Showing papers by "Tufts University published in 1991"
TL;DR: The protein-tyrosine kinase oncogenes will be the primary focus of the review as discussed by the authors, however, biochemical connections between the protein tyrosine Kinases and oncoproteins of the Ras,Raf,Fos,Jun, and Rel families as well as the protein kinase C family are also discussed.
2,686 citations
TL;DR: The recent cloning of a naturally occurring IL-1 receptor antagonist (IL-1ra) has opened new experimental and clinical approaches and reduced the severity of diseases such as hemodynamic shock, lethal sepsis, inflammatory bowel disease, experimental arthritis, and the spontaneous proliferation of human leukemic cells.
2,307 citations
TL;DR: Race-specific and population-based 85th and 95th percentiles of BMI and TSF for people aged 6-74 y were generated from anthropometric data gathered in the National Health and Nutrition Examination Survey Survey 1 (NHANES I).
1,382 citations
TL;DR: The c-abl proto-oncogene, which encodes a cytoplasmic protein-tyrosine kinase, is expressed throughout murine gestation and ubiquitously in adult mouse tissues, however, its levels are highest in thymus, spleen, and testes.
1,305 citations
TL;DR: Striking homology with the calcitonin receptor and lack of homological with other G protein-linked receptors indicate that receptors for these calcium-regulating hormones are related and represent a new family.
Abstract: The complementary DNA encoding a 585-amino acid parathyroid hormone-parathyroid hormone-related peptide (PTH-PTHrP) receptor with seven potential membrane-spanning domains was cloned by COS-7 expression using an opossum kidney cell complementary DNA (cDNA) library. The expressed receptor binds PTH and PTHrP with equal affinity, and both ligands equivalently stimulate adenylate cyclase. Striking homology with the calcitonin receptor and lack of homology with other G protein-linked receptors indicate that receptors for these calcium-regulating hormones are related and represent a new family.
1,222 citations
TL;DR: In children with acute Kawasaki disease, a single large dose of intravenous gamma globulin is more effective than the conventional regimen of four smaller daily doses and is equally safe.
Abstract: Background. Treatment of acute Kawasaki syndrome with a four-day course of intravenous gamma globulin, together with aspirin, has been demonstrated to be safe and effective in preventing coronary-artery lesions and reducing systemic inflammation. We hypothesized that therapy with a single, very high dose of gamma globulin would be at least as effective as the standard regimen. Methods. We conducted a multicenter, randomized, controlled trial involving 549 children with acute Kawasaki syndrome. The children were assigned to receive gamma globulin either as a single infusion of 2 g per kilogram of body weight over 10 hours or as daily infusions of 400 mg per kilogram for four consecutive days. Both treatment groups received aspirin (100 mg per kilogram per day through the 14th day of illness, then 3 to 5 mg per kilogram per day). Results. The relative prevalence of coronary abnormalities, adjusted for age and sex, among patients treated with the four-day regimen, as compared with those treated with...
1,054 citations
TL;DR: The estrogenic properties of alkylphenols, specifically nonylphenol, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkyLphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.
Abstract: Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. Th...
1,043 citations
TL;DR: Data suggest that MM is a major determinant of the age- and gender-related differences in skeletal muscle strength, independent of muscle location (upper vs. lower extremities) and function (extension vs. flexion).
Abstract: The isokinetic strength of the elbow and knee extensors and flexors was measured in 200 healthy 45- to 78-yr-old men and women to examine the relationship between muscle strength, age, and body com...
1,029 citations
TL;DR: Inositol 1,4,5 trisphosphate (IP3)-induced calcium release from intracellular stores is a regulator of cytosolic-free calcium levels as discussed by the authors.
Abstract: Inositol 1,4,5-trisphosphate (IP3)-induced calcium release from intracellular stores is a regulator of cytosolic-free calcium levels. The subsecond kinetics and regulation of IP3-induced calcium-45 release from synaptosome-derived microsomal vesicles were resolved by rapid superfusion. Extravesicular calcium acted as a coagonist, potentiating the transient IP3-induced release of calcium-45. Thus, rapid elevation of cytosolic calcium levels may trigger IP3-induced calcium release in vivo. Extravesicular calcium also produced a more slowly developing, reversible inhibition of IP3-induced calcium-45 release. Sequential positive and negative feedback regulation by calcium of IP3-induced calcium release may contribute to transients and oscillations of cytosolic-free calcium in vivo.
