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Showing papers by "University of California, San Francisco published in 1988"


Journal ArticleDOI
TL;DR: The efficacy of this cDNA cloning strategy was demonstrated by isolating cDNA clones of mRNA from int-2, a mouse gene that expresses four different transcripts at low abundance, the longest of which is approximately 2.9 kilobases.
Abstract: We have devised a simple and efficient cDNA cloning strategy that overcomes many of the difficulties encountered in obtaining full-length cDNA clones of low-abundance mRNAs. In essence, cDNAs are generated by using the DNA polymerase chain reaction technique to amplify copies of the region between a single point in the transcript and the 3' or 5' end. The minimum information required for this amplification is a single short stretch of sequence within the mRNA to be cloned. Since the cDNAs can be produced in one day, examined by Southern blotting the next, and readily cloned, large numbers of full-length cDNA clones of rare transcripts can be rapidly produced. Moreover, separation of amplified cDNAs by gel electrophoresis allows precise selection by size prior to cloning and thus facilitates the isolation of cDNAs representing variant mRNAs, such as those produced by alternative splicing or by the use of alternative promoters. The efficacy of this method was demonstrated by isolating cDNA clones of mRNA from int-2, a mouse gene that expresses four different transcripts at low abundance, the longest of which is approximately 2.9 kilobases. After less than 0.05% of the cDNAs produced had been screened, 29 independent int-2 clones were isolated. Sequence analysis demonstrated that the 3' and 5' ends of all four int-2 mRNAs were accurately represented by these clones.

4,673 citations


Journal ArticleDOI
29 Apr 1988-Science
TL;DR: Apolipoprotein E is a plasma protein that serves as a ligand for low density lipoprotein receptors and, through its interaction with these receptors, participates in the transport of cholesterol and other lipids among various cells of the body.
Abstract: Apolipoprotein E is a plasma protein that serves as a ligand for low density lipoprotein receptors and, through its interaction with these receptors, participates in the transport of cholesterol and other lipids among various cells of the body A mutant form of apolipoprotein E that is defective in binding to low density lipoprotein receptors is associated with familial type III hyperlipoproteinemia, a genetic disorder characterized by elevated plasma cholesterol levels and accelerated coronary artery disease Apolipoprotein E is synthesized in various organs, including liver, brain, spleen, and kidney, and is present in high concentrations in interstitial fluid, where it appears to participate in cholesterol redistribution from cells with excess cholesterol to those requiring cholesterol Apolipo-protein E also appears to be involved in the repair response to tissue injury; for example, markedly increased amounts of apolipoprotein E are found at sites of peripheral nerve injury and regeneration Other functions of apolipoprotein E, unrelated to lipid transport, are becoming known, including immunoregulation and modulation of cell growth and differentiation

3,967 citations


Journal ArticleDOI
03 Jun 1988-Science
TL;DR: Fos immunohistochemistry provides a cellular method to label polysynaptically activated neurons and thereby map functional pathways in response to polysynaptic activation.
Abstract: The proto-oncogene c-fos is expressed in neurons in response to direct stimulation by growth factors and neurotransmitters. In order to determine whether the c-fos protein (Fos) and Fos-related proteins can be induced in response to polysynaptic activation, rat hindlimb motor/sensory cortex was stimulated electrically and Fos expression examined immunohistochemically. Three hours after the onset of stimulation, focal nuclear Fos staining was seen in motor and sensory thalamus, pontine nuclei, globus pallidus, and cerebellum. Moreover, 24-hour water deprivation resulted in Fos expression in paraventricular and supraoptic nuclei. Fos immunohistochemistry therefore provides a cellular method to label polysynaptically activated neurons and thereby map functional pathways.

