Showing papers by "National Institutes of Health published in 1974"
TL;DR: The purification of homogeneous glutathione S-transferases B and C from rat liver is described, and only transferases A and C are immunologically related.
16,953 citations
TL;DR: The high sensitivity of this method permits detection of the small amounts of cyclic AMP formed at low enzyme concentrations or at early time points in kinetic studies.
3,935 citations
TL;DR: The data suggest that diabetes is another discrete cause of congestive heart failure and that some form of cardiomyopathy is associated with diabetes, as a result of either small vessel disease or metabolic disorders.
Abstract: The incidence of congestive heart failure was determined in relation to prior diabetic status in 5,209 men and women aged 30 to 62 years followed up for 18 years in the Framingham study Men aged 45 to 74 years had more than twice the frequency of congestive failure as their nondiabetic cohorts, and diabetic women had a fivefold increased risk This excessive risk appears to be caused by factors other than accelerated atherogenesis and coronary heart disease Even when patients with prior coronary or rheumatic heart disease were excluded, the diabetic subjects had a four- to fivefold increased risk of congestive heart failure In women (but not men) with prior coronary disease, diabetes also imposed a threefold increased risk of congestive failure Furthermore, the increased risk of heart failure in the diabetic patients persisted after taking into account age, blood pressure, weight and cholesterol values as well as coronary heart disease Women with diabetes appeared to be especially vulnerable and, irrespective of coronary disease status, had twice the frequency of congestive heart failure as men The excessive risk of heart failure among diabetic subjects was confined to those treated with insulin The data suggest that diabetes is another discrete cause of congestive heart failure and that some form of cardiomyopathy is associated with diabetes, as a result of either small vessel disease or metabolic disorders
1,828 citations
TL;DR: Numerous methods are available for the graphical display of radioimmunoassay dose—response curves, for curve-fitting and dose interpolation, for statistical quality control, and for automation and computerization of data processing.
Abstract: Numerous methods are available for the graphical display of radioimmunoassay dose—response curves, for curve-fitting and dose interpolation, for statistical quality control, and for automation and computerization of data processing. The relative merits of these approaches are discussed. Minimal requirements for radioimmunoassay data-processing systems are presented. The features of an "ideal" system are discussed.
1,065 citations
1,005 citations
880 citations
TL;DR: In this article, Axelrod applied signal transduction theory to his research on the metabolic function of serotonin, even describing the pineal gland as a "neurochemical transducer."
Abstract: In this article, Axelrod applied signal transduction theory to his research on the metabolic function of serotonin, even describing
the pineal gland as a "neurochemical transducer."
847 citations
TL;DR: The two enzymic procedures yielded equivalent results with all tissues examined (brain, liver, muscle and polymorphonuclear leucocytes).
780 citations
TL;DR: This work has recently presented studies describing the probable location of phospholipid-binding site(s) in the MN-glycoprotein of the human red cell membrane and of plasma lipoproteins.
715 citations
TL;DR: A tumor cell line was derived from the fibrosarcoma of a 35‐year‐old Caucasian man who died without having received chemotherapy or radiotherapy, and an aberrant karyology with marker chromosomes was present.
Abstract: A tumor cell line was derived from the fibrosarcoma of a 35-year-old Caucasian man who died without having received chemotherapy or radiotherapy. The in vitro growth properties and transplantability into antithymocytic sera treated mice were characteristic of these malignant cells. An aberrant karyology with marker chromosomes was present. No virus particles were detected. Cancer 33:1027-1033, 1974. ERMANENT CELL LINES FROM ANIMAL TISSUES P were established as early as 1948.23 Most of these were originated from malignant tissues. Although a number of human cell lines have been established in vitro, very few fibrosarcoma cell lines have been described. As far as we are aware, there are reports of approximately eight cell lines derived from osteogenic sarcomas,1,4,Q,10,13,~1 two on rhabdomyosarcoma,12)26 three on liposarcoma,1.9.10 and one each on giant cell sarcomas,l Kaposi's sarcoma,* neurogenic sarcoma,26 synovioma,lO and fibrosarcoma.l The rest of the reported cell lines are all carcinomas. Only a few of these sarcoma cell lines have been fully studied and characterized. In this paper we describe the properties of a tumor cell line (HT1080) derived from a fibrosarcoma of a human male.
