Testing transposable elements as genetic drive mechanisms using Drosophila P element constructs as a model system

The use of transposable elements (TEs) as genetic drive mechanisms was explored using Drosophila melanogaster as a model system. Alternative strategies, employing autonomous and nonautonomous P element constructs were compared for their efficiency in driving the ry+ allele into populations homozygous for a ry- allele at the genomic rosy locus. Transformed flies were introduced at 1%, 5%, and 10% starting frequencies to establish a series of populations that were monitored over the course of 40 generations, using both phenotypic and molecular assays. The transposon-borne ry+ marker allele spread rapidly in almost all populations when introduced at 5% and 10% seed frequencies, but 1% introductions frequently failed to become established. A similar initial rapid increase in frequency of the ry+ transposon occurred in several control populations lacking a source of transposase. Constructs carrying ry+ markers also increased to moderate frequencies in the absence of selection on the marker. The results of Southern and in situ hybridization studies indicated a strong inverse relationship between the degree of conservation of construct integrity and transposition frequency. These finding have relevance to possible future applications of transposons as genetic drive mechanisms.     

Employee response to a company-sponsored program of colorectal and prostate cancer screening

Studies done in the mid-1970s documented increased risk for respiratory cancer and leukemia among employees in a chemical company manufacturing plant where chloromethyl ethers were used in production from 1948 to 1971. In the late 1980s, the company informed current and former employees about the results of follow-up studies which showed a moderation of risk of respiratory cancer and leukemia. New data showing elevated rates of mortality from colorectal, prostate, bladder, and pancreatic cancer in the population were also reported. Via mailed correspondence, the company made a no-cost program of colorectal and prostate cancer screening available to employees upon request; and information about bladder and pancreatic cancer was made available. Thirteen percent of employees in the population indicated interest in colorectal and prostate cancer screening (response). Thirty-one percent of these responders were screened (adherence). Multivariate analyses showed that education and length of employment in the plant were positively associated with response. Being white was positively associated with response for younger workers; while among older workers being male was positively associated with response. In terms of adherence, we found that older, more highly educated workers were more likely to have a screening examination. Findings indicate that employee participation in workplace-sponsored colorectal and prostate cancer screening can vary according to worker sociodemographic factors and length of employment in areas of potential exposure.     

Restriction polymorphism of the APOB locus in residents of the city of Tomsk

Restriction fragment length polymorphism (RFLP) of the apolipoprotein B locus was investigated in the population of Tomsk. The frequencies of alleles and haplotypes of polymorphic restriction sites XbaI, MspI, and EcoRI were determined. The parameters of linkage disequilibrium and polymorphism information content (PIC) were estimated. Comparative data on various regions of the world are shown.     

The x-ray morphometric characteristics of the spine in persons 50 and older

To specify shape of the vertebra in relation to age and sex, the authors studied roentgenomorphometric evidence upon examination of the thoracic and lumbar spine in 600 patients over 50. Vertebral deformities were found in 45.1 and 44.5% of the examined males and females, respectively. Changes corresponding to vertebral body fracture were recorded in 12.3% of the males and 15.3% of the females. Age-related trends in the frequency of various defects have been analyzed. The frequency differed in males and females.     

Toxoplasma lymphadenitis. Analysis of cytologic and histopathologic criteria and correlation with serologic tests

Fear reactions of rats given bilateral lesions to the septum, hippocampus, or amygdala were compared with those of rats given sham lesions, in 2 animal models of anxiety: the shock-probe burying test and the elevated plus-maze test. Septal lesions produced anxiolytic effects in both tests (i.e., an increase in open-arm activity and a decrease in burying), whereas hippocampal and amygdaloid lesions produced neither of these effects. On the other hand, hippocampal and amygdaloid lesions impaired rats' passive avoidance of the electrified shock-probe, whereas septal lesions did not. These dissociations suggest that limbic structures such as the septum, amygdala, and hippocampus exert parallel but distinct control over different fear reactions.     

Activation of the K-ras oncogene in colorectal neoplasms is associated with decreased apoptosis

BACKGROUND: Recent in vitro data indicate that the oncogenic effects of activated ras genes may be mediated, at least in part, through inhibition of apoptotic cell death. To examine this proposition in vivo, the relationship between mutations of the K-ras gene and the frequency of apoptosis was studied in a series of 69 sporadic colorectal neoplasms (11 adenomas and 58 carcinomas). METHODS: Mutations in codon 12 of K-ras were determined by a single tube, enriched polymerase chain reaction. Apoptotic cells in tumor sections were identified by in situ end-labeling of fragmented DNA, whereas levels of bcl-2 and p53 proteins were determined by immunohistochemistry. RESULTS: Tumors with mutant K-ras had a significantly lower apoptotic index than those with the wild-type allele (P < 0.05). They were also more likely to exhibit positive bcl-2 staining (P < 0.05). Adenomas showed significantly greater bcl-2 positivity than carcinomas (89% and 51%, respectively; P < 0.05). The frequency of apoptosis in these tumors was not related to either bcl-2 positivity or p53 status. CONCLUSIONS: These findings suggest that activation of K-ras in colorectal carcinoma may inhibit apoptosis and thus favor tumor progression. Alternatively, this association may reflect an accumulation of K-ras mutations in cells in which normal apoptotic pathways have been impaired.     

