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L B Russell

Publications and source records attributed to L B Russell.

At least 145 records · Page 8Linked to original sources
PubMed1980

Use of the mouse spot test to investigate the mutagenic potential of triclosan (Irgasan DP300).

Triclosan, a chlorophenoxyphenol used in several commercial products, was tested in the mouse in vivo somatic mutation test (spot test) by intraperitoneal injection on day 9.25 or 10.25 postconception. Although the dose range tested overlapped the toxic, the frequency of presumed somatic mutations was not significantly greater in the experimental groups than in the methanol-injected controls; and the results rule out with 95% confidence a spot incidence 5 or more times greater than the control incidence. These findings fail to confirm the claim by Fahrig et al. (1978) that triclosan is mutagenic in the spot test.

Animals↗
PubMed1979

Sensitivity patterns for the induction of homeotic shifts in a favorable strain of mice.

In an effort to develop a prescreening system that is sensitive, is compatible with in-vivo administration of presumptive teratogens, and utilizes morphological endpoints, we are studying the induction of homeotic shifts in the axial skeleton. Our earlier work had demonstrated the existence of critical periods for certain such shifts, even though the (C57BL x NB)F1 hybrid used was not entirely suitable for this purpose. Using 100 R X-rays on successive days during the period of major organogenesis, we have now analyzed the sensitivity pattern of the BALB/c, since this strain normally straddles thresholds for the position of axial borders. Mortality, birthweight, and skeletal anomalies were analyzed, in addition to the homeotic shifts. --Day 9 1/4 postconception was clearly the most sensitive stage for the production of posterior shifts at the thoraco-lumbar border and the lumbo-sacral border, and for increases in the number of sternebrae and costo-sternal junctions. Anterior shift could be induced three days later, on day 12 1/4, but this was confined to only one of the four characters, the thoraco-lumbar border. There are a number of indications that, at given stages during the study period, BALB/c embryos correspond developmentally to chronologically somewhat earlier stages of two strains studied previously. The present results do not support the hypothesis that factors influencing the quantitative skeletal characters act by way of body size. --Since homeotic shifts can be produced by a number of mechanisms and are obvious indications that developmental interference has occurred, and since such shifts are easy to score and convenient to analyze quantitatively, our identification of a highly suitable strain and of stages of maximum sensitivity in this strain should aid in making the system useful in the prescreening for chemical teratogens.

Abnormalities, Drug-Induced↗
PubMed1979

Analysis of the albino-locus region of the mouse. I. Origin and viability.

Numerous specific-locus experiments designed to test the mutagenic effect of external radiation have yielded, in over 3,600,000 animals observed, altogether 119 presumed mutations involving the c locus. Of these, 55 were viable and albino (cav), 13 were viable and of various intermediate pigment types (cxv), four were subvital (cas and cxs), seven were neonatally lethal albinos (cal), 28 prenatally lethal albinos (cal); 12 died untested. All of the prenatally lethal and at least one of the neonatally lethal c-locus mutations (cal classes) are probably deficiencies that we have analyzed extensively in other experiments. Since absence of the locus mimics albino in phenotype, the intermediates (cxv and cxs groups) probably resulted from intragenic changes. The class of viable albino mutants (cav) might include, in addition to intragenic changes, some extremely small deficiencies. --The effects on viability of c-locus lethals (cal's) in heterozygous condition are not drastic enough to be perceived in stocks of mixed genetic background except in the case of the two longest known deficiencies and a few others. --Analysis of the relation between radiation treatment and type of c-locus mutants obtained shows that the relative frequency of viable mutations, for each germ-cell type, is greater for low-LET than for neutron irradiation; however, the difference for any individual cell type is not significant. The majority (66.7%) of mutations derived from X- or gamma-ray irradiated spermatogonia are viable, and the proportion of "intermediates" among these viables is similar to that among presumed spontaneous c-locus mutations. No significant dose-rate effect on the proportion of lethals could be demonstrated within the set of mutants induced by low-LET irradiation of spermatogonia. Although sets from other germ-cell stages are too small for statistical tests, the results for oocytes are similar, as far as they go. Furthermore, most of the c-locus mutations induced in spermatogonia, even by high-dose-rate X-ray or gamma irradiation, are of a type most likely to result from single-tract events (62% cxv, cxs, and cav; plus 16% presumed deficiencies not involving the closest marker). These results support the view that most of the reduction in mutation frequency at low dose rates is not due to a change in relative proportion of two-track and one-track ionizing events.