676 citations
TL;DR: It is concluded that the retinohypothalamic projection to the suprachiasmatic nuclei is essential for maintaining the entrainment to light of the circadian rhythm in pineal serotonin N-acetyltransferase activity in the rat.
TL;DR: In this paper, an isolated, vascularly perfused preparation of rat intestine extracted large amounts of glutamine (75 µmoles per hour), but no other amino acid, from a recirculated blood perfusate.
TL;DR: Theses studies suggest that in some patients the disease common variable hypogammaglobulinaemia may be caused or perpetuated by an abnormality of regulatory T cells which act to suppress B-cell maturation and antibody production.
TL;DR: The purification, by affinity chromatography, of an hepatic protein which retains the characteristic binding properties associated with the membranes is described, which indicates a high degree of aggregation in the final, water-soluble preparation.
TL;DR: In most populations with low cholesterol levels and a low prevalence of coronary heart disease, the intake of fat is low and the fat which is ingested is derived primarily from fish and vegetable oils, and in most populations exhibiting a high serum cholesterol in men, there is also a high prevalence of heart disease.
TL;DR: The specificity observed between the syngeneic TNP‐modified sensitizing and target cells is compatible with the hypothesis that the TNP is altering cell surface proteins which are controlled by genes within distinct regions of the H‐2 major histocompatibility complex, and that these proteins are conformationally changed so as to be immunogenic to syngenesic thymus‐derived lymphocytes.
Abstract: Spleen cells from B10 congenic mouse strains were cultured in vitro by a modification of the Mishell-Dutton technique with trinitrophenyl (TNP)-modified syngeneic spleen cells. Five days later, the effector cells generated were incubated with 51 Cr-labeled unmodified or TNP-modified spleen or tumor target cells, and the percentage of specific lysis determined. The results obtained using modified syngeneic as well as congenic target cells indicated that although TNP-modification of the target cells was necessary to obtain lysis, the cytotoxicity was not specific for TNP exclusively, but was primarily directed against modified syngeneic cell surface components which may or may not have included the TNP moiety as an integral part of the recognition unit. A number of criteria were used to demonstrate that the phenomenon was attributed to T cell-mediated cytotoxicity, and was not due to lymphocyte-dependent antibody (LDA). These included: (a) failure of TNP-lysine to block the effector phase; (b) lack of detectable LDA in the culture media; (c) failure of spleen cells from athymic nude donors to generate effector cells; (d) sensitivity of effector cells to rabbit anti-mouse brain serum; and (e) the generation of effector cells by cortisone-resistant thymocytes. The specificity observed between the syngeneic TNP-modified sensitizing and target cells is compatible with the hypothesis that the TNP is altering cell surface proteins which are controlled by genes within distinct regions of the H-2 major histocompatibility complex, and that these proteins are conformationally changed so as to be immunogenic to syngeneic thymus-derived lymphocytes.
TL;DR: The evidence that the outer membrane provides a permeability barrier that makes gramnegative bacteria less permeable than gram-positive bacteria to a large variety of molecules, which includes many drugs and antimetabolites is summarized.
