Considerations in designing and analyzing surgical adjuvant study in resected stage I and II carcinoma of the lung.
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Biomedical subjects
Publications and source records attributed to N C Sun.
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We have defined a medium (called Sun's modified Waymouth medium) that selectively cultures some rodent epithelial cells that are capable of using citrulline in place of arginine. A growth-response study of the ability of 47 different mammalian cell cultures (of mouse, rat, Syrian hamster, Chinese hamster, guinea pig, rabbit, monkey, and human origin) to use arginine or its biosynthetic precursors, ornithine, citrulline, or argininosuccinate, showed that all epithelial cells and some fibroblasts are capable of growing in citrulline medium; however, primary embryo fibroblasts and 12 established fibroblast cell lines derived from Syrian hamsters failed to grow. The citrulline medium also allowed selective outgrowth of epithelial cells, without contaminating fibroblasts, from Syrian hamster tracheal explants. This absolute nutritional difference between Syrian hamster epithelial and fibroblast cells allows citrulline medium to be used for selective cultivation of epithelial cells, which should be valuable for study of growth, differentiation, and malignant transformation of mammalian epithelial cells.
A prospective study of hemostatic abnormalities in 108 cancer patients was undertken at an oncology clinic in a university teaching hospital. Tests included Quick prothrombin time, activated partial thromboplastin time, thrombin time, platelet count, modified Ivy bleeding time, fibrinogen, fibrin degradation products (FDP), euglobulin lysis time, protamine sulfate test, and factor V, VII, VIII and X assays. Ninety-eight per cent of the patients had one or more abnormal coagulation tests. The commonest abnormalities were elevated fibrin degradation products and prolonged thrombin time. Thrombocytosis occurred in 57% of patients, hyperfibrinogenemia in 46%, thrombocytopenia in 11%, and non had hypofibrinogenmia. It is suggested that platelet count, fibrinogen concentration, and serum FDP assay are the most useful tests in assessing the hemostatic abnormalities in cancer patients, although thrombin time, factor V assay, and bleeding time may also be helpful. The peripheral blood smears of 53 patients were reviewed, and only one showed microangiopathic hemolytic anemia. The data illustrate that subclinical coagulopathy is relatively frequent in patients with malignancy.
This report describes the case of a patient who had a fever of unknown origin and granulomatous hepatitis. Numerous granulomas were present in sections from a bone-marrow biopsy and bone-marrow clot obtained as a part of the diagnostic evaluation. Subsequent serologic studies proved the patient had Q fever. The authors re-emphasize that a distinctive form of granuloma occurs in the bone marrow with Q fever and that Q fever should always be a consideration in the differential diagnosis of bone-marrow granulomas.
A simple method was developed whereby immunoperoxidase and immunofluorescence techniques were applied in consecutive steps to demonstrate the presence of two antigens in the same tissue section. This method was applied in three model, two antigens were shown: a) each (gastrin and pepsinogen II) inside one of two different cell types (gastrin (G) and antral peptic cells), b) each (kappa or gamma light chains) inside different cells of the same type (plasma cells); also, both (kamma and gamma light chains) inside the same cell (Reed-Sternberg cell), and c) both (pepsinogen I and II) inside the same cell (chief cell of oxyntic glands). The results could be viewed and photographed either simultaneously, when the antigens were in different cells, or sequentially, when the antigens were in the same cells.
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In the progeny of somatic cell hybrids formed by fusion of human lymphocytes and Chinese hamster mutant cells, a single human chromosome A2 was selectively retained when grown in appropriate medium. Spontaneous breakage of this chromosome in different hybrid subclones led to the assignment of the gene for galactose-1-phosphate uridyltransferase to the centromeric region of this chromosome (2q11 leads to 2q14). This gene is shown to be syntenic to the previously mapped genes for acid phosphatase 1 and malate dehydrogenase 1.