Animals↗
PubMed1979

Analysis of the albino-locus region of the mouse. II. Mosaic mutants.

Among 119 mutations involving the c locus that were recovered in the course of mouse specific-locus experiments with external radiations, 16 were found in mosaic, or fractional, mutants. The number of additional c-locus fractionals that could have occurred in these experiments and, for a variety of reasons, might not have been clearly identified, probably does not exceed the present number.-There was no evidence for radiation induction of the fractionals, and even those occurring in the irradiated groups may thus be assumed to be of spontaneous origin. Since only two mutations in the control groups were found in whole-body mutants, it appears that the bulk of spontaneous c-locus mutations are fractionals.-None of the mutations recovered in fractional mutants was homozygous lethal; 25% were viable intermediate alleles, and the remainder were albino-like mutants, all viable except for one subvital and one not tested.-Genetic tests of the fractionals indicated no major selection against the new mutations, either gametically or in the progeny.-For the group of fractionals as a whole, about one-half of the germinal tissue carried the mutation, indicating that the fractionals came from an overall blastomere population that was one-half mutant. Such a population could result from mutation in one strand of the gamete DNA, in a daughter chromosome derived from pronuclear DNA synthesis of the zygote, or in one of the first two blastomeres prior to replication. Since the mouse embryo does not stem from all of the cleavage products of the zygote, the frequency of fractionals observed underestimates the frequency of mutational events that result in two types of blastomeres.

Animals↗
PubMed1979

Analysis of the albino-locus region of the mouse. III. Time of death of prenatal lethals.

The stage at which homozygotes die was determined for 28 mutations (general symbol c*) at the albino (c) locus, of which 26 had earlier been found to be probably prenatally lethal. Within each of the mutant stocks, the uterine contents of c*/c(ch) females, made pregnant either by c*/c(ch) males ("Ex" series) or by c(ch)/c(ch) males ("Co" series), were examined between 13 and 17 days postconception. Altogether, 743 females were dissected and 7197 corpora lutea (representing ovulations) counted. In selected stocks, an additional 40 and 13 females were dissected on days seven or nine, respectively.-In each of the 26 presumed prenatally lethal mutants, there was a deficiency of living fetuses in the Ex, as compared with the Co, group. Overall, this deficiency was 23.6% (expectation, 25% c*/c*). All meaningful excesses were in numbers either of moles (death shortly before, during, or just after implantation), or of early preimplantation losses. Homozygotes in none of the mutant stocks die between days nine and 19 postconception. Of 24 c-locus mutants known to be deficiencies since they lack the closely linked Mod-2, 13 clearly kill before implantation, ten around implantation, and one neonatally. The c and Mod-2 loci and the region between them are not needed for intrauterine survival.-There are indications that the distinction between early-preimplantation death and implantation death may, in a general way, be related to length of the deficiency.

Animals↗
PubMed1979

Meiotic nondisjunction in the mouse: methodology for genetic testing and comparison with other methods.

Since trisomies produce adverse effects relatively late in development or even postnatally, they are an important component of the array of genetic damages that might be caused by environmental agents. Whole-chromosome aneuploidy (as opposed to breakage-derived aneuploidy) might come about secondarily from crossover depression, or could follow damage to the meiotic spindle or to kinetochores. For simplicity, the event-by whichever of the mechanisms-is referred to as meiotic nondisjunction (ND). A genetic method has been devised which is based on the facts that ND involving the sex chromosomes produces mostly viable mice, and that such exceptional animals can be externally recognized by the use of appropriate markers. The method is compared with the following other ND indicators: univalent and/or chiasma frequencies at M I; number of dyads at M II; extra sex chromosomes in spermatids; karyotypes in cleavage, morula, or blastocyst metaphases; and chromosome constitution of mid-gestation embryos. Some of the cytological endpoints are found to be unreliable. Various biological variables (germ-cell stage, sex, age) are examined with a view toward maximizing the chances for detecting induced nondisjunction. While experimental evidence on this question is equivocal, a consideration of the probable ND mechanisms suggests that the early spermatocyte (in stages including the premeiotic S phase) may be a favorable test object. The numerical sex-chromosome anomaly (NSA) method is useful not only in the study of ND but also in detecting breakage-derived chromosome losses induced in females, where the dominant lethal test is not easily applicable.

