Showing papers by "University of California, San Francisco published in 1971"
1,883 citations
TL;DR: It is shown that the purple colour is due to retinal bound to an opsin-like protein, the only protein present in this membrane fragment, which has been isolated in relatively pure form from Halobacterium halobium.
Abstract: HALOPHILIC bacteria require high concentrations of sodium chloride and lower concentrations of KCl and MgCl2 for growth. The cell membrane dissociates into fragments of varying size when the salt is removed1. One characteristic fragment—termed the “purple membrane” because of its characteristic deep purple colour—has been isolated in relatively pure form from Halobacterium halobium2. We can now show that the purple colour is due to retinal bound to an opsin-like protein, the only protein present in this membrane fragment (see also ref. 3).
1,849 citations
TL;DR: The findings indicate that the situation is basically the same as described previously in the rabbit, insofar as the origin, enzymic activity, and persistence in the mature cell of the two types of granules are concerned.
Abstract: Neutrophilic leukocytes (PMN) and their precursors from normal human marrow and blood were examined by histochemical staining and by electron microscopy and cytochemistry in order to determine the origin and nature of their cytoplasmic granules. Human neutrophils contain two basic types of granules, azurophils and specifics, which differ in morphology, contents, and time of origin. Azurophils are large and may be spherical or ellipsoid, the latter with a crystalline inclusion. They are produced in the first secretory stage (promyelocyte), contain peroxidase and various lysosomal enzymes, and thus correspond to modified primary lysosomes. Specifics are smaller, may be spherical or elongated, and are formed during a later secretory stage (myelocyte). They lack lysosomal enzymes and contain alkaline phosphatase and basic protein; their contents remain largely undetermined. Specifics outnumber azurophils in the mature PMN because of reduction in numbers of azurophils per cell by cell division in the myelocyte stage. The findings indicate that the situation is basically the same as described previously in the rabbit, insofar as the origin, enzymic activity, and persistence in the mature cell of the two types (azurophil and specific) of granules are concerned. The main difference between PMN of the two species is in the morphology (size, shape, and density) of the granules, especially the azurophils.
840 citations
TL;DR: Ass assessments have been made of the reliability of identification of sixteen standard head film landmarks in replicated tracings of the same head film, and the impact of the observed errors in landmark location on clinical decisions can be reduced through the routine use of replicated estimates for each landmark.
738 citations
TL;DR: The structure of the purple membrane and its localization in the bacterial cell envelope are described and it is shown that it contains retinal bound in a mole ratio of 1 : 1 to a protein of molecular weight 26,000 which is the only protein present.
Abstract: IN the preceding article1 it has been shown that a cell membrane fragment, the purple membrane, isolated from Halobacterium halobium2 contains retinal bound in a mole ratio of 1 : 1 to a protein of molecular weight 26,000 which is the only protein present. We now describe the structure of the purple membrane and its localization in the bacterial cell envelope.
413 citations
TL;DR: The forearm was used as the frame reference, and the palm, of which the thick stratum corneum is allegedly almost impenetrable, allowed approximately the same penetration as the forearm.
Abstract: Pesticides labeled with radioactive carbon (14C) (parathion, malathion, and carbaryl) were applied on the skin of volunteers. The experimental variable studied was the effect of anatomic site; all other factors (dose, solvent, and analytic method) remained constant. Quantitation was based on urinary recovery of the 14C. The forearm was used as the frame reference. The palm, of which the thick stratum corneum is allegedly almost impenetrable, allowed approximately the same penetration as the forearm. The abdomen and dorsum of the hand had twice the penetration of the forearm, whereas folliclerich sites, including the scalp, angle of the jaw, postauricular area, and forehead, had fourfold greater penetration. The intertriginous axilla had a fourfold to sevenfold increase; the scrotum allowed almost total absorption.
376 citations
357 citations
TL;DR: Results indicate that thyroid hormones stimulate NaK-ATPase activity differentially, which may account, at least in part, for the calorigenic effects of these hormones.
