Hemoglobin switching in sheep: characteristics of BFU-E-derived colonies from fetal liver

Two types of erythroid colonies were generated in vitro from sheep fetal liver cells. The first type consisted of single colonies of 8-256 cells that were well hemoglobinized by 4 days; these are thought to originate from CFU-E. The second type consisted of macroscopic colonies composed of several subcolonies that matured between days 3 and 8 in vitro. At maturity, each contained 256 to > 1000 cells that formed a discrete macroscopic cluster. The macroscopic colonies, not previously described in sheep, are thought to be derived from BFU-E. The characteristics of sheep BFU-E were defined and the production of fetal hemoglobin (HbF, alpha 1, gamma 2) and HbC (alpha 2 beta 2) was compared in colonies derived from CFU-E or BFU-E. Bursts developed at erythropoietin (epo) concentrations as low as 0.1 U/ml, although the number observed increased with epo concentration up to 10 U/ml. The number of bursts observed was approximately proportional to the number of cells plated. As shown by thymidine suicide, approximately 50% of both the BFU e and CFU-E were in S-phase when obtained from the fetus. BFU-E were smaller and partially separable from CFU-E after sedimentation at unit gravity. The beta c/gamma synthetic ratio in colonies derived from BFU-E was greater than in CFU-E-derived colonies. These data suggest that the capacity for generation of erythroblasts making HbC is greater in the earlier or more primitive erythroid stem cells in fetal liver.     

Nephrotoxicity of hexachloro-1:3-butadiene in the rat: The effect of age,sex, and strain

Adult male rats are less susceptible to hexachloro-1:3-butadiene-induced nephrotoxicity than adult female and young male rats. A single dose of 50 mg/kg hexachloro-1:3-butadiene (HCBD) ip in adult Alderley Park (Wistar-derived) females produced marked renal tubular necrosis and an increased plasma urea by 24 hr. Young male rats were also more susceptible to HCBD-induced nephrotoxicity; a dose of 25 mg/kg produced marked tubular necrosis and an increased plasma urea in 21-day-old rats, while a dose of 200 mg/kg was required to produce a similar response in adult males. p-Aminohippurate accumulation by thin slices of renal cortex from rats treated 24 hr previously with HCBD was reduced in adult but not in young male rats. HCBD was more toxic to young male rats (21 and 29 days old, LD50 57 and 96 mg/kg. respectively) than to adult males (7 weeks old, LD50 360 mg/kg). HCBD administration produced a more marked nephrotoxicity in 21-day-old rats treated with phenobarbital in their drinking water for 7 days than in rats of the same age not treated with phenobarbital. Associated with the increased susceptibility of female rats, renal nonprotein sulfhydryl content (NP-SH) was decreased in female but not in male rats 4 hr after HCBD administration. This decrease suggests conjugation of HCBD by the female rat kidney. The sex and age differences observed in nephrotoxicity due to HCBD are probably related to differences in hepatic and renal enzymes responsible for the detoxification and/or activation of HCBD. Fischer 344 rats were slightly more susceptible and Long Evans rats slightly less susceptible than the Alderley Park strain to HCBD-induced nephrotoxicity, although the differences were not as marked as those seen with age and sex.     

Toxicity of butylated hydroxytoluene in mouse following oral administration

Male Swiss--Webster mice were given 400 mg/kg of butylated hydroxytoluene ([methyl-14C]toluene) by stomach tube. Radioactivity was measured in plasma, lung, liver and kidney from 0.5 h to 10 days later. Radioactivity associated with butylated hydroxytoluene (BHT) or its metabolites was highest in plasma and all tissues examined between 1 and 12 h after administration. After 24 h, less than 1% of the administered dose remained in the lung, kidney or liver. One day after BHT, DNA synthesis in lung increased and, on days 3, 4 and 5, was 6--8 times as high as in controls. DNA content of the lungs almost doubled. Synthesis and net increase of pulmonary DNA were dose-dependent. If BHT was given orally following injection of one single dose of urethane, adenoma formation in lung was enhanced. It is concluded that BHT, given by stomach tube and in doses higher than 100 mg/kg, produces extensive cell proliferation in mouse lung and acts as a promoting agent in adenoma development.     

Radionuclide ventriculography: evaluation of automated and visual methods for regional wall motion analysis

Regional wall motion (RWM) abnormalities are sensitive indicators of left ventricular (LV) dysfunction, but quantitation of RWM with gated radionuclide ventriculography (RVG) has been limited, particularly in the left anterior oblique (LAO) projection. Regional LV performance was studied in 18 patients undergoing LAO RVG immediately prior to contrast ventriculography (CVG). Wall motion was analyzed by semiautomated and visual methods using several coordinate systems. For semiautomated methods, RVG and CVG wall motion were closely related in the two 90 degrees polar sectors at the apex and posterior wall (r = .85) and in the five 45 degrees polar sectors from midseptum through posterior wall (r = .82). The basal sectors on RVG had weak relationship to CVG, due to adjacent vascular structures. Semiautomated and visual grades for polar sectors on both CVG and RVG were closely related (r = .88- .94). Measured regional wall motion on LAO RVG compared favorably with near-simultaneous CVG in nonoverlapping portions of the LV and allowed objective quantitation of regional LV performance.     

Test pattern for video displays and hard-copy cameras

Members of a Subcommittee of the Society of Motion Picture and Television Engineers, with the cooperation of other professional societies, have developed specifications for an operational test pattern for evaluation of television monitors and film recording cameras used in medical diagnostic imaging. The purpose of this test pattern and the associated recommended practice is to provide the users of the medical diagnostic display systems with a comprehensive test for set-up, acceptance testing, and day-to-day operational checks. Details of the test pattern, examples of the system problems diagnosed by use of the pattern, and methods for optimizing display devices with the pattern are presented.     

Nephrotoxicity of hexachloro-1,3-butadiene in the mouse: The effect of age,sex, strain,monooxygenase modifiers,and the role of glutathione

Administration of a single ip dose of hexachloro-1,3-butadiene (HCBD) to adult male or female Alderley Park mice at 96 μmol/kg or above produced renal tubular necrosis of the pars convoluta and pars recta of the proximal tubule by 24 hr. Renal damage was also observed biochemically by the reduced accumulation of the organic anion (p-aminohippurate) and organic cation (tetraethylammonium) by renal slices and by an elevated plasma urea. The toxicity of HCBD to adult Alderley Park mice was similar for males and females. Young male mice (21 and 28 days old) were slightly more susceptible to HCBD-induced nephrotoxicity than adult (7-week-old) males. A strain difference in susceptibility to HCBD-induced renal damage was observed, the $\text{BALB}\text{c}$ strain being slightly more sensitive than $\text{C57BL}\text{10J}$, C3H, $\text{DBA}\text{2J}$, and Alderley Park strains. This strain difference was reflected in the lethality of HCBD to mice. Prior administration of the monooxygenase inducers, phenobarbitone or β-naphthoflavone, or of the monooxygenase inhibitor, piperonyl butoxide, did not alter the extent of renal damage produced by HCBD in male Alderley Park mice. However, HCBD produced a marked decrease in kidney but not liver nonprotein sulfydryl content in this strain of mouse, suggesting the formation of glutathione conjugates in the kidney. Administration of the glutathione or N-acetylcysteine conjugates of HCBD produced a marked renal tubular necrosis similar to that seen with HCBD. It is suggested that the mechanism of HCBD-induced nephrotoxicity in the mouse involves nonoxidative metabolism of HCBD in the kidney and that the cysteine conjugates formed are further metabolized to a nephrotoxic agent.