833 citations
TL;DR: The research and development costs of 93 randomly selected new chemical entities (NCEs) were obtained from a survey of 12 U.S.-owned pharmaceutical firms and used to estimate the pre-tax average cost of new drug development.
695 citations
TL;DR: In this paper, the authors estimate the strength of the electromagnetic fields produced due to the electroweak phase transition in the early universe and show that the resulting electromagnetic fields can also produce magnetic fields of other unbroken gauge symmetries such as SU(3)c.
Journal Article•
TL;DR: Although the differential tissue involvement in these infants with a fatal mitochondrial disease suggests mtDNA heteroplasmy, sequence analysis of mtDNA replication origins did not reveal any abnormality that could account for the low copy number.
Abstract: We studied two related infants with a fatal mitochondrial disease, affecting muscle in one and liver in the other. Quantitative analysis revealed a severe depletion of mtDNA in affected tissues. This genetic abnormality was also observed in muscle of an unrelated infant with myopathy and in muscle and kidney of a fourth child with myopathy and nephropathy. Biochemistry, immunohistochemistry, and in situ hybridization showed that the depletion of mtDNA in muscle fibers was correlated with a respiratory chain defect and with lack of mitochondrially translated proteins. Although the differential tissue involvement in these infants suggests mtDNA heteroplasmy, sequence analysis of mtDNA replication origins did not reveal any abnormality that could account for the low copy number.
TL;DR: A modified measure of human immunodeficiency virus-relevant items developed for the Medical Outcomes Study from subscales for cognitive function, energy/fatigue, health distress, and a single quality of life item were added to a portion of the MOS Short-form General Health Survey.
Abstract: Many current health status instruments either are too long to use in many acquired immune deficiency syndrome (AIDS) clinical trials or omit important concepts. In this study, human immunodeficiency virus (HIV)-relevant items developed for the Medical Outcomes Study (MOS) from subscales for cognitive function, energy/fatigue, health distress, and a single quality of life item were added to a portion of the MOS Short-form General Health Survey. The resulting 30-item questionnaire reliably and distinctly measured ten aspects of health and took less than 5 minutes to complete. To test its validity, this modified measure was used to compare the health of 73 subjects with asymptomatic HIV infection and 44 with early AIDS-related complex (ARC). Compared with ARC subjects, asymptomatic individuals reported superior overall health, less pain, and better physical function, role function, cognitive function, and quality of life (rank-sum, P less than 0.02). Asymptomatic subjects' scores were higher on most subscales than the age-adjusted scores of MOS outpatients with hypertension, diabetes, recent myocardial infarction, or depression; ARC patients scored closest to hypertensive patients. This instrument, containing a subset of the MOS measures of health-related quality of life, may be a useful outcome measure for AIDS clinical trials.
TL;DR: At latitude 42 degrees, healthy postmenopausal women with vitamin D intakes of 100 IU daily can significantly reduce late wintertime bone loss and improve net bone density of the spine over one year by increasing their intake of vitamin D to 500 IU daily.
Abstract: ▪Objectives:To determine whether relative vitamin D deficiency during the winter months contributes to age-related bone loss and whether rates of change in hard- and soft-tissue mass vary ...
TL;DR: It is concluded that specific blockade of IL 1 at the receptor level demonstrates an essential role for this cytokine in the pathogenesis of septic shock.