Abstract: In an earlier study, we proposed that thyroid hormone stimulation of energy utilization by the Na + pump mediates the calorigenic response. In this study, the effects of triiodothyronine (T 3 ) on total oxygen consumption ( Q O O2 ), the ouabain-sensitive oxygen consumption [ Q O O2 ( t )], and NaK-ATPase in liver, kidney, and cerebrum were measured. In liver, ∼90% of the increase in Q O O2 produced by T 3 in either thyroidectomized or euthyroid rats was attributable to the increase in Q O O2 ( t ). In kidney, the increase in Q O O2 ( t ) accounted for 29% of the increase in Q O O2 in thyroidectomized and 46% of the increase in Q O O2 in euthyroid rats. There was no demonstrable effect of T 3 in euthyroid rats on Q O O2 or Q O O2 ( t ) of cerebral slices. The effects of T 3 on NaK-ATPase activity in homogenates were as follows: In liver +81% from euthyroid rats and +54% from hypothyroid rats. In kidney, +21% from euthyroid rats and +69% from hypothyroid rats. T 3 in euthyroid rats produced no significant changes in NaK-ATPase or Mg-ATPase activity of cerebral homogenates. Liver plasma membrane fractions showed a 69% increase in NaK-ATPase and no significant changes in either Mg-ATPase or 59-nucleotidase activities after T 3 injection. These results indicate that thyroid hormones stimulate NaK-ATPase activity differentially. This effect may account, at least in part, for the calorigenic effects of these hormones.
357 citations
TL;DR: The rotatory contributions can be written as X = ΣfiXi, where the subscripts i = H, β and R represent the fractions of the helix, β-form and unordered form.
315 citations
TL;DR: Diffraction analysis of dispersions of membranes makes it possible to study membranes not in regular arrays and shows that a phospholipid bilayer is a predominant structural component of membranes with various different functions.
Abstract: Diffraction analysis of dispersions of membranes makes it possible to study membranes not in regular arrays. Such analysis shows that a phospholipid bilayer is a predominant structural component of membranes with various different functions.
295 citations
TL;DR: It is proposed that ATP participates in an early phase of enzyme degradation, and was shown, in the case of tyrosine aminotransferase, to be rapidly reversible and exerted by a mechanism different from the inhibition of protein synthesis.
TL;DR: The purpose of this investigation was to change a Class II molar relationship into neutral occlusion by reversing the effects demonstrated in the primate experiments, which indicate that the relative eruption of the posterior teeth is an important factor in the establishment of molar relationships.
TL;DR: It appears that the monocyte produces two types of primary lysosomes during different phases of its life cycle—azurophil granules made by developing monocytes in bone marrow or blood, and coated vesicles made by macrophages in tissues and body cavities.
Abstract: The origin, content, and fate of azurophil granules of blood monocytes were investigated in several species (rabbit, guinea pig, human) by electron microscopy and cytochemistry. The life cycle of monocytes consists of maturation in bone marrow, transit in blood, and migration into tissues where they function as macrophages. Cells were examined from all three phases. It was found that: azurophil granules originate in the Golgi complex of the developing monocyte of bone marrow and blood, and ultimately fuse with phagosomes during phagocytosis upon arrival of monocytes in the tissues. They contain lysosomal enzymes in all species studied and peroxidase in the guinea pig and human. These enzymes are produced by the same pathway as other secretory products (i.e., they are segregated in the rough ER and packaged into granules in the Golgi complex). The findings demonstrate that the azurophil granules of monocytes are primary lysosomes or storage granules comparable to the azurophils of polymorphonuclear leukocytes and the specific granules of eosinophils. Macrophages from peritoneal exudates (72–96 hr after endotoxin injection) contain large quantities of lysosomal enzymes throughout the secretory apparatus (rough ER and Golgi complex), in digestive vacuoles, and in numerous coated vesicles; however, they lack forming or mature azurophil granules. Hence it appears that the monocyte produces two types of primary lysosomes during different phases of its life cycle—azurophil granules made by developing monocytes in bone marrow or blood, and coated vesicles made by macrophages in tissues and body cavities.