1,962 citations


Journal ArticleDOI
TL;DR: The present research addresses this imbalance by evaluating the extent to which coping mediated emotions during stressful encounters in two Caucasian, community-residing samples by evaluating eight forms of coping mediated each of four sets of emotions.
Abstract: There is widespread conviction among health care professionals that coping affects emotion. Yet theory and research have traditionally emphasized the effects of emotion on coping. The present research addresses this imbalance by evaluating the extent to which coping mediated emotions during stressful encounters in two Caucasian, community-residing samples. Subjects' recently experienced stressful encounters, the ways they coped with the demands of those encounters, and the emotions they experienced during two stages of those encounters were assessed repeatedly. The extent to which eight forms of coping mediated each of four sets of emotions was evaluated with a series of hierarchical regression analyses (of residuals). Coping was associated with changes in all four sets of emotions, with some forms of coping associated with increases in positive emotions and other forms associated with increases in negative emotions.

1,766 citations


Journal ArticleDOI
TL;DR: Especially noteworthy among several differences in risk factor levels by demographic subgroup, were a higher body mass index among black than white women and much higher prevalence of cigarette smoking among persons with no more than a high school education than among those with more education.

1,486 citations


Journal ArticleDOI
TL;DR: Five groups of steroid hormones are generally recognized according to their physiological behavior: mineralocorticoids, which instruct the renal tubules to retain sodium; glucocortics, which are named for their carbohydratemobilizing properties but have many other effects as well; estrogens, which induce female secondary sexual characteristics; progestins, which is essential for reproduction; and androgens, who induce male secondarySexual characteristics.
Abstract: Introduction STEROID hormones are familiar clinically and physiologically as regulators of physiological processes. Five groups of steroid hormones are generally recognized according to their physiological behavior: mineralocorticoids, which instruct the renal tubules to retain sodium; glucocorticoids, which are named for their carbohydratemobilizing properties but have many other effects as well; estrogens, which induce female secondary sexual characteristics; progestins, which are essential for reproduction; and androgens, which induce male secondary sexual characteristics. These classes of steroid hormones are structurally similar and arise from a common series of pathways. They are distinguished by their actions on one or more specific steroid hormone receptors. The hormone/receptor complexes function as tissue-specific transcriptional regulators of distinct domains of genes and, consequently, exert their broad array of physiological effects. (For reviews, see Refs. 1 and 2.) The pathways by which the...

1,340 citations


Journal ArticleDOI
TL;DR: By selective changes in lipid composition, up to a 60-fold increase in the fraction of recovered dose present in blood 24 hr after i.v. injection is achieved, which has considerable therapeutic potential in cancer for increasing the concentration of cytotoxic agents in tumors while minimizing the likelihood of toxicity to the reticuloendothelial system.
Abstract: The rapid clearance of circulating liposomes from the bloodstream, coupled with their high uptake by liver and spleen, has thus far been an obstacle to any attempts at targeting to tumors. We have assessed the impact of liposome composition on their clearance from the circulation in normal and tumor-bearing mice and on their uptake by tumors and various normal tissues. By selective changes in lipid composition, while maintaining a mean particle diameter of approximately equal to 100 nm, we have achieved up to a 60-fold increase in the fraction of recovered dose present in blood 24 hr after i.v. injection. Concomitantly, there was a decrease by a factor of 4 of the recovered dose localizing in the liver and spleen, the major organs of the reticuloendothelial system. Parallel experiments in tumor-bearing mice demonstrated a 25-fold increase of the liposome concentration in the tumor when formulations with long and short blood residence time were compared. The most favorable results were obtained with liposomes containing a small molar fraction of a negatively charged glycolipid, such as monosialoganglioside or phosphatidylinositol, and a solid-phase neutral phospholipid as the bulk component. The bio-distribution of such formulations is of considerable therapeutic potential in cancer for increasing the concentration of cytotoxic agents in tumors while minimizing the likelihood of toxicity to the reticuloendothelial system.