Abstract: Despite antibiotic therapy, the septic shock syndrome continues to have a high mortality. Tumor necrosis factor (TNF) and interleukin 1 (IL 1), two polypeptide cytokines produced during sepsis, are thought to mediate the hypotension and tissue damage of shock. In the present studies, rabbits were infused with Escherichia coli organisms to produce shock. The IL 1 receptor antagonist (IL 1ra), which competes with IL 1 for occupancy of the IL 1 cell-surface receptors without agonist properties, was given 15 min before the bacterial infusion and during the subsequent 4 h. In saline-treated controls, hypotension was sustained for 4 h and death occurred for two of five rabbits; in rabbits treated with the IL 1ra, however, blood pressure was only transiently decreased, returned to pre-E. coli levels, and no deaths occurred. The associated leukopenia was also reduced by treatment with the antagonist (P less than 0.05). Histological examination of lung tissues showed reduced infiltrating neutrophils in the IL 1ra ...
TL;DR: Use of neutralizing antibodies to TNF or to IL-1 receptors have reduced the consequences of infection and inflammation, including lethal outcomes in animal models.
Abstract: Treating the septic shock syndrome with antibodies that block only endotoxin has its limitations. Other targets for treating septic shock include neutralizing antibodies to the complement fragment C5a, platelet-activating factor antagonists, and blockade of endothelial cell leukocyte adhesion molecules. Specific blockade of the proinflammatory cytokines interleukin-1 (IL-1) or tumor necrosis factor (TNF) reduces the morbidity and mortality associated with septic shock. Moreover, blocking IL-1 and TNF likely has uses in treating diseases other than septic shock. Use of neutralizing antibodies to TNF or to IL-1 receptors have reduced the consequences of infection and inflammation, including lethal outcomes in animal models. The IL-1 receptor antagonist, a natural-occurring cytokine, blocks shock and death due to Escherichia coli and ameliorates a variety of inflammatory diseases. Soluble TNF and IL-1 surface receptors, which bind their respective cytokines, also ameliorate disease processes. Current clinical trials are evaluating the safety and efficacy of these anticytokine therapies either alone or together.
TL;DR: In this paper, the authors discuss how research in the developmental cognitive neurosciences can contribute to an understanding of the complex relations between various aspects of naming and reading processes and suggest the existence of a naming-rate deficit that differentiates dyslexic from average and garden-variety poor readers; this deficit appears to persist well into middle childhood.
Abstract: THIS TWO-PART ESSAY discusses how research in the developmental cognitive neurosciences can contribute to an understanding of the complex relations between various aspects of naming and reading processes. The first section reviews findings from both neuropsychological and reading research on letter-naming and general naming speed, and analyzes the methodological differences between discrete-trial and continuous naming formats. The findings taken together suggest that the relations between subprocesses change both with development and as the cognitive requirements for naming and reading tasks become more differentiated. Findings from a number of studies also suggest the existence of a naming-rate deficit that differentiates dyslexic from average and garden-variety poor readers; this deficit appears to persist well into middle childhood. The second section speculates more broadly about whether the relations between naming and reading deficits are causal or associative, and also about associations between deficits in naming speed and deficits in motoric speed. These associations could be explained by the existence of a connector variable common to some processes in both language and motoric domains, such as a hypothesized precise timing mechanism that may inhibit the ability of some dyslexic readers to achieve rapid processing.
TL;DR: Treatment modalities vary depending upon the nature of the complication, but for the most frequent complication, tracheal stenosis, a multidisciplinary approach utilizing bronchoscopy, laser, airway stents, andtracheal surgery is most effective.
Abstract: Tracheostomy may be associated with numerous acute, perioperative complications, some of which continue to be relevant well after the placement of the tracheostomy. A number of clinically important unique late complications have been recognized as well, including the formation of granulation tissue, tracheal stenosis, tracheomalacia, tracheoinnominate-artery fistula, tracheoesophageal fistula, ventilator-associated pneumonia, and aspiration. The clinical relevance of these complications is considerable, as their manifestations range from minimally symptomatic to failure to wean from the ventilator (tracheal stenosis) to life-threatening hemorrhage (tracheoinnominate fistula). Treatment modalities vary depending upon the nature of the complication. For the most frequent complication, tracheal stenosis, a multidisciplinary approach utilizing bronchoscopy, laser, airway stents, and tracheal surgery is most effective.