TL;DR: A rapid, simple, one-step procedure is described for the separation of cyclic AMP from ATP, ADP, AMP, and P 1 based on selective adsorption of all nucleotides except cyclicAMP on hydrous aluminum oxide.
TL;DR: Results of the present study clarify the apparent discrepancies that exist between estimations of half-life based on clinical observation of pharmacologic effects of the drug and calculations made from limited clinical determinations.
Abstract: The use of intravenous (i.v.) lidocaine for the control of ventricular arrhthmias has made it necessary to learn more about the disposition kinetics of this drug, and from such information to establish effective and safe dosage regimens. The clinical observation of rapid onset but short duration of response (10-20 minutes) after a 50-mg or 100-mg bolus of lidocaine, together with the prompt termination of antiarrhythmic effects after discontinuing a prolonged i.v. infusion, has led to the assumption that lidocaine is readily eliminated from man.' The concentration of plasma or blood lidocaine determined up to one hour after an i.v. bolus declines with a half-life of 10-20 minutes.' Gianelly and associates3 found that patients with coronary heart disease who are given a constant i.v. infusion without an initial bolus achieved plateau concentrations in plasma within 30-60 minutes. This observation also suggested a half-life of between 10 and 20 minutes for the drug. These collective data from blood concentrations of lidocaine tend to confirm the observations made in therapeutic settings. Beckett and co-workers, however, reported that the half-life was 1.6-1.8 hours in normal subjects.' These investigators based their conclusion on the rate of urinary excretion of the unchanged drug while the urine was acidic. Only 4.1-7.2% of the unchanged drug was excreted in the urine. Excretion of lidocaine is influenced by urinary pH.' Beckett and colleagues' also proposed that deethylation of lidocaine to monoethylglycylxylidide was a major metabolic pathway in man. Apart from this proposal, very little is known about the metabolism of lidocaine in man, even though some information is available in animals.6 Results of the present study clarify the apparent discrepancies that exist between estimations of half-life based on clinical observation of pharmacologic effects of the drug and calculations made from limited clinical determinations. The disposition kinetics of lidocaine were studied in normal volunteers, and this information has helped establish suitable dosage regimens in patients with ventricular arrhythmias.
TL;DR: In this article, an abnormal lipoprotein was visualized directly in serum by electron microscopy of preparations negatively stained with potassium phosphotungstate, and the particle was shown to be a flattened vesicle, the wall of which is a continuous lipid bilayer.
Abstract: An abnormal lipoprotein was visualized directly in serum by electron microscopy of preparations negatively stained with potassium phosphotungstate. It appears as a unique disk-shaped particle with major axis measuring 400 to 600 angstroms and minor axis measuring about 100 angstroms. Chemical analysis, viscosity measurements, and x-ray diffraction analysis of purified preparations indicate that the particle, consisting of a one-to-one molar mixture of cholesterol and choline phosphatides associated with a small amount of protein, is a flattened vesicle, the wall of which is a continuous lipid bilayer.
TL;DR: Extracellular histamine stimulates accumulation of adenosine 3',5'-monophosphate in human leukocytes and prevents antigenic release of histamine from cells of allergic donors and both effects occur at histamine concentrations that can be achieved by antigenicrelease of the amine in vitro.
Abstract: Extracellular histamine stimulates accumulation of adenosine 3',5'-monophosphate in human leukocytes and prevents antigenic release of histamine from cells of allergic donors. Both effects occur at histamine concentrations that can be achieved by antigenic release of the amine in vitro.
TL;DR: It is concluded that synthesis of microtubular precursor protein is mediated by the mature centriole and that this protein is packaged into many condensation forms in order to allow the rapid assembly of a large number of centrioles in a brief period of time.
