Showing papers by "University of California, San Francisco published in 1969"
TL;DR: The hypothesis that contemporary organisms are also randomly constructed molecular automata is examined by modeling the gene as a binary (on-off) device and studying the behavior of large, randomly constructed nets of these binary “genes”.
4,250 citations
TL;DR: Cytoplasmic vacuolization in a small percentage of cells and potassium loss are the only indications of cell injury detected, and the isolated cells are comparable to normal hepatic parenchymal cells in situ in appearance and function.
Abstract: A new technique employing continuous recirculating perfusion of the rat liver in situ, shaking of the liver in buffer in vitro, and filtration of the tissue through nylon mesh, results in the conversion of about 50% of the liver into intact, isolated parenchymal cells. The perfusion media consist of: (a) calcium-free Hanks' solution containing 0.05% collagenase and 0.10% hyaluronidase, and (b) magnesium and calcium-free Hanks' solution containing 2 mM ethylenediaminetetraacetate. Biochemical and morphologic studies indicate that the isolated cells are viable. They respire in a medium containing calcium ions, synthesize glucose from lactate, are impermeable to inulin, do not stain with trypan blue, and retain their structural integrity. Electron microscopy of biopsies taken during and after perfusion reveals that desmosomes are quickly cleaved. Hemidesmosome-containing areas of the cell membrane invaginate and appear to pinch off and migrate centrally. Tight and gap junctions, however, persist on the intact, isolated cells, retaining small segments of cytoplasm from formerly apposing parenchymal cells. Cells which do not retain tight and gap junctions display swelling of Golgi vacuoles and vacuoles in the peripheral cytoplasm. Cytoplasmic vacuolization in a small percentage of cells and potassium loss are the only indications of cell injury detected. By other parameters measured, the isolated cells are comparable to normal hepatic parenchymal cells in situ in appearance and function.
4,183 citations
TL;DR: Intercistronic complementation was observed between three classes of restriction and modification mutants of E. coli B, indicating that at least three cistron (the ram cistrons) are involved in the genetic control of the [restriction and modification of DNA].
3,656 citations
TL;DR: The kinetics and tissue distribution of the microsomal heme oxygenase suggest that it is of major importance in the physiological degradation of hemoglobin and other hemoproteins to bile pigment.
1,315 citations
TL;DR: Three distinct RNA polymerase activities have been isolated from developing sea urchin embryos, and in rat liver nuclei there are two RNA polymerases activities.
Abstract: Three distinct RNA polymerase activities have been isolated from developing sea urchin embryos. In rat liver nuclei there are two RNA polymerase activities. One polymerase (I) is probably localized in the nucleolus and one (II) in the nucleoplasm.
895 citations
TL;DR: There was evidence that values for flow to each ventricle, the atria and the septum were correct and the ratios of flow to radioactivity in myocardium and arterial blood should be equal if microspheres are well mixed in the aortic root and are distributed regionally in proportion to flow.
Abstract: Total and regional coronary blood flow were measured in dogs by left atrial injection of carbonized microspheres labeled with different radioactive isotopes (mean diameter 14 to 6lfi). Simultaneously blood was collected at 20 ml/min from a catheter tied into a peripheral artery. The ratios of flow to radioactivity in myocardium and arterial blood should be equal if microspheres are well mixed in the aortic root and are distributed regionally in proportion to flow. This was proved in seven right heart by-pass experiments where coronary venous drainage was measured directly. Also, less than 0.1% of total myocardial radioactivity appeared in coronary venous blood, even with hypoxemia and small microspheres. Total coronary flow in seven conscious dogs averaged 95 to 150 ml/min/100 g heart; and flow to the left ventricle was 111 to 169 ml/100 g. Although not validated independently, there was evidence that values for flow to each ventricle, the atria and the septum were correct. The radioactivity per gram of left ventricular subendocardial muscle was 2.5 times that of subepicardial muscle using microspheres 51 to 61yx in diameter, but the ratios were 1.4 and 1.3 using microspheres of mean diameters 20 to 23/i, and 14/i, respectively. It is unlikely that any of these microspheres measure blood flow to small portions of the ventricle.
712 citations
TL;DR: The data suggest that the neutrophils can play an important role in resistance to Candida infection and that the lysosomal enzyme myeloperoxidase and its oxidant substrate hydrogen peroxide are the major participants in neutrophil candidacidal activity.