1,187 citations


Journal ArticleDOI
05 Aug 1988-Science
TL;DR: Macrophages isolated from a wound site, and not exposed to cell culture conditions, expressed messenger RNA transcripts for TGF-alpha, T GF-beta, platelet-derived growth factor A-chain, and insulin-like growth factor-1 by a novel method for RNA analysis.
Abstract: The presence of macrophages is required for the regeneration of many cell types during wound healing. Macrophages have been reported to express a wide range of mitogenic factors and cytokines, but none of these factors has been shown in vivo to sustain all the wound-healing processes. It has been suggested that transforming growth factor-alpha (TGF-alpha) may mediate angiogenesis, epidermal regrowth, and formation of granulation tissue in vivo. Macrophages isolated from a wound site, and not exposed to cell culture conditions, expressed messenger RNA transcripts for TGF-alpha, TGF-beta, platelet-derived growth factor A-chain, and insulin-like growth factor-1. The expression of these transcripts was determined by a novel method for RNA analysis in which low numbers of mouse macrophages were isolated from wound cylinders, their RNA was purified and reverse-transcribed, and the complementary DNA was amplified in a polymerase chain reaction primed with growth factor sequence-specific primers. This single-cell RNA phenotyping procedure is rapid and has the potential for quantification, and mRNA transcripts from a single cell or a few cells can be unambiguously demonstrated, with the simultaneous analysis of several mRNA species. Macrophages from wounds expressed TGF-alpha antigen, and wound fluids contained TGF-alpha. Elicited macrophages in culture also expressed TGF-alpha transcripts and polypeptide in a time-dependent manner after stimulation with modified low-density lipoproteins and lipopolysaccharide endotoxin, which are characteristic of the activators found in injured tissues.

1,136 citations


Journal ArticleDOI
01 Apr 1988-Blood
TL;DR: The author’s website is www.hematologylibrary.org, which can be found online at http://bloodjournal.org/site/misc/rights.xhtml.

1,098 citations


Journal ArticleDOI
21 Jan 1988-Nature
TL;DR: It is reported that translation of HIV-1 RNA synthesized in vitro by SP6 RNA polymerase yields significant amounts of a gag-pol fusion protein, indicating that efficient ribosomal frameshifting also occurs within the HIV--pol overlap region.
Abstract: Based on precedents from other retroviruses, the precursor of the human immunodeficiency virus (HIV-1) reverse transcriptase is predicted to be a polyprotein with a relative molecular mass (Mr) of 160,000 (160K) encoded by both the viral pol gene and the upstream gag gene. These two genes lie in different translational reading frames, with the 3' end of gag overlapping the 5' end of pol by 205 or 241 nucleotides. Thus, production of the gag-pol fusion protein would require either messenger RNA processing or translational frameshifting. The latter mechanism has been shown in the synthesis of the gag-pol proteins of two other retroviruses, Rous sarcoma virus (RSV) and mouse mammary tumour virus (MMTV). Here we report that translation of HIV-1 RNA synthesized in vitro by SP6 RNA polymerase yields significant amounts of a gag-pol fusion protein, indicating that efficient ribosomal frameshifting also occurs within the HIV-1 gag-pol overlap region. Site-directed mutagenesis and amino-acid sequencing localized the site of frameshifting to a UUA leucine codon near the 5' end of the overlap.

969 citations


Journal ArticleDOI
TL;DR: At the core of MIDAS is a hierarchical database system, designed specifically for macromolecules, that is both compact in its storage requirements and fast in its data access.

Journal ArticleDOI
TL;DR: A striking evolutionary pattern in the expression of alpha-galactosyl epitopes on mammalian nucleated cells is observed, and an anomalous activity of this enzyme in man may result in initiation of autoimmune diseases because of the de novo expression of Gal alpha 1----3Gal beta 1----4GlcNAc-R epitopes recognized by anti-Gal.