Abstract: The differentiating mouse oviduct has been used for the study of centriole morphogenesis because its epithelium is extensively ciliated and centriole formation occurs in a brief period after birth. Proliferative elements, consisting of an extensive fibrillar meshwork encrusted with 75 mµ granules, were encountered at all ages, but were the only centriole precursors present in younger animals (2–3 days). These large aggregates were found either physically associated with a mature centriole or alone, but never associated with procentrioles. It is likely, therefore, that although proliferative elements may be derived from preexisting centrioles, they do not directly produce new centrioles. An intermediate structure, the condensation form, found primarily in older animals (4–6 days), and produced by the packing of the proliferative element material, gives rise to daughter procentrioles. This association of procentriole and condensation form has been called a generative complex. Condensation forms undergo various stages of depletion, producing hollow spheres with thin walls or small osmiophilic aggregates as procentrioles grow in length and assemble their microtubules. From these observations it is concluded that synthesis of microtubular precursor protein is mediated by the mature centriole and that this protein is packaged into many condensation forms in order to allow the rapid assembly of a large number of centrioles in a brief period of time.
TL;DR: The primary structure of human pituitary growth hormone has been reinvestigated and it was found that a segment of the sequence containing the single tryptophan residue was misplaced and that two amino acid residues must be added to the original 188 amino acids in the HGH molecule.
TL;DR: The purified enzyme is active only against the HDLa and VHDL classes of plasma lipoproteins, and the protein moiety of these classes is required for the significant esterification of cholesterol in sonically dispersed lipid emulsions.
TL;DR: Two groups of patients underwent renal transplantation and were managed similarly in all respects, except for the dosage of corticosteroids administered post-operatively, which was approximately three times greater than that for the second group with 136 patients.
Abstract: Two groups of patients underwent renal transplantation and were managed similarly in all respects, except for the dosage of corticosteroids administered post-operatively. For the first group, sixty-eight in number, the dosage was approximately three times greater than that for the second group with 136 patients. Avascular necrosis of bone appeared in sixteen patients in the first group and in two in the second. A greatly increased incidece of avascular necrosis after repeated transplantations was noted.
TL;DR: A mutation which confers insensitivity to androgenic hormones causes a great decrease in the ability of kidney cytoplasmic receptors to bind dihydro-testosterone, which results in a lower nuclear uptake of the steroid.
Abstract: A mutation which confers insensitivity to androgenic hormones causes a great decrease in the ability of kidney cytoplasmic receptors to bind dihydro-testosterone. This results in a lower nuclear uptake of the steroid.
TL;DR: Although all cultures producing interferon showed some degree of transformation (thymidine-(3)H incorporation into deoxyribonucleic acid), no direct correlation between the degree of phytohemagglutinin-induced lymphocyte transformation and the interferons was observed.
Abstract: In studies of 13 normal adults to determine the blood cell types responsible for interferon production induced by phytohemagglutinin, the following observations were made. (a) In cultures containing 96-100% pure macrophages derived from blood monocytes, no interferon was detected in either the presence or the absence of phytohemagglutinin for up to 92 hr. (b) In cultures of 99.5-100% pure lymphocytes, low levels of interferon were detected in the presence, but not in the absence, of phytohemagglutinin. (c) An average fivefold increase in interferon titers occurred when pure lymphocytes were combined with the macrophages in culture with phytohemagglutinin. The peak response of interferon occurred at 68 hr after the initiation of the combined cultures. For maximum response, phytohemagglutinin was required for the duration of the culture, and both cell types in association were necessary. Medium from phytohemagglutinin-stimulated macrophages or lymphocytes could not substitute for the corresponding intact cell. However, frozen-thawed macrophages in combination with lymphocytes and phytohemagglutinin produced an intermediate interferon response. An increase in either cell type produced an increased response in the range studied: lymphocytes, 0.45-1.8 × 106 per ml; and macrophages, 0.5-2.1 × 105 per ml. Syngeneic fibroblasts, HeLa cells, or mouse macrophages could not substitute for the human macrophages in the combined cultures with phytohemagglutinin. (d) Although all cultures producing interferon showed some degree of transformation (thymidine-3H incorporation into deoxyribonucleic acid), no direct correlation between the degree of phytohemagglutinin-induced lymphocyte transformation and the interferon titers was observed.
The demonstration of macrophage-lymphocyte interaction in the production of interferon is of interest in view of the known interrelationship of these same cell types in antibody synthesis and cellular immunity.
TL;DR: The circulation was studied in 33 previable human fetuses delivered by hysterotomy, while the placenta was still attached, and there was a fairly uniform decrease in proportion of CO distributed to theplacenta, probably owing to umbilical vessel constriction.