Abstract: A quantitative assay of candidacidal activity based on differential staining of non-viable Candida albicans by methylene blue was developed and applied to studies of leukocytes from normal individuals and patients with fungal and other infections. Serum factors were necessary for optimal phagocytosis of C. albicans but lacked direct candidacidal activity. Normal human neutrophils (38 studies) killed 29.0 +/- 7.4% of ingested C. albicans in 1 hr. Eosinophils and monocytes killed a smaller percentage. Neutrophil candidacidal activity did not require protein or ribonucleic acid synthesis by the leukocyte but was inhibited by anaerobic conditions, potassium cyanide, and colchicine. Leukocytes of a patient with hereditary myeloperoxidase deficiency and of three children with chronic granulomatous disease phagocytized C. albicans normally, yet failed to kill them. Our data suggest that the neutrophil can play an important role in resistance to Candida infection and that the lysosomal enzyme myeloperoxidase and its oxidant substrate hydrogen peroxide are the major participants in neutrophil candidacidal activity.
537 citations
498 citations
403 citations
TL;DR: The data suggest that the fetomaternal transfer of lymphocytes is common, happens at least as early as the 14th week of gestation, and may be a consequence of transplacental migration of circulating fetal lymphoid cells, as well as leakage of blood.
374 citations
TL;DR: The resultant glass solution is believed to represent a new class of physical modification of drugs exhibiting strikingly fast dissolution rate of griseofulvin.
TL;DR: The findings suggest that mvb vesicles in epididymal epithelium are not lysosomes and are not involved in protein uptake, suggesting that a minority are derived from the mvB-limiting membrane.
Abstract: To investigate the origin and nature of vesicles found within multivesicular bodies (mvb), the cytochemical staining properties of mvb vesicles were compared with those of other cytoplasmic vesicles, i.e. those associated with the Golgi complex and endocytic vesicles found near the apical cell surface. Rat epididymal tissue was stained in unbuffered OsO4 for 40–48 hr, and the distribution of stain was compared to that of reaction products for acid phosphatase (AcPase) to mark lysosomal vesicles, or thiamine pyrophosphatase (TPPase) to mark certain Golgi vesicles, or infused with peroxidase (HRPase) to demonstrate endocytic vesicles. Mvb vesicles were stained only by OsO4; AcPase, TPPase, and HRPase reaction products stained the mvb matrix. OsO4 also stained certain vesicles along the convex surface of the Golgi complex. The findings suggest that mvb vesicles in epididymal epithelium are not lysosomes and are not involved in protein uptake. The majority of these vesicles have cytochemical reactions in common with vesicles located along the convex surface of the Golgi complex and may be derived therefrom. A minority are derived from the mvb-limiting membrane.
TL;DR: Peroxidases, functionally linked to hydrogen peroxide-generating systems, could provide phagocytic cells with the ability to kill many fungal species.
Abstract: In the presence of hydrogen peroxide and either potassium iodide, sodium chloride, or potassium bromide, purified human myeloperoxidase was rapidly lethal to several species of Candida. Its candidacidal activity was inhibited by cyanide, fluoride, and azide, and by heat inactivation of the enzyme. A hydrogen peroxidegenerating system consisting of d-amino acid oxidase, flavine-adenine dinucleotide, and d-alanine could replace hydrogen peroxide in the candidacidal system. Horseradish peroxidase and human eosinophil granules also exerted candidacidal activity in the presence of iodide and hydrogen peroxide; however, unlike myeloperoxidase or neutrophil granules, these peroxidase sources were inactive when chloride replaced iodide. Cells of Saccharomyces, Geotrichum, and Rhodotorula species, and spores of Aspergillus fumigatus and A. niger were also killed by the combination of myeloperoxidase, iodide, and hydrogen peroxide. Peroxidases, functionally linked to hydrogen peroxide-generating systems, could provide phagocytic cells with the ability to kill many fungal species.
TL;DR: This paper presents a general evaluation of the Danielli model, which is based on the observation that a thin membrane which controls evidence had been so compelling that the conclusion that there exists on the and its environment was led to.
Abstract: I. Introduction II. Problems in the characterization of biological membranes A. Structural characteristics B. Functional characteristics III. The models A. The Danielli or bilayer model 1. Evidence and arguments supporting the Danielli model 2. Evidence and arguments against the Danielli model 3. General evaluation of the Danielli model B. The subunit model 1. Possible categories of subunits a. Subunits of structure b. Subunits of function c. Subunits of assembly 2. Identification of subunits a. Morphological techniques b. Membrane fractionation techniques and reaggregation of membranes 3. Variations of the subunit model 4. Membranes for which a subunit structure has been postulated a. The inner membrane of mitochondria b. Halobacterium membranes c. Mycoplasma membranes d. Cell junction membranes e. Photosynthetic membranes f. Photoreceptor membranes of the eye g. Sarcoplasmic reticulum 5. General evaluation of the subunit model IV. Conclusions I. INTRODUCTION During the last 100 years permeability studies the exchange of water and solutes between the cell had led to the conclusion that there exists on the and its environment. The accumulated indirect surface of cells a thin membrane which controls evidence had been so compelling that the direct
TL;DR: The reversal of the normal relationship between CVo2 and MVo2 under these circumstances is compatible with the thesis that low output states are attended by redistribution of blood flow away from femoral, splanchnic, and renal circulation with preferential preservation of cerebral blood flow.