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Sixty-seven galactose negative (Gal minus) clones were established from survivors after treatment of Chinese hamster lung (V79) cells with 5-bromodeoxyuridine and black light. The mutational origin of these clonal isolates was inferred on the basis of the previously demonstrated mutagenic action of the combined treatment, persistence of the Gal minus phenotype in cell progeny in the absence of selection, conditional lethality of three isolates, interallelic complementation, and assignment of a homologous human gene to chromosome A2. In contrast to the parental cells, Gal minus mutants could not utilize exogenous galactose, mannose, fructose, galactose 1-phosphate, glucose 1-phosphate, or glucose 6-phosphate. Permeation of galactose into mutant cells appeared unimpaired. In intra- and interspecific cell hybrids, the mutation causing the Gal minus phenotype behaved like a recessive character. The pleiotropic nutritional response was due not to deficiency of any one specific enzyme in the Leloir pathway but to significant reduction in activities of phosphoglucomutase, NADP-dependent isocitrate dehydrogenase, and perhaps other enzymes. In temperature-sensitive Gal minus mutants grown at permissive temperature or in complementing intra- and interspecific cell hybrids, the activities of these enzymes were restored to normal levels, accompanied by a regained ability to use the particular hexoses or hexose monophosphates. We postulate that the change from Gal + to Gal minus phenotype in hamster cells could be due to mutations at a regulatory gene locus, or at a yet unknown locus with enzymic defect that causes secondary metabolic imbalances.
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Idiopathic postpartum renal failure is a syndrome of acute, rapidly progressive oliguria, azotemia, and microangiopathic hemolytic anemia occurring shortly after a normal pregnancy and usually terminating fatally. Of 25 patients described in the literature, 8 survived: 1 recovered almost normal renal function, 4 had renal functional impairment, and 3 required maintenance hemodialysis. This report concerns a patient who survived after nephrectomy, hemodialysis, and successful renal transplantation from a living related donor. Theoretic and experimental studies indicate that heparin, platelet inhibitors, and fibrinolytic agents should be beneficial if given early. If the disease progresses to the irreversible stage, nephrectomy and renal transplantation are warranted since the disorder does not seem to recur after transplantation.
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Plasminogen activator activity in blood vessels of various organs was determined in three untreated (control) male dogs and in two male dogs that received a continous infusion of canine brain thromboplastic emulsion for 2 weeks. Activator was measured by the speed and degree of lysis of fibrin films that were overlaid with slices of tissue. Depletion of vascular plasminogen activator occurred in the vena cava of treated dogs at the site of the tip of the catheter, which was surrounded by a clot. A decrease of activator was found in most organs and particularly in certain endocrine organs (thyroid, pituitary, and testis). Of organs that normally contained the most activator, the greatest depletion was found in the skin, lung, and penis. The wide variation of plasminogen activator activity in organs of normal dogs is described.
Somatic cell hybrids formed between galactose-negative mutant Chinese hamster cells and human lymphocytes were selected in galactose medium and analyzed for the concurrent presence of specific human chromosome(s) and human galactose-1-phosphate uridyltransferase. In one of the hybrid clones only a single human chromosome, A2, was consistently present when the hybrid cells were maintained in the selective medium, suggesting that the location of the structural gene for galactose-1-phosphate uridyltransferase is on this chromosome. Among subclones derived from this cell hybrid in the absence of selection, a complete concordance was demonstrated between the ability or inability to utilize galactose and the concomitant presence or absence of the human transferase and the A2 chromosome.
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Treatment of an aneuploid Chinese hamster cell line (V79) in tissue culture with 5-bromodeoxyuridine and black light, with or without prior exposure of cells to another mutagen, led to the isolation of auxotrophic mutants, each of which exhibits a specific nutritional requirement for glycine, uridine, purine, or for a combination of glycine, hypoxanthine, and thymidine. 61 mutants that could not use exogenous galactose were also isolated. Thus, this treatment functions as an inductive, but not as a selective, procedure for mutations in mammalian cells.