Animals↗
PubMed1979

In vivo somatic mutation systems in the mouse.

In an effort to meet the need for a fast and cheap in vivo prescreen for inherited mammalian point mutations, a somatic forward-mutation method, originally developed in an X-ray experiment, has more recently been tested in work with chemical mutagens. The method makes use of coat-color mutations because (a) the gene product is usually locally expressed, (b) mosaics can be detected with minimal effort, and (c) opportunities for making comparison with induction of germinal point mutations are greatest.--Following treatment of embryos that are heterozygous at specific coat-color loci, various induced genetic changes can result in expression of the recessive (RS) in clones derived from "mutant" melanocyte precursor cells. However, other events, such as decrease in the number of precursor cells, or disturbed differentiation, can also result in spots, which with careful classification can usually be distinguished from RS's on the basis of their location and color. When this is done, the relative RS frequencies for a series of compounds at least roughly parallel the relative spermatogonial mutation rates. The fact that easily measurable (though low) RS rates are obtained with compounds that have yielded negative results in spermatogonial tests is not surprising in view of the fact that RS's can be caused by several mechanisms besides point mutation.--In spite of the parallelism observed in one laboratory, the usefulness of the in vivo somatic mutation method as a prescreen could come to be doubted because of major discrepancies between results of similar experiments at different laboratories. However, it appears probable that at least some of these discrepancies are due to failure to discriminate between spots that probably resulted from melanocyte insufficiency and spots that resulted from expression of the recessive.--Reverse somatic mutation systems can potentially avoid some of the pitfalls of forward mutation systems. Such system are still in developmental stages.

Animals↗
PubMed1978

The political economy of federal health programs in the United States: an historical review.

In the 1960s the federal government of the United States added a wide range of new health programs--Medicare, Medicaid, health manpower training, occupational safety, and others--to its long-established support for biomedical research and hospital construction. Total federal health outlays rose from $5 billion in 1965 to almost $37 billion in 1975. This paper describes the legislative history of federal health programs and reports the recent trends in expenditures by functional category. The expenditures of major programs are related to the populations they serve and data are presented to document the enormous inflow of resources to medical care during the last 10 years. This inflow has been induced by the structural changes in the medical care market first set in motion by private health insurance, and accelerated by the new federal programs. Designing some way to control it is a major problem in health policy for the late 1970s.

Economics↗
PubMed1977

Validation of the in vivo somatic mutation method in the mouse as a prescreen for germinal point mutations.

The in-vivo somatic mutation method developed by us in an earlier X-ray experiment was tested for its usefulness in chemical mutagenesis work, specifically in the prescreening for germinal point mutations. In order to explore possible parallelisms, the 7 compounds chosen for study, as well as the genetic markers used, were those with which large-scale specific-locus mutation-rate experiments in germcells had been conducted in the past or were in progress. From 1--3 dose levels were tested for each compound. On day 10 1/4 after copulation of C57BL females with T males, a single injection of the test compound was administered, and about 2000 offspring altogether were subsequently scored for survival, morphology, and presence of spots of various types. In accordance with our earlier results we found 3 types of spots: white near midline ventral spots (WMVS) which probably result from killing of melanocyte precursor cells; spots resulting from misdifferentiation; and the remainder, which probably result from expression of the recessive by one of several mechanisms (RS). Induction of teratogenic effects, which were stage-specific rather than agent-specific, generally paralleled induction of WMVS's. Both are interpreted as resulting from cell killing. Induction of RS's did not always parallel induction of WMVS's, but roughly paralleled relative frequencies of specific-locus mutations induced in spermatogonia by the same compounds. Even though the in vivo somatic-mutation method probably detects genetic changes additional to point mutations, the results indicate that it may be a useful prescreen for germinal specific-locus mutations, provided care is taken to distinguish between the 3 types of spots, only one of which (RS) is indicative of expression of the recessive.