Potentiation of murine MCa-4 carcinoma radioresponse by 9-amino-20(S)-camptothecin

9-Amino-20(S)-camptothecin (9-AC) has demonstrated efficacy against several human cancer xenografts, including cancers of the colon, breast, lung, ovary, and stomach and malignant melanoma, and is currently undergoing Phase I clinical trials. In vitro data indicate that the addition of topoisomerase I inhibitors shortly after irradiation causes conversion of single-strand breaks to double-strand breaks, resulting in synergistic lethality to cultured log-phase or quiescent malignant cells. In our study, the efficacy of 9-AC as a potential radiosensitizing agent in vivo was assessed in C3Hf/Kam female mice bearing 7.6-8-mm MCa-4 mammary tumors implanted i.m. into the right posterior thigh. In one series of experiments to determine the dose dependence of 9-AC, mice were injected twice a week with either 0.5, 1.0, or 2.0 mg/kg 9-AC (total doses of 2, 4, and 8 mg/kg, respectively) either alone or 1 h before irradiation. In a second series of experiments, the schedule dependence of 9-AC was determined by giving a constant total dose of 4 mg/kg 9-AC once (2 mg/kg), twice (1 mg/kg every third day), or four (0.5 mg/kg every other day) times per week for 2 weeks, either alone or combined with radiation. The same radiation regimen was used in all experiments: 2-Gy fractions daily for 14 consecutive days, giving a total dose of 28 Gy to the tumor-bearing leg only. Tumor response was assessed by regrowth delay and dose modification factors (DMFs) obtained by comparing regrowth delay in the groups given 9-AC alone with those given the same dose of 9-AC and radiation. 9-AC significantly delayed tumor growth when combined with radiation, and this effect was dependent on drug dose; DMFs of 2.4 [95% confidence interval (CI), 2.0-3.1], 3.7 (95% CI, 3.1-4.6), and 3.3 (95% CI, 2.7-4.1) were obtained for groups treated with total drug doses of 2.0, 4.0, and 8.0 mg/kg 9-AC, respectively. In addition, the same total dose of 4 mg/kg 9-AC was more effective when given either twice or four times a week compared with once a week, giving DMFs of 2.8 (95% CI, 2.2-3.9), 2.6 (95% CI, 2.0-3.6), and 1.7 (95% CI, 1.3-2.4), respectively. The effect of 9-AC and radiation on normal tissue toxicity was assessed in two normal tissues, jejunum and skin, in separate groups of mice. Jejunal crypt cell survival was decreased in those mice given single doses of 9-AC ranging from 0.5-4.0 mg/kg and 12.5 Gy of total body radiation compared with those given 12.5 Gy of total body irradiation alone. The same regimen of drug and radiation did not modify acute skin reactions. These results suggest that 9-AC is an effective in vivo radiosensitizing agent when given in divided doses with fractionated irradiation. In addition, the gastrointestinal tract but not skin could be a critical target tissue for the use of 9-AC combined with radiation.     

The pharmacokinetics of Kefzol in patients with acute pancreatitis when administered intravenously and endolymphatically

Pharmacokinetics was studied of kefsole administered by intravenous and endolymphatic routes to patients (n = 23) with acute pancreatitis. The studies made showed that intravenous route for the drug administration makes for a quicker entering of the antibiotic into the peritoneal exudate. Apart from these reasons, endolymphatic antibacterial therapy does not appear to avert the development of complications involving pus-formation/discharging in acute pancreatitis and does not seem to be essential in the complex of therapeutic measures to be applied for treating the above patients.     

Surface enhanced Raman spectroscopy for characterization of structural characteristics of carbon chains in alpha1-acid glycoprotein and pseudoglycoproteins]

Surface-enhanced Raman scattering (SERS) spectroscopy was used to study the structure of carbohydrate chains in glycosylated forms of alpha 1-acid glycoprotein (AGP) and in pseudoglycoproteins obtained by transferring the carbohydrate chains of AGP to a polyacrylamide carrier. It was found that AGP-D glycoform and pseudoglycoproteins containing three or more glycans per molecule, which possess high immunomodulating activity, have a specific spatial organization of carbohydrate chains. This organization is maintained by the interaction of neighboring glycans with each other and does not depend on the nature of the carrier (whether it is polypeptide or polyacrylamide).