Abstract: Bedside catheterization of the right heart with a percutaneously introduced flowdirected catheter was carried out in 24 critically ill patients; 71 determinations of mixed venous oxygen saturation (MVo2) were obtained. A second catheter was inserted either into a central intrathoracic vein or the right atrium for simultaneous sampling of central venous (CVo2) or right atrial (RAo2) oxygen saturation. For the group as a whole, mean CVo2 (57.9% ± 15.25) was significantly greater than mean MVo2 (53.3% ± 14.84) (P<0.001), but there was no significant difference and correlation was good between changes in central venous compared to changes in mixed venous oxygen saturation. On the other hand, there was no significant mean difference as well as an excellent correlation between individual values of RAo2 and MVo2 (r=+0.95). Patients with heart failure or shock showed poor correlation between CVo2 and simultaneously determined MVo2. Furthermore, subjects with shock showed a mean CVo2 (58.0%±13.05) that was signifi...
TL;DR: X-ray diffraction analysis defines the spacings of membranes in retinal rod outer segments, and begins to suggest how rhodopsin molecules are arranged in the membranes.
Abstract: X-ray diffraction analysis defines the spacings of membranes in retinal rod outer segments, and begins to suggest how rhodopsin molecules are arranged in the membranes.
TL;DR: Injection of methanol solutions of trimethylanilinium salts of barbiturates, phenolic alkaloids, and dimethylxanthines produced thermal decomposition in the injection port to give methyl derivatives suitable for quantitative gas chromatography.
TL;DR: Ninety-nine young male Sprague-Dawley rats were used in a study of dimensional and metabolic changes incident to the placement of elastic bands between the maxillary first and second molars.
TL;DR: Human phosphofructokinase was partially purified from skeletal muscle and erythrocytes and showed greater affinity for DEAE-cellulose in Tris-phosphate buffer at pH 8, was more inhibited by ATP, and was less inhibited by citrate than muscle phosphofstructokinase.
TL;DR: Results indicate that glucose-6-phosphate dehydrogenase from a mouse oocyte is an X-linked enzyme, that its synthesis occurs in the oocyte and is dosage dependent, and that inactivation of the X chromosome does not occur in the mouse oocytes.
Abstract: The glucose-6-phosphate dehydrogenase and lactate dehydrogenase contents of oocytes from XO and XX female mice have been measured. The activity of the former in the oocytes of XO mice is half of that in the oocytes of XX mice, whereas the lactate dehydrogenase activities in the two groups of ova are the same. These results indicate that glucose-6-phosphate dehydrogenase from a mouse oocyte is an X-linked enzyme, that its synthesis occurs in the oocyte and is dosage dependent, and that inactivation of the X chromosome does not occur in the mouse oocyte.
TL;DR: Optic nerve ultrastructure was studied in nine humans and 11 monkeys and found that all axons of the optic nerve itself are myelinated, and blood vessels are confined to the connective tissue of the septa and the pia mater.
Abstract: Optic nerve ultrastructure was studied in nine humans and 11 monkeys. Unmyelinated nerve fibers, belonging to the peripheral nervous system, lie in the adventitia of the central retinal artery, but all axons of the optic nerve itself are myelinated. The ultrastructure of axons and glial cells is the same as elsewhere in the central nervous system. Astrocyte cell bodies and processes insinuate themselves among the nerve fibers and nerve fiber bundles. An astroglial layer lines all the neuroectodermal surfaces that abut upon connective tissue, such as the pia mater, the adventitia of the central retinal vessels, and the septa. Blood vessels are confined to the connective tissue of the septa and the pia mater. The vessels are mainly capillaries with nonfenestrated endothelium. Adjacent endothelial cells seem to be held together by zonulae occludentes (tight junctions).
TL;DR: The effects of infusions of saline, isoproterenol, calcium gluconate, and methoxamine suggested that viscous and inertial properties are also important determinants of diastolic left ventricular mechanics, and end-diastolic pressure often differed from that predicted by the exponential equation above, suggesting that it is not a reliable index of enddiastsolic volume and left Ventricular compliance.