Journal ArticleDOI
10 Jun 1988-Science
TL;DR: In Caenorhabditis elegans patterns of cell division, differentiation, and morphogenesis can be observed with single-cell resolution in intact, living animals.
Abstract: In Caenorhabditis elegans patterns of cell division, differentiation, and morphogenesis can be observed with single-cell resolution in intact, living animals. Mechanisms that determine behaviors of individual cells during development are being dissected by means of genetic, cell biological, and molecular approaches.

Journal ArticleDOI
TL;DR: The role of the epithelial adhesion molecule uvomorulin seems to mediate an early adhesion event between epithelial cells that is a prerequisite for the assembly of all elements of the junctional complex.
Abstract: The role of the epithelial adhesion molecule uvomorulin in the formation of the epithelial junctional complex in the Madin-Darby canine kidney (MDCK) cell line was investigated. Experiments were carried out to determine whether specific inhibition of uvomorulin function would interfere selectively with the formation, stability, or function of the apical zonula adherens (ZA) and zonula occludens (ZO), or whether it would interfere with all forms of intercellular contact including the desmosomes. The effects of blocking antibodies and Fab fragments to uvomorulin on the formation of the junctional complex was examined with a Ca2+ switch assay for de novo junction assembly. The formation of the ZO, the ZA, and the desmosomes was assayed by fluorescence staining with an antibody to the tight junction-specific protein ZO-1, with rhodamine-phalloidin for ZA-associated actin filaments, and with an anti-desmoplakin antibody, respectively. Under different conditions and times of antibody treatment the extent of inhibition of the formation of each of the junctional elements was very similar. The ability of the cells to eventually overcome the inhibitory effect of the antibodies and form junctions correlated with the reappearance of uvomorulin at the regions of cell-cell contact. Therefore uvomorulin seems to mediate an early adhesion event between epithelial cells that is a prerequisite for the assembly of all elements of the junctional complex. In contrast, the transepithelial electrical resistance of confluent, well-established monolayers of MDCK cells grown on filters was not greatly affected by treatment with the various antibodies or Fab fragments. A small transient decrease in resistance observed with the polyclonal alpha-uvomorulin IgG may be due to a more subtle modulation of the junctional complex.


Journal ArticleDOI
07 Oct 1988-Science
TL;DR: It is demonstrated that an increase in postsynaptic calcium is necessary to induce LTP and sufficient to potentiate synaptic transmission.
Abstract: Brief repetitive activation of excitatory synapses in the hippocampus leads to an increase in synaptic strength that lasts for many hours. This long-term potentiation (LTP) of synaptic transmission is the most compelling cellular model in the vertebrate brain for learning and memory. The critical role of postsynaptic calcium in triggering LTP has been directly examined using three types of experiment. First, nitr-5, a photolabile nitrobenzhydrol tetracarboxylate calcium chelator, which releases calcium in response to ultraviolet light, was used. Photolysis of nitr-5 injected into hippocampal CA1 pyramidal cells resulted in a large enhancement of synaptic transmission. Second, in agreement with previous results, buffering intracellular calcium at low concentrations blocked LTP. Third, depolarization of the postsynaptic membrane so that calcium entry is suppressed prevented LTP. Taken together, these results demonstrate that an increase in postsynaptic calcium is necessary to induce LTP and sufficient to potentiate synaptic transmission.

Journal ArticleDOI
TL;DR: It is concluded that elderly subjects often do not recall falls that occurred during specific periods of time over the preceding 3 to 12 months, and researchers and clinicians should consider using methods besides long‐term recall for ascertaining and counting falls over specific periods.
Abstract: To determine how accurately elderly subjects recall recent falls, we studied 304 ambulatory men and women over the age of 60 years who completed a 12-month prospective study of risk factors for falling. We developed a system of weekly follow-up and home visits to record and confirm all falls. During the study, 179 participants suffered at least one fall that was confirmed by home visit. At the end of the study, all subjects were interviewed by telephone about whether they had suffered a fall during the preceding 3, 6, or 12 months. Depending on the time period of recall, 13% to 32% of those with confirmed falls did not recall falling during the specific period of time. Recall was better for the preceding 12 months than for 3 or 6 months. There were only weak correlations (r = 0.28 to 0.59) between the number of falls that were documented and the number that the subjects recalled during each of these periods. Those with lower scores on the Mini-Mental State Examination were more likely to forget falls. We conclude that elderly subjects often do not recall falls that occurred during specific periods of time over the preceding 3 to 12 months. Researchers and clinicians should consider using methods besides long-term recall for ascertaining and counting falls over specific periods of time.