Abstract: The envelope of gram-negative bacteria contains three structures that can be visualized in the electron microscope (FIGURE 1 ) and can now also be separated, which permits their analysis: an inner, or cytoplasmic, membrane that contains lipid and protein; a thin peptidoglycan layer; and an outer membrane that contains lipopolysaccharide (LPS), in addition to protein and lipid. Although gram-positive organisms also have a cytoplasmic membrane and peptidoglycan layer, the outer membrane is unique to gram-negative organisms and confers special properties upon them. This paper will summarize the evidence that the outer membrane provides a permeability barrier that makes gramnegative bacteria less permeable than gram-positive bacteria to a large variety of molecules, which includes many drugs and antimetabolites. This evidence is twofold: chemical, because it has been found that ethylenediaminetetraacetate (EDTA) both increases cell permeability and specifically alters the outer membrane by releasing LPS; and genetic, because some mutants altered in LPS structure exhibit permeability changes and others with increased permeability display outer membrane alteration. A tentative model of the structure of the outer membrane and the aspects of this structure that provide the permeability barrier will be presented. The barrier function of the outer membrane first became accessible to study when it was found that EDTA disrupts this function. In 1958, MacGregor and Elliker discovered that mutants of Pseudornonns nerziginosa resistant to quartenary ammonium compounds become sensitive when exposed to EDTA, and these workers correctly concluded that EDTA increased permeability to these compounds; this observation appears to have been ignored, probably because, as will be discussed below, EDTA alone is much more toxic to this organism than to other gram-negative bacteria. Soon thereafter, Repaske found that EDTA permits lysozyme action on several gram-negative bacteria.g Spheroplasts formed by this method are sensitive to actinomycin, a drug that normally cannot affect intact Escherichia coli:', 1 While pursuing this observation in my laboratory, I found that EDTA alone, without lysozyme, conferred subsequent sensitivity to actinomycin upon the cells,5 and I concluded that EDTA permits entry of the drug. This conclusion was verified by the finding that EDTA-treated, but not control, cells, could bind radioactive actinomycin and that other molecules normally excluded could also enter.'; The permeability increase is very general, as is expected for partial breakdown of a passive permeability barrier. Many substances normally excluded can enter many species of gram-negative bacteria after they are treated with EDTA (TABLES 1 & 2 ) . Of special interest to this conference is the wide range of drugs, unrelated either in their structure or their action, that can attack such
TL;DR: Evidence is presented that administration of glutathione‐like nucleophiles, such as cysteamine, protects mice from arylation of hepatic macromolecules, hepatic necrosis, and death caused by the reactive acetaminophen metabolite.
Abstract: Recent studies of acetaminophen‐induced liver damage in animals indicate that acetaminophen is converted in the liver to a chemically reactive arylating agent that normally is detoxified by conjugation with glutathione. When the dose of acetaminophen is large enough to deplete hepatic glutathione, however, there is extensive arylation of hepatic macromolecules and cell death. This paper presents evidence that administration of glutathione‐like nucleophiles, such as cysteamine, protects mice from arylation of hepatic macromolecules, hepatic necrosis, and death caused by the reactive acetaminophen metabolite. Additional studies indicate that glutathione may serve a similar protective function in man as in other animals. Thus, logical treatment of patients overdosed with acetaminophen might be based on cysteamine or other nucleophiles.
TL;DR: This study, the largest of its kind, permitted more precise and extensive determination of the CAD risk accompanying severe hyperbetalipoproteinemia than has heretofore been possible.
Abstract: Analysis of cardiovascular status in adult relatives of 116 kindred affected with familial hyperbetalipoproteinemia (type II hyperlipoproteinemia) was carried out to assess coronary artery disease (CAD) risk in relatives with type II (II) compared to unaffected family members. Over 90% of the 738 living relatives were interviewed by one investigator and 12 lead electrocardiograms were obtained. In these, and in 285 deceased relatives, physician and hospital records were utilized to determine CAD events by standard criteria. This study, the largest of its kind, permitted more precise and extensive determination of the CAD risk accompanying severe hyperbetalipoproteinemia than has heretofore been possible. CAD was diagnosed in 29.5% of II9s compared with 10.5% of normal relatives (N) ( P P P = .002). CAD death or myocardial infarction occurred in 10.1% of II9s compared with 1.8% of N9s ( P
TL;DR: In cat retina, rod bipolar terminials do not synapse on ganglion cells but on two types of amacrine cell (types I and II), which appears to play a special internuncial role between bipolars and ganglions in the rod system.
Abstract: In cat retina, rod bipolar terminials do not synapse on ganglion cells but on two types of amacrine cell (types I and II). Cone bipolars synapse directly on ganglion cells and on type I amacrines. The type II amacrine appears to play a special internuncial role between bipolars and ganglion cells in the rod system.
