Hypermutability of mouse chromosome 2 during the development of x-ray-induced murine myeloid leukemia

In an effort to identify the precise role of a deletion at regions D-E of mouse chromosome 2 [del2(D-E)] during the development of radiation-induced myeloid leukemia, we conducted a serial sacrifice study in which metaphase chromosomes were examined by the G-banding technique. Such metaphase cells were collected from x-irradiated mice during the period of transformation of some of the normal hematopoietic cells to the fully developed leukemic phenotype. A group of 250 CBA/Ca male mice (10-12 weeks old) were exposed to a single dose of 2 Gy of 250-kilovolt-peak x-rays; 42 age-matched male mice served as controls. Groups of randomly selected mice were sacrificed at 20 hr, 1 week, and then at intervals of 3 months up to 24 months after x-irradiation. Slides for cytogenetic, hematological, and histological examination were prepared for each animal at each sacrifice time. An expansion of cells with lesions on one copy of chromosome 2 was evident in 20-25% of treated mice at each sacrifice time. The majority of such lesions were translocations at 2F or 2H, strongly suggesting hypermutability of these sites on mouse chromosome 2. No lesions were found in control mice. The finding leads to the possibility that genomic lesions close to 2D and 2E are aberrants associated with radiation leukemogenesis, whereas a single clone of cells with a del2(D-E) may lead directly to overt leukemia. The data also indicate that leukemic transformation arises from the cumulative effects of multiple genetic events on chromosome 2, reinforcing the thesis that multiple steps of mutation occur in the pathogenesis of cancer.     

The effect of the special instruction of bronchial asthma patients on the efficacy of their treatment

As the data collected in a survey we conducted show, a major part of the modern general practitioner's work continues to be in the field of family medicine. This fact is also confirmed by the results of other surveys of general practice today. Patients still appreciate their GPs as a source of good medical care and counseling for the whole family. Our own study has shown that most patients would even like to see an expansion of the GP's counseling activities. The duration of the doctor-family relationship extends over many years, and is frequently longer than a decade.     

An ex ante analysis on the use of activity meters for automated estrus detection: To invest or not to invest?

The technical performance of activity meters for automated detection of estrus in dairy farming has been studied, and such meters are already used in practice. However, information on the economic consequences of using activity meters is lacking. The current study analyzes the economic benefits of a sensor system for detection of estrus and appraises the feasibility of an investment in such a system. A stochastic dynamic simulation model was used to simulate reproductive performance of a dairy herd. The number of cow places in this herd was fixed at 130. The model started with 130 randomly drawn cows (in a Monte Carlo process) and simulated calvings and replacement of these cows in subsequent years. Default herd characteristics were a conception rate of 50%, an 8-wk dry-off period, and an average milk production level of 8,310 kg per cow per 305 d. Model inputs were derived from real farm data and expertise. For the analysis, visual detection by the farmer (“without” situation) was compared with automated detection with activity meters (“with” situation). For visual estrus detection, an estrus detection rate of 50% and a specificity of 100% were assumed. For automated estrus detection, an estrus detection rate of 80% and a specificity of 95% were assumed. The results of the cow simulation model were used to estimate the difference between the annual net cash flows in the “with” and “without” situations (marginal financial effect) and the internal rate of return (IRR) as profitability indicators. The use of activity meters led to improved estrus detection and, therefore, to a decrease in the average calving interval and subsequent increase in annual milk production. For visual estrus detection, the average calving interval was 419 d and average annual milk production was 1,032,278 kg. For activity meters, the average calving interval was 403 d and the average annual milk production was 1,043,398 kg. It was estimated that the initial investment in activity meters would cost €17,728 for a herd of 130 cows, with an additional cost of €90 per year for the replacement of malfunctioning activity meters. Changes in annual net cash flows arising from using an activity meter included extra revenues from increased milk production and number of calves sold, increased costs from more inseminations, calvings, and feed consumption, and reduced costs from fewer culled cows and less labor for estrus detection. These changes in cash flows were caused mainly by changes in the technical results of the simulated dairy herds, which arose from differences in the estrus detection rate and specificity between the “with” and “without” situations. The average marginal financial effect in the “with” and “without” situations was €2,827 for the baseline scenario, with an average IRR of 11%. The IRR is a measure of the return on invested capital. Investment in activity meters was generally profitable. The most influential assumptions on the profitability of this investment were the assumed culling rules and the increase in sensitivity of estrus detection between the “without” and the “with” situation.     

Quantitative aspects of the formation of a half chromatid chiasma as an intermediate product of genetic recombination in bacteriophages

Formal genetic consequences of generation and break-up of a half chromatid chiasma have been studied on the basis of a model with the symmetric exchange of two strands between parental DNA molecules. In recombination analysis, generation and break-up of this structure gives rise to a critical frequency R (zeta), which corresponds to recombination between two markers separated by a distance equal to the mean genetic length zeta of the hybrid region at the time of scission of the cross connection. The use of the distance zata as a natural unit of a genetic map is suggested. In the case of bacteriophage T4 under conditions of standard crosses the half chromatid chiasma is characterized by the value R (zata) equal to 3.0-10(-2), the structure acquiring with equal probability either of the two alternative isomeric configurations at the time of scission of the cross connection. About four per cent of the total number of mismatches as a result of break-up to the half chromatid chiasm were repaired.     

Effect of hypoxemia on the erythropoietic activity of organs during perfusion

Hypoxemia (45-minute) influence in vivo on erythropoietic activity of the kidney, liver, spleen, and sternum was studied by normoxemic perfusion of the isolated organs. The erythropoietic activity proved to increase after 6-hour perfusion of the liver; this confirmed the participation of this organ in the extrarenal secretion of the erythropoietic factor.     

Gigantic pseudomucinous cyst simulating inoperable malignant ovarian tumor

A new operation has been done on 11 patients with post-traumatic impassible prostatomembranous urethral strictures. Complications have been minimal. The disadvantages and difficulties with 2 other procedures are discussed.