Journal ArticleDOI
18 Nov 1988-Cell
TL;DR: Mammary and salivary adenocarcinomas occur in these animals at rates indicating that transcriptional activation of int-1 and associated hyperplasia are initiating events in multistep carcinogenesis.

Journal ArticleDOI
11 Aug 1988-Nature
TL;DR: Phylogenetic analysis of Pneumocystis 16S-like rRNA demonstrates it to be a member of the Fungi, revealing that the plant, animal and fungal lineages are distinct from the diverse spectrum of protozoan lineages.
Abstract: Pneumocystis carinii pneumonia is the most common opportunistic infection in AIDS, and accounts for significant morbidity and mortality in these and other immunocompromised patients. P. carinii is a eukaryotic microorganism of uncertain taxonomy that can infect numerous mammalian hosts. Developing from a small, unicellular 'trophozoite' into a 'cyst' containing eight 'sporozoites', its life cycle superficially resembles those seen both in the Protozoa and Fungi. Morphological and ultrastructural observations have lead some investigators to conclude that the organism is a protozoan, while others have felt that it more closely resembles a fungus. Phylogenetic relationships can be inferred from comparisons of macromolecular sequences. Small subunit ribosomal RNAs (16S-like rRNAs) are well-suited for this purpose because they have the same function in all organisms and contain sufficient information to estimate both close and distant evolutionary relationships. Phylogenetic frameworks based upon such comparisons reveal that the plant, animal and fungal lineages are distinct from the diverse spectrum of protozoan lineages. In this letter, phylogenetic analysis of Pneumocystis 16S-like rRNA demonstrates it to be a member of the Fungi.

Journal ArticleDOI
01 Apr 1988-Science
TL;DR: The development of disease was found to be correlated with the emergence of HIV-1 variants that were more cytopathic in vitro as the disease progressed and that replicated more efficiently in a wide variety of different human cells.
Abstract: Individuals infected with the human immunodeficiency virus type 1 (HIV-1) may be asymptomatic or have AIDS-related complex or the acquired immuno deficiency syndrome (AIDS). Little is known about the factors that influence progression of infection to AIDS. In this study of isolates of HIV-1 obtained at intervals during the infection of four individuals, the development of disease was found to be correlated with the emergence of HIV-1 variants that were more cytopathic in vitro as the disease progressed and that replicated more efficiently in a wide variety of different human cells. The biologic properties of HIV-1 in vitro thus appear to reflect its virulence in the host. Further studies of such sequentially isolated viruses may lead to the identification of viral genes that govern pathogenesis.

Journal ArticleDOI
04 Aug 1988-Nature
TL;DR: This work has investigated the ability of each subtype to regulate PI hydrolysis and adenylyl cyclase when expressed individually in a cell lacking endogenous mAChRs and results indicate that the different receptor subtypes are functionally specialized.
Abstract: Muscarinic acetylcholine receptors (mAChRs), like many other neurotransmitter and hormone receptors, transduce agonist signals by activating G proteins to regulate ion channel activity and the generation of second messengers via the phosphoinositide (PI) and adenylyl cyclase systems. Human mAChRs are a family of at least four gene products which have distinct primary structures, ligand-binding properties and patterns of tissue-specific expression. To examine the question of whether functional differences exist between multiple receptor subtypes, we have investigated the ability of each subtype to regulate PI hydrolysis and adenylyl cyclase when expressed individually in a cell lacking endogenous mAChRs. We show that the HM2 and HM3 mAChRs efficiently inhibit adenylyl cyclase activity but poorly activate PI hydrolysis. In contrast, the HM1 and HM4 mAChRs strongly activate PI hydrolysis, but do not inhibit adenylyl cyclase, and in fact can substantially elevate cAMP levels. Interestingly, the subtypes that we find to be functionally similar are also more similar in sequence. Our results indicate that the different receptor subtypes are functionally specialized.