Abstract: In 7 conscious dogs, left ventricular diastolic volume (V) was estimated by taking biplane cineradiographs with the left ventricular cavity previously outlined by permanent radiopaque markers. Left ventricular pressure (P) was measured with an implanted miniature transducer. There were two rapid filling periods during early and late diastole; little filling occurred during the middle third of diastole (diastasis). The diastolic pressure-volume relationship was approximately exponential and was fitted by the equation P = —a + be cY , where a, b, and c are positive constants; the relationship appeared to be determined principally by the elastic properties. The effects of infusions of saline, isoproterenol, calcium gluconate, and methoxamine suggested that viscous and inertial properties are also important determinants of diastolic left ventricular mechanics. No significant series viscosity was observed. Plastic properties were not detected. The elastic properties were not affected by agents having a positive inotropic effect. End-diastolic pressure often differed from that predicted by the exponential equation above, suggesting that it is not a reliable index of enddiastolic volume and left ventricular compliance.
TL;DR: The data obtained with acetylsalicylic acid indicate metabolism occurs in both the gut wall and in the liver, thereby causing a large reduction in the areas obtained after oral dosing or hepatic portal vein infusion when compared to the area obtained after infusion by the vena cava.
TL;DR: The syndrome of overwhelming postsplenectomy infection (OPSI) is unlike most fulminating bacteremias and septicemias in ordinary (spleen-containing) individuals, whereas the OPSI syndrome constitutes a distinct entity which often lasts only 12 to 18 hours.
Abstract: Splenectomy is a necessary remedial operation in a number of conditions in childhood; in others it is of questionable value. In traumatic rupture of the spleen, the necessity for removal of the organ is absolute and immediate; in aplastic anemia there is little need for haste and the possible benefit of the operation is doubtful. Between these extremes, there are several gradations (Table I). In the last 12 years, attention has been called to the greater frequency of sudden overwhelming infection in the splenectomized infants or children as compared to those with intact spleens. There are conflicting opinions about this danger. Some see no greater risk after splenectomy than after appendectomy; many others believe that the hazard is so specific as to contraindicate splenectomy in childhood, even when it might relieve acute or chronic hemolysis. The syndrome of overwhelming postsplenectomy infection (OPSI) is unlike most fulminating bacteremias and septicemias in ordinary (spleen-containing) individuals. Very few patients with bacteremia progress from good health to death in less than 24 hours, whereas the OPSI syndrome constitutes a distinct entity which often lasts only 12 to 18 hours. It may begin abruptly with slight sore throat, fever, and "feeling or looking sick," proceed to headache, vomiting, and hyperpyrexia; and be followed within a few hours by convulsions or coma and death. In the uncomplaining infant, the prodromata of spreading infection may be absent or missed. The pneumococcus is usually the invading organism. The meningococcus or influenza bacillus have also been blamed, but these infections last several days and are less fulminant.
TL;DR: Serumα1-antitrypsin, α1-acid glycoprotein, baptoglobin, ceruloplasmin and C-reactive protein are increased, albumin, transferrin, α-and β-lipoprotein are decreased as an early response to tissue trauma and inflammatory disease and in infection these changes are followed by a rise of γ-globulins.
TL;DR: The data presented indicate that this “labelled microsphere” method, despite some problems, is a sensitive and reliable way to study regional haemodynamic changes in the monkey.
Abstract: Investigations have been carried out to determine the reliability and validity of a method for making repeated measurements of the distribution of cardiac output, organ blood flow, and resistance in the unanaesthetized restrained rhesus monkey free from the influences of recent surgery. The data presented indicate that this “labelled microsphere” method, despite some problems, is a sensitive and reliable way to study regional haemodynamic changes in the monkey.
TL;DR: The over-all rate of mammalian cell DNA synthesis appears to be regulated primarily by the number of replicons in operation, and is only slightly, if at all, affected by differences in rate of chain growth along replicons.
TL;DR: Human polymorphonuclear neutrophilic leucocytes contain an abundance of myeloperoxidase, a lysosomal enzyme estimated to constitute between 2 and 5 per cent of the dry weight of theLeucocytes.
Abstract: NORMAL human polymorphonuclear neutrophilic leucocytes (PMN) contain an abundance of myeloperoxidase, a lysosomal enzyme estimated to constitute between 2 and 5 per cent of the dry weight of the leucocytes1,2. Although the enzyme has been purified and characterized, its contribution to the cellular economy has not been clearly defined. Recent investigations have suggested it participates in bactericidal processes3,4.