TL;DR: It is concluded that all three components plus tropomyosin are necessary to restore full Ca2+ sensitivity, and that this reconstitution can be accomplished by combining the individual components in the absence of urea.
TL;DR: The posterior hypothalamus (premammillary nuclei, caudal subdivision of the arcurate nucleus, posterior hypothalamic nucleus) contains norepinephrine and dopamine in relatively low concentrations, while the paraventricular and dorsomedial nuclei and the retrochiasmatic area are rich in norpinephrine.
TL;DR: Algebraic reconstruction techniques (ART) were introduced by Gordon et al. as mentioned in this paper for solving the problem of 3D reconstruction from projections in electron microscopy and radiology, where each projected density is thrown back across the higher dimensional region from whence it came, with repeated corrections to bring each projection of the estimate into agreement with the corresponding measured projection.
Abstract: Algebraic reconstruction techniques (ART) were introduced by Gordon et al. (1970) for solving the problem of three dimensional reconstruction from projections in electron microscopy and radiology. An X-ray photograph represents the projection of the three-dimensional distribution of X-ray densities within the body onto a two-dimensional plane. A finite number of such photographs taken at different angles allows one to reconstruct an estimate of the original 3-D densities. The ART algorithms for solving this problem have a simple intuitive basis. Each projected density is thrown back across the higher dimensional region from whence it came, with repeated corrections to bring each projection of the estimate into agreement with the corresponding measured projection.
TL;DR: Serotonin was unevenly distributed throughout all the brain stem areas examined, and the motor nerve nuclei seemed to contain more of the amine than the sensory nerveuclei.
TL;DR: X-irradiation of Chinese hamster cells at temperatures above 37°C results in enhanced killing response and hyperthermia also inhibits the repair of sublethal damage for temperatures up to ∼41°C, demonstrating a reduced capacity for sub lethal damage when cells are hyperthermic during irradiation.
Abstract: X-irradiation of Chinese hamster cells at temperatures above 37°C results in enhanced killing response. The magnitude of this thermal effect increases with increasing temperature and varies inversely with dose rate during the exposure of the cells to the combined effects of elevated temperature and ionizing radiation. Postirradiation incubation at an elevated temperature is also effective in enhancing the response but not preirradiation hyperthermia. Split-dose experiments demonstrate that hyperthermia also inhibits the repair of sublethal damage for temperatures up to ∼41°C. Above 41°C, lethal damage expression is enhanced as well. Fluctuations in the age-response structure of cells x-irradiated at 42°C are reduced, a result consistent with a reduced capacity for sublethal damage when cells are hyperthermic during irradiation.
TL;DR: A survey of the autopsy material of 45 clinically and histologically typical cases of mycosis fungoides revealed extracutaneous involvement in 32, or 71%, and the lymph nodes showed diagnosable M.F. in 24 of these 32 cases.
Abstract: A survey of the autopsy material of 45 clinically and histologically typical cases of mycosis fungoides (M.F.) revealed extracutaneous involvement in 32, or 71%. The lymph nodes showed diagnosable M.F. in 24 of these 32 cases. Viscera most commonly involved were, in order of decreasing frequency: lung, spleen, liver, kidney, thyroid gland, pancreas, bone marrow, and heart. Practically all organs and tissues of the body were found to be involved. Lesions of the lymph nodes and viscera have a characteristic, if not a specific cellular composition which closely resembles that of cutaneous lesions. The neoplastic cells are of lymphocytic origin. Among them, the hyperchromatic mycosis cells and the cells with convoluted, deeply indented, and cerebriform nuclei have considerable diagnostic value. They are usually essential for the differentiation of the cellular proliferation of M.F. from those of other malignant lymphomas. Mycosis fungoides is a pathologic as well as a clinical entity; the neoplastic cellular proliferation in both cutaneous and extracutaneous tissue is distinct and different from those of other lymphoid and histiocytic neoplasms which usually arise in extracutaneous sites, but occasionally also in the skin.