Journal ArticleDOI
30 Sep 1988-Science
TL;DR: The expression of a subset of growth factors in mouse blastocysts suggests a role for these factors in the growth and differentiation of early mammalian embryos.
Abstract: Control of growth and differentiation during mammalian embryogenesis may be regulated by growth factors from embryonic or maternal sources. With the use of single-cell messenger RNA phenotyping, the simultaneous expression of growth factor transcripts in single or small numbers of preimplantation mouse embryos was examined. Transcripts for platelet-derived growth factor A chain (PDGF-A), transforming growth factor (TGF)-alpha, and TGF-beta 1, but not for four other growth factors, were found in whole blastocysts. TGF-alpha, TGF-beta 1, and PDGF antigens were detected in blastocysts by immunocytochemistry. Both PDGF-A and TGF-alpha were detected as maternal transcripts in the unfertilized ovulated oocyte, and again in blastocysts. TGF-beta 1 transcripts appeared only after fertilization. The expression of a subset of growth factors in mouse blastocysts suggests a role for these factors in the growth and differentiation of early mammalian embryos.

Journal ArticleDOI
TL;DR: The data suggest that a significant part of cell-derived cholesterol is transferred specifically to a pre-beta-migrating lipoprotein A-I species as part of a cholesterol transport transfer sequence in plasma.
Abstract: Cultures of human skin fibroblasts were labeled to high cholesterol specific activity with [3H]cholesterol and incubated briefly (1-3 min) with normal human plasma. The plasma was fractionated by two-dimensional agarose-polyacrylamide gel electrophoresis and the early appearance of cholesterol label among plasma lipoproteins determined. A major part of the label at 1-min incubation was in a pre-beta-migrating apo A-I lipoprotein fraction with a molecular weight of ca. 70,000. Label was enriched about 30-fold in this fraction relative to its content of apo A-I (1-2% of total apo A-I). The proportion of label in this lipoprotein was strongly correlated with its concentration in plasma. Further incubation (2 min) in the presence of unlabeled cells demonstrated transfer of label from this fraction to a higher molecular weight pre-beta apo A-I species, to low-density lipoprotein, and to the alpha-migrating apo A-I that made up the bulk (96%) of total apo A-I in plasma. The data suggest that a significant part of cell-derived cholesterol is transferred specifically to a pre-beta-migrating lipoprotein A-I species as part of a cholesterol transport transfer sequence in plasma.

Journal ArticleDOI
01 May 1988-Neuron
TL;DR: The magnitude and displacement dependence of the gating compliance provide quantitative information about the molecular basis of mechanoelectrical transduction: the force required to open each channel, the number of transduction channels per hair cell, the stiffness of a gating spring, and the swing of a channel's gate as it opens.

