Identification of a tumor inhibitory factor in rat ascites fluid

A polypeptide which inhibits the growth of human carcinoma cells has been characterized from Novikoff rat ascites fluid. This tumor inhibitory factor co-purified with transforming growth factor activity through acid/ethanol extraction and Bio-Gel chromatography. The two activities were completely separated by reverse phase HPLC. The tumor inhibitory factor is heat stable and requires disulfide bonds for bioactivity. This factor inhibited the anchorage independent growth of the more differentiated human colon carcinoma cell lines but did not affect the less differentiated carcinoma cells. The presence of stimulatory and inhibitory activities in the same extracts suggests that the relative concentrations of these factors may be important in the control of cell growth.     

Tumor-host zinc metabolism the central role of metallothionein

Features of tumor and host zinc metabolism are described. Emphasis is placed on tumor-host interactions. Using the model of the Ehrlich ascites tumor in mice, one clear site of modulation of cellular zinc by the amount of nutrient zinc available in the host is a zinc-binding protein with the properties of metallothionein. The selective depletion of zinc from this protein is correlated with the loss of cell proliferation by tumors injected into zinc-deficient animals. The properties of isolated metallothionein are consistent with a role for it as a reactive pool of intracellular zinc which can be donated to apozinc proteins and other structures. The presence of the Ehrlich tumor in mice also perturbs their distribution of zinc: zinc leaves the plasma and is accumulated by liver in the form of newly synthesized zinc metallothionein. During host zinc deficiency, this redistribution is not observed. This may be caused not only by a lack of mobile plasma zinc, but also by an inhibition of the initiation of this host response at the site of the tumor in the peritoneum.     

Detection and Identification of Translocations by Increased Specific Nondisjunction in ASPERGILLUS NIDULANS

A meiotic technique for visual detection of translocations has been applied to ten mitotically identified interchanges, and three new translocations were discovered using this method. Testcrosses between "standard" strains and potential translocation strains-e.g. strains with newly induced mutants or descendants from translocation crosses-are inspected for the frequency of abnormal-looking colonies. In all heterozygous translocation crosses "abnormals" are increased at least tenfold compared to the average control level of 0.15%. Most of these are disomics, and can be recognized by their characteristic phenotypes. Each translocation produces a few specific types, since nondisjunction is increased mainly in the linkage groups involved in the translocation (50-100-fold over control values). Therefore, translocations were not only detected but often tentatively assigned to linkage groups from the analysis of the disomic progeny in crosses. In addition, this technique allows reciprocal and nonreciprocal translocations to be distinguished, since only the latter produce one-third phenotypically abnormal duplication progeny. While results are clearcut in most cases, occasionally problems are encountered, e.g. when morphological mutants segregate in crosses, or when other genetic factors which increase or reduce the frequency of nondisjunction are present in certain strains.     

Analysis of selection in populations observed over a sequence of consecutive generations

Summary A statistical model is presented for dealing with genotypic frequency data obtained from a single population observed over a run of consecutive generations. This model takes into account possible correlations that exist between generations by conditioning the marginal probability distribution of any one generation on the previously observed generation. Maximum likelihood estimates of the fitness parameters are derived and a hypothesis testing framework developed. The model is very general, and in this paper is applied to random-mating, selfing, parthenogenetic and mixed random-mating and selfing populations with respect to a single locus, g-allele model with constant genotypic fitness differences with all selection occurring either before or after sampling. The assumptions behind this model are contrasted with those of alternative techniques such as minimum chi-square or unconditional maximum likelihood estimation when the marginal likelihoods for any one generation are conditioned only on the initial conditions and not the previous generation. The conditional model is most appropriate when the sample size per generation is large either in an absolute sense or in relation to the total population size. Minimum chi-square and the unconditional likelihood are most appropriate when the population size is effectively infinite and the samples are small. Both models are appropriate when the samples are large and the population size is effectively infinite. Under these last conditions, the conditional model may be preferred because it has greater robustness with respect to small deviations from the underlying assumptions and has a greater simplicity of form. Furthermore, if any genetic drift occurs in the experiment, the minimum chi-square and unconditional likelihood approaches can create spurious evidence for selection while the conditional approach will not. Worked examples are presented.This study was supported in part by the U. S. Atomic Energy Commission, Contract AT (11-1) -1552 to the Department of Human Genetics (CFS), University of Michigan, and by National Science Foundation Grant BMS 74-17453 awarded to the author.     

Isolation and biochemical characterization of folate deficient mutants of Chinese hamster cells

This article describes the selection of auxotrophic mutants of Chinese Hamster Ovary (CHO) cells and the genetic and biochemical characterization of two mutant lines. AUXB1 is auxotrophic for glycine, adenosine, and thymidine (GAT-), whereas AUXB3 requires only glycine and adenosine (GA-). These mutants do not complement since hybrid cells formed between them are also auxotrophic. Experiments concerned with the reversion of AUXB1 to prototrophy suggest that a single genetic lesion is responsible for the multiple auxotrophy. Biochemical analysis indicates that the multiple auxotrophy of both AUXB1 and AUXB3 is a result of low levels of intracellular folates in mutant cells. Phenotypic reversion to complete or partial prototrophy can be accomplished by growing these cells in high concentrations of folic or folinic acids. However, neither the folate transport nor the dihydrofolate reductase are defective in mutant cells. Chromatographic analysis of intracellular folate derivatives indicates that while folates extracted from wild type cells exist almost exclusively as polyglutamyl derivates (primarily pentaglutamates), AUXB1 cells contain primarily folate derivates in monoglutamyl form and AUXB3 cells contain mono-, di-, and perhaps some triglutamates. This observation suggests that the enzyme responsible for linking glutamate residues onto intracellular folate derivates is the site of the biochemical lesion in the mutant cells. Our results also suggest that a possible function of polyglutamyl residues is to aid cellular retention of folates.     

Isolation of salt-soluble elastin from ligamentum nuchae of copper-deficient calf

This paper describes the isolation and amino acid analysis of un-cross-linked elastin obtained by neutral salt extraction from the ligamentum nuchae of a calf fed from birth to 9 months on a diet low in copper.     

A collection of maize from Darien,Panama

A collection of maize obtained from the Chocó Indian tribe of Darien, Panama, differs from published accounts of maize reported as typical for the area in size and in methods of cultivation. The collection may represent a segregating population from crosses occurring between the racesChococeño andCoastal Tropical Flint. Implications of this hypothesis with regard to problems of introduction, present geographical occurrence, and transportation of these races by nomadic human vectors are briefly discussed.     

Psychological Sequelae of Accidental Injury: A Medico-Legal Quagmire

Litigation for personal injury following accidental trauma is an expensive and confused process involving three protagonists: patient, doctor and lawyer. Although post-traumatic conditions can be elaborately classified, the intrinsic validity of such classifications is often questionable. Current methods of evaluating psychological sequelae of accidental injury are inaccurate and unsatisfactory, partly because of the protagonists'' conceptual, motivational and semantic differences. In addition, there is no really satisfactory method of (a) determining and quantifying minor but significant degrees of brain damage, (b) distinguishing these from “post-traumatic neurosis”, or (c) determining the relationship between the trauma and subsequent disturbance of function. Increasingly “expert” advice is solicited but owing to the nature of the data and conditions of examination, such advice does little to clarify the underlying problems. Furthermore, doctors are often unable to communicate effectively to the judiciary just how the trauma has affected the patient. Even though certain suggestions for improvement are advanced, the need for comprehensive, longitudinal research is inescapable.