Abstract: Extract: The circulation was studied in 33 previable human fetuses (12–272 g) delivered by hysterotomy, while the placenta was still attached. The umbilical vein (UV) and in some instances umbilical or carotid artery (FA) were cannulated. Fetal and maternal pH, PO2, and PCO2 were measured. Radionuclide-labeled microspheres (50 μ in diameter) were injected into the UV on one or more occasions from 1 to 36 min after delivery of the fetus. The distribution of the cardiac output (CO) was calculated from the relative amounts of radioactivity in each organ. In 11 fetuses, FA blood samples were withdrawn during microsphere injection, and CO and actual organ blood flows were measured. With advancing gestational age (10–20 weeks) there was an increase in total inferior vena caval return from 64 to 75% of CO. The proportion of CO to the placenta increased from 17 to 33% and to the gut from 5.5 to 9.2%. Superior vena caval return decreased from 32 to 23%, and the percentage of CO to the kidneys fell from 6.5 to 3.2%. In those fetuses in which repeated observations were made, there was a fairly uniform decrease in proportion of CO distributed to the placenta, probably owing to umbilical vessel constriction. This deterioration was not reflected by UV blood gases which in fact showed a decrease in PCO2 and rise of PO2, when FA showed a rise of PCO2 and fall in PO2 and pH. Associated with the fall in FA pH there was an increase in the proportion of CO to the brain, myocardium, and adrenals. The proportion of CO to the brain increased significantly with increase of FA PCO2. Speculation: The circulation of the previable human fetus may be studied at the time of hysterotomy. It is most important to realize that, even though umbilical venous blood gases may appear to reflect good physiological function, umbilical flow may be markedly decreased. This must be taken into account in all attempts to study placental function.
TL;DR: After brief consideration of the various kinds of contact dermatitis, the emphasis is on allergiccontact dermatitis.
TL;DR: Findings indicate that cells of the reticuloendothelial system, presumably including the Kupffer cells ofThe liver and the macrophages of the spleen, possess the enzymatic machinery for converting hemoglobin-heme to bilirubin.
Abstract: Recent studies have identified and characterized the enzymatic mechanism by which hemoglobin-heme is converted to bilirubin. Under physiologic conditions the enzyme system, microsomal heme-oxygenase, is most active in the spleen followed by the liver and bone marrow, all of which are tissues that normally are involved in the sequestration and metabolism of red cells. Indirect evidence suggested that the reticuloendothelial system is important in this process. To test this hypothesis, conversion of heme to bilirubin was studied in macrophages obtained by chemical or immunological means from the peritoneal cavity or from the lungs of rodents. Homogenates of pure populations of these cells were devoid of heme-oxygenase activity, unless before harvesting the macrophages had been exposed to methemalbumin, microcrystalline hemin, or hemoglobin in vivo. In macrophages exposed to heme pigments, the specific activity of heme-oxygenase was far in excess of that in the spleen or liver. Enzyme activity was also present in the granulomatous tissue surrounding subcutaneous hematomas. The heme-oxygenase system in macrophages resembles that in the spleen and liver in that it is localized in the microsomal fraction, has an absolute requirement for molecular oxygen and NADPH, is inhibited by carbon monoxide, and has a similar K(m). These findings indicate that cells of the reticuloendothelial system, presumably including the Kupffer cells of the liver and the macrophages of the spleen, possess the enzymatic machinery for converting hemoglobin-heme to bilirubin. The reaction is a mixed function oxidation, probably involving cytochrome P450 as the terminal oxidase. Enzyme activity in macrophages is capable of regulatory adaptation in response to substrate loads. In the standard assay system for the enzyme, disappearance of heme always was in excess of the amount of bilirubin formed, suggesting the simultaneous presence of alternate routes of heme degradation not involving bilirubin as an end product or intermediate.
TL;DR: In this paper, a quantitative estimation of the darkening effect of tetracyclines on permanent incisors was made by correlating tooth colors with the recorded history of TTI exposure in 160 children under care since infancy.
