic a proposed singly nicked intermediate in double-strand cleavage. This nicked structure appeared to correctly target the second cleavage event in the complementary strand, resulting in a blunt-ended double-strand break, similar to that induced directly by bleomycin alone in an intact duplex of the same sequence. A one-base-gapped structure was markedly less efficient in correctly targeting bleomycin attack in the complementary strand. The results are consistent with a model of bleomycin-induced double-strand cleavage in which the nick formed by the initial bleomycin attack serves to target secondary attack to a specific position in the complementary strand, resulting in a double-strand break with a defined geometry.     

Clinical utility of the polymerase chain reaction in the diagnosis of extrapulmonary tuberculosis

This study examines the diagnostic utility of the polymerase chain reaction (PCR) in 156 patients (five human immunodeficiency virus (HIV) seropositive) suspected of extrapulmonary tuberculosis. The results of PCR in 226 samples from 11 different sites were compared with the results of microscopy and culture. Positive culture results were predicted in 86% of samples by PCR but in only 31% by microscopy. Specificity of PCR was 92%. In cases with culture-proven tuberculosis, PCR identified all 11 microscopy positive cases and 19 of 24 (79%) of the microscopy-negative cases. In four patients, PCR excluded the diagnosis of tuberculosis in microscopy-positive samples, which were later shown to contain mycobacteria other than Mycobacterium tuberculosis or laboratory contaminants. In 20 patients (microscopy, PCR and culture negative) a trial of antituberculous drugs was given, but patients showed no improvement and treatment was stopped. In 17 patients, all culture negative (in nine PCR was positive, three of whom also had positive microscopy) the diagnosis was probable tuberculosis based on clinical findings and response to treatment. This polymerase chain reaction has a much higher sensitivity than microscopy and can facilitate therapeutic decisions for those with suspected extrapulmonary tuberculosis.     

The prevalence of hepatitis B surface antigen in commercially prepared plasma products

Commercially available lots of plasma derivatives prepared between 1957 and 1975 were tested for hepatitis B surface antigen (HBsAg) by radioimmunoassay. In all, 69 per cent of lots of plasma protein fraction, 40 per cent of factor IX concentrate, 20 per cent of normal serum albumin, 13 per cent of antihemophilic factor, 3 per cent of fibrinogen, and 0.7 per cent of immune serum globulin lots tested were HBsAg-positive. There was great variation in the prevalence of HBsAg-positive lots of each product among the different manufacturers, reflecting not only differences in methods of processing plasma, but also differences in donor populations. Those manufacturers relying upon volunteer donor plasma or placental source material demonstrated lower rates of HBsAg-positive lots of final products than those relying upon commercial donor plasma. There was a marked decrease in the prevalence of positive lots during the period 1971 to 1973, coincident with the onset of routine plasma donor screening for HBsAg. However, current requirements for plasma screening have not resulted in totally HBsAg-free plasma products. Use of more sensitive and more reliable tests for HBsAg will probably reduce contamination of plasma pools with HBsAg to undetectable levels. Despite HBsAg-status, however, the "high-risk" plasma products (fibrinogen, antihemophilic factor, factor IX concentrate) must still be considered capable of transmitting hepatitis and used only with the strictest indications.     

Dynamic behavior of hepatitis C virus in chronically infected patients receiving liver graft from infected donors

We studied the outcome of hepatitis C virus (HCV) infection in 14 patients with end-stage HCV-related liver disease who received HCV-positive liver allografts. Viral sequences specific for donor and recipient were established by direct sequencing of PCR products from the NS5 region and by single-strand conformation polymorphism. Within a few months after transplantation the donor strain took over the recipient strain in 8 patients while in 6 patients it was the recipient strain which ultimately prevailed. Donor and recipient were infected by identical genotypes in 6 donor/recipient pairs and by different genotypes in the remaining 8 pairs. Subtype 1b and type 1 (1a + 1b) became the predominant strains in all recipient/donor pairs in which they were present. Patients retaining their own strain were found to have significantly more active liver disease than those infected by the donor strain. We show that HCV superinfection and overtake phenomena occur in humans and suggest that genotypes 1b and 1 (1a + 1b) may possess replicative advantages over other genotypes. Furthermore, we provide evidence of the existence of interference preventing simultaneous continuous infection even by the same genotype strains. The development of active liver disease associated with recipient strain infection and mild or no disease associated with infection from the donor suggests various pathogenic abilities of different HCV strains.     

Influence of fumonisin B1, present in Fusarium moniliforme culture material, and T-2 toxin on turkey poults

Diets containing 300 mg fumonisin B1 (FB1)/kg of feed and 5 mg T-2 toxin/kg of feed singly or in combination were fed to female turkey poults (Nicholas Large White) from day of hatch to 21 d of age. When compared with controls, 21-d body weight gains were reduced 21% by FB1, 26% by T-2, and 47% by the combination. the efficiency of feed utilization was adversely affected by FB1 and the combination of FB1 and T-2. Relative weights (grams/100 g BW) of the liver and gizzard were increased in poults fed the FB1 and the combination diets; whereas, the relative weight of the pancreas was increased in all treated groups. All poults were scored for oral lesions using a scale of 1 to 4 (1 = no visible lesions, 4 = severe lesions). Oral lesions were present in all poults fed the T-2 diet (average score of 3.29) or the combination diet (average score of 3.54). Serum concentration of cholesterol was decreased and lactate dehydrogenase activity was increased in poults fed the FB1 and combination diets. The activity of aspartate aminotransferase and the values for red blood cells, hemoglobin, and hematocrit were increased only in poults fed the combination diet. Inorganic phosphorus concentration was decreased only in poults fed the combination diet. The increased toxicity in poults fed the combination diet for most variables can best be described as additive, although some variables not altered by FB1 or T-2 singly were significantly affected by the combination, indicating that the combination may pose a potentially greater problem to the turkey industry than either of the mycotoxins individually.     

A comparison of bond strengths of complete crowns using two types of cements and three cleaning agents

In the past, biomechanical investigations on the dorsal pelvic ring have generally been performed on a small number of cadaveric pelves in various non-standardized procedures. Significant differences in stability between different internal fixation methods of unstable pelvic ring fractures were not found. The experimental design presented here was based as closely as possible on the physiological loading of the pelvis in one-leg stance. This method made it possible to carry out standardized, reproducible tests on different osteosytheses of the sacroiliac joint. Furthermore, the suitability of artificial bones for such investigations can be assessed on the basis of a larger number of similar experiments on artificial and human pelves and the number of human pelves required for such studies could be reduced.