Animals↗
PubMed1977

The diffusion of hospital technologies: some econometric evidence.

This paper examines the diffusion of five hospital technologies that have spread widely since 1950: the postoperative recovery room, the intensive care unit, the respiratory therapy department, diagnostic radioisotope facilities, and electroencephalograph. The regressions show that the logistic function describes the diffusion of hospital innovations as well as it does the diffusion of innovations in other industries, that the rates of diffusion for these technologies fall within the range established by work on other industries, and that the rates for technologies that were not yet widespread in the middle 1960s increased with the advent of Medicare and Medicaid.

Costs and Cost Analysis↗
PubMed1976

Abnormal ornithine carbamoyltransferase in mice having the sparse-fur mutation.

Mice with the X-chromosomal sparse-fur (spf) mutation frequently have urinary bladder stones composed mostly of orotic acid, which was identified by the following criteria: ultraviolet and infrared absorption, spectra, chromatographic behavior, melting point, and reactivity in a specific color test. This clue led to the discovery that spf-bearing mice have an abnormal form of liver ornithine carbamoyltransferase (carbamoylphosphate:L-ornithine carbamoyltransferase, EC 2.1.3.3). Normal ornithine carbamoyltransferase has maximum activity at pH 7.6-8.0 and 80% of maximum activity at pH 10.0.

Alleles↗
PubMed1976

A mutant of Escherichia coli with an altered elongation factor Tu.

A previously isolated mutant of E. coli K12 HAK 88 [Kuwano, M., Endo, h & yamamoto, M. (1972) J. Bacteriol, 112, 1150-1156], contains a new protein that in two-dimensional gel electropherorgrams has the same molecular weight as normal elongation factor Tu, but whose isoelectric point is altered approximately 0.1 pH unit in the acidic direction. Peptide mapping, purification properties and the ratio of leucyl plus isoleucyl to methionyl plus cysteinyl residues of the normal elongation factor Tu protein and the new protein show a close similarity between the two. The mutation causing the altered electrophoretic mobility is located between argH and rif (79 min on the E. coli genetic map). These biochemical and genetic data indicate that strain HAK 88 has a mutationally altered tufB gene.

Chromosome Mapping↗
PubMed1976

Radiation-induced mutations at mouse hemoglobin loci.

In experiments designed to detect new mutations affecting hemoglobin, we irradiated the male or female parent in reciprocal crosses of two mouse strains that differ in alleles at the hemoglobin (Hba, Hbb) loci as well as at five other specific loci. Offspring were analyzed for hemoglobin properties (electrophoretic pattern, solubility, crystal pattern), serum albumin differences, erythrocyte lysis, reticulocyte count, and external appearance. Five hemoglobin variants were found among the mutants. In three, the genetic contribution from the irradiated father was not expressed with regard to the alpha-chain; one carried a tandem deuplication (the first known case in the mouse) involving Hbb; and one probably resulted from double nondisjunction of chromosome 7. The finding that major chromosome aberrations can mimic hemoglobin mutations indicates the need, in similar experiments, to follow F1 screening with thorough cytogenetic analysis. The variants in which there is nonexpression of the alpha chain may be the result of small deficiencies or of faults in transcription or translation. Mutation rates based on these three variants are not out of line with earlier specific-locus results, although confidence limits are still wide.

Anemia↗
PubMed1976

The diffusion of new hospital technologies in the United States.

Increases in the real resources used in hospital care have been an important cause behind rising hospital costs in the United States. Many of these resources have taken the form of new hospital technologies, and this paper begins by reviewing the trends in adoption of new hospital technologies over the years 1950-1974. The resource requirements, costs , and to the extent possible the patient benefits, of two of these technologies are then discussed in more detail: intensive care, a widespread facility with many variations, has been a major contributor to hospital costs; radiotherapy has been characterized by a succession of competing technologies. Regulatory efforts such as certificiate-of-need reviews would be more effective if they viewed hospitals as flexible collections of such technologies-with the costs and patient benefits of each to be weighed separately-rather than primarily in terms of numbers of beds. A national center to collect information on the separate technological functions of hospitals and make it available to interested groups would make a useful contribution to hospital regulation.

Costs and Cost Analysis↗