Journal ArticleDOI
10 Mar 1988-Nature
TL;DR: Using the hippocampal slice preparation, the phosphonic acid derivative of baclofen is reported to be a remarkably selective antagonist of both the postsynaptic action of bclofen and the bicuculline-resistant action of GABA, and that it selectively abolishes the slow inhibitory post Synaptic potential in pyramidal cells.
Abstract: The role of GABA in synaptic transmission in the mammalian central nervous system is more firmly established than for any other neurotransmitter. With virtually every neuron studied, the synaptic action of GABA is mediated by bicuculline-sensitive GABAA receptors which selectively increase chloride conductance. However, it has been shown that GABA has a presynaptic inhibitory action on transmitter release that is insensiive to bicuculline and is selectively mimicked by baclofen. The receptors involved in this action are referred to as GABAB receptors, to distinguish them from the classic bicuculline-sensitive GABAA receptors. In hippocampal pyramidal cells an additional postsynaptic action of GABA and baclofen has been reported that is also insensitive to GABAA antagonists, and may be mediated by GABAB receptors on the postsynaptic neuron. This action of GABA and baclofen involves an increase in potassium conductance. Synaptic activation of pathways converging on hippocampal pyramidal cells results in a slow inhibitory postsynaptic potential which involves an increase in potassium conductance, and it has been suggested that GABAB receptors might be responsible for this synaptic potential. However, to establish convincingly that GABAB receptors are physiologically important in the central nervous system, a selective GABAB antagonist is required. Here we provide this missing evidence. Using the hippocampal slice preparation, we now report that the phosphonic acid derivative of baclofen, phaclofen, is a remarkably selective antagonist of both the postsynaptic action of baclofen and the bicuculline-resistant action of GABA, and that it selectively abolishes the slow inhibitory postsynaptic potential in pyramidal cells.

Journal ArticleDOI
18 Nov 1988-Cell
TL;DR: This gene turns out to be vasa, which is required maternally for the formation of polar granules and germ cells, and shows significant sequence similarity to eIF-4A, a translation initiation factor that binds to mRNA, and to other helicases.

Journal ArticleDOI
04 Nov 1988-Cell
TL;DR: A short sequence of RSV RNA, 147 nucleotides in length, containing the frameshift site and stem-loop structure, is sufficient to direct frameshifting in a novel genetic context.

Journal ArticleDOI
29 Jul 1988-Science
TL;DR: The existence of both convergence and divergence in the action of neurotransmitters results in a remarkable diversity in neuronal signaling.
Abstract: Recent studies on the action of neurotransmitters on hippocampal pyramidal cells indicate that different neurotransmitter receptors that use either the same or different coupling mechanisms converge onto the same ion channel. Conversely, virtually all of the neurotransmitters act on at least two distinct receptor subtypes coupled to different ion channels on the same cell. The existence of both convergence and divergence in the action of neurotransmitters results in a remarkable diversity in neuronal signaling.

Journal ArticleDOI
TL;DR: Overall nicotine exposure was twice as large after single exposures to smokeless tobacco compared with cigarette smoking, and relatively low levels of nicotine and lesser cardiovascular responses were observed with use of nicotine gum.
Abstract: Because of recent resurgence in its consumption, the effects and health consequences of smokeless tobacco are of considerable public health interest. We studied the extent and time course of absorption of nicotine and cardiovascular effects of smokeless tobacco (oral snuff and chewing tobacco) and compared it with smoking cigarettes and chewing nicotine gum in 10 healthy volunteers. Maximum levels of nicotine were similar but, because of prolonged absorption, overall nicotine exposure was twice as large after single exposures to smokeless tobacco compared with cigarette smoking. All tobacco use increased heart rate and blood pressure, with a tendency toward a greater overall cardiovascular effect despite evidence of development of some tolerance to effects of nicotine with use of smokeless tobacco. Relatively low levels of nicotine and lesser cardiovascular responses were observed with use of nicotine gum. Adverse health consequences of smoking that are nicotine related would be expected to present a similar hazard with the use of smokeless tobacco.

Journal ArticleDOI
TL;DR: Etude a 25°C de polymeres reticules a base de methacrylates de n-alkyle and de (dimethyl-amino) ethylmethacrylate Gonflement dans l'eau Transition de l'etat hydrophobe a l"etat hyphile Influence de la composition du comonomere
Abstract: Etude a 25°C de polymeres reticules a base de methacrylates de n-alkyle et de (dimethyl-amino) ethylmethacrylate Gonflement dans l'eau Transition de l'etat hydrophobe a l'etat hydrophile Influence de la composition du comonomere