Abstract: A quantitative estimation of the darkening effect of tetracyclines on permanent incisors was made by correlating tooth colors with the recorded history of tetracycline exposure in 160 children under our care since infancy. The average darkening caused by one 6-day course of oral tetracycline or demethylchlortetracycline during the years of permanent incisor formation was 0.3 of a shade on a 14 shade dental scale. Children with five such courses of tetracycline therapy during the first 4½ to 5 years of life had permanent incisors averaging about two shades darker than children with no tetracycline exposure, a nearly imperceptible and cosmetically negligible difference; however, 3 of these 14 children had moderately darkened teeth. With greater frequency of tetracycline exposure, the risk increases; four of our six patients with eight or more courses had noticeably dark teeth. After age 6 for girls and 7 for boys the risk of tetracycline staining can be ignored since the cosmetically important anterior teeth have all formed. When tetracycline therapy is indicated during the first 6 to 7 years, the use of oxytetracycline (or possibly doxycycline) may diminish tooth darkening.
TL;DR: Results indicate that glucagon was cleaved by trypsin along functional lines into two parts, one of which housed the major antigenic determinant and the other of which carried the major immunogenic determinant, and they are highly compatible with a two-cell mechanism of immune induction.
Abstract: Bovine glucagon, a polypeptide of 29 amino acids, was immunogenic in guinea pigs. The immunologic determinants of glucagon were investigated using isolated tryptic peptides of the hormone. Antibodies from virtually all of more than two dozen animals had specificity primarily for the amino-terminal heptadecapeptide (NM) and showed little or no binding with the carboxy-terminal undeca- and dodecapeptides (C). The smallest synthetic peptide of a series initiated at residue 16 which measurably bound antibody comprised residues 5-16 of glucagon. In cellular immune assays, both NM and C elicited delayed cutaneous reactions and inhibited the migration of peritoneal cells from immune animals. However, only intact glucagon and its C fragment stimulated lymphoid cells to synthesize DNA. While glucagon was somewhat more active than C, the addition of NM to C did not enhance its transforming activity. The smallest synthetic carboxy-terminal peptide with discernible transforming activity comprised residues 19-29 of glucagon. In both native and synthetic C peptide preparations, the undecapeptide was generally more active than the dodecapeptide, although cells from different animals gave different response patterns. The difference between the two is the presence of arginine at the amino-terminus of the peptide chain. Thus, the recognition specificity of populations of antigen-reactive cells from different animals displays a variation which is at least superficially analogous to that of populations of antibody molecules. In limited experiments using NM and C peptides as immunogens, neither gave rise to delayed hypersensitivity or to glucagon-binding circulating antibody, following a regimen which invariably provoked these responses when glucagon itself served as the immunogen. These results indicate that glucagon was cleaved by trypsin along functional lines into two parts, one of which housed the major antigenic determinant and the other of which carried the major immunogenic determinant, and they are highly compatible with a two-cell mechanism of immune induction. An apparent dissociation between the capacity to provoke delayed hypersensitivity reactions and to transform antigen-reactive cells in culture was observed.
TL;DR: The detection of pyruvate kinase (PyK) activity after electrophoresis on cellulose polyacetate strips is presented, which is sensitive and selective and has the advantage of producing a permanent photographic record.
TL;DR: Step-by-step discussion of clinical procedures specifically designed for the anatomic and physiologic alterations of mandibulectomy patients discussed in terms of functional adaptability to surgical insult are presented.
Abstract: Part I of this series of articles dealing with the prosthetic treatment of mandibulectomy patients presents some general physiologic considerations pertinent to mandibulectomy patients discussed in terms of functional adaptability to surgical insult. Deglutition, speech, mandibular movement and mastication, saliva control, respiration, and psychosocial factors are characterized. A classification of mandibulectomy patients is suggested, and the anatomic and physiologic oral conditions of the patients in each group are described. Part II will present a step-by-step discussion of clinical procedures specifically designed for the anatomic and physiologic alterations of these patients. Part III will present an evaluation of these suggested procedures by means of a clinical research study of 30 mandibulectomy patients.