Harvard University1, Stanford University2, Tufts University3, Icos4, University of Washington5, Boehringer Ingelheim6, Genentech7, University of Oklahoma8, Cytel9, University of California, Berkeley10, University of Texas Southwestern Medical Center11, University of Michigan12, University of California, San Diego13, University of Utah14
TL;DR: This paper proposes that a group of cell surface proteins, originally studied independently as lymphocyte homing receptors or as activation-induced surface proteins of platelets and/or endothelial cells, are structurally related and should be named selectins to reflect the involvement of carbohydrate recognition in their functions.
TL;DR: The results suggest that the predominant natural response to endotoxin in man is the production of antagonist rather than agonist, which is a hundred-fold greater than those of IL-1 beta.
01 Jan 1991
TL;DR: The roles of hyaluronan (HA) and proteoglycans (PGs) in developmental processes and tissue remodeling are discussed and three developmental systems are chosen to illustrate ways in which HA or PGs are involved in actual morphogenetic and differentiative processes.
Abstract: The objective of this chapter is to discuss the roles of hyaluronan (HA) and proteoglycans (PGs) in developmental processes and tissue remodeling. In the first section I have summarized recent progress on the molecular basis of HA and PG interactions with the surface of cells, since this is the most likely means whereby HA and PGs would influence cell behavior during development. This is followed by a review of cellular studies, mainly performed in vitro, that implicate HA and PGs in specific aspects of cell behavior that would be relevant to development in vivo. Finally, I have chosen three developmental systems to illustrate ways in which HA or PGs are involved in actual morphogenetic and differentiative processes.
TL;DR: Analyses of model systems indicate that the particular mammalian cell receptors bound and the nature of the binding event dictate whether the bacterium remains extracellular or enters host cells.
Abstract: Most bacterial pathogens initiate infectious diseases by adhering to host cells. Bacterial adherence to nonphagocytic cells usually leads to extracellular colonization; however, many invasive microorganisms enter host cells after binding to the host cell surface. It is unclear why bacterial adherence can result in these two different fates for the microorganism. Analyses of model systems, such as the uptake of enteropathogenic Yersinia into cultured cells, indicate that the particular mammalian cell receptors bound and the nature of the binding event dictate whether the bacterium remains extracellular or enters host cells.
TL;DR: The first successful production of transgenic goats that express a heterologous protein in their milk was reported in this article, where the first animal, a female, was mated and allowed to carry the pregnancy to term.
Abstract: We report the first successful production of transgenic goats that express a heterologous protein in their milk. The production of a glycosylation variant of human tPA (LAtPA--longer acting tissue plasminogen activator) from an expression vector containing the murine whey acid promoter (WAP) operatively linked to the cDNA of a modified version of human tPA was examined in transgenic dairy goats. Two transgenic goats were identified from 29 animals born. The first animal, a female, was mated and allowed to carry the pregnancy to term. Milk was obtained upon parturition and was shown to contain enzymatically active LAtPA at a concentration of 3 micrograms/ml.
TL;DR: A general model is suggested in which mammary tumour virus gene products themselves are the ligands that shape a considerable portion of the immuno-logical repertoire of common laboratory mice.
Abstract: T CELLS that recognize self antigen are clonally deleted in the thymus—a maturation process that occurs in the context of histo-compatibility molecules and the T-cell receptor. The minor lymphocyte stimulation antigens (Mis) effect these deletions through interactions with the Vβ portion of the T-cell receptor, thus mimicking bacterial 'superantigens'. Intrigued by the fact that each known Mls gene maps to the same chromosomal region as an endogenous mouse mammary tumour virus (Mtv), we re-evaluated the linkage relationships between the two gene families. Here we report perfect concordance in inbred and recombinant inbred mice between the presence of four Mtv proviruses with the expression of Mls gene products. These data suggest a general model in which mammary tumour virus gene products themselves are the ligands that shape a considerable portion of the immuno-logical repertoire of common laboratory mice.
TL;DR: The results suggest that mast cells may secrete in response to electrical stimulation of trigeminal axons, possibly mediated by antidromic release of neuropeptides, and may participate in the development of neurogenic inflammation.
TL;DR: The T-cell proliferative assay may be a helpful diagnostic test in the small subset of patients with late Lyme disease who have negative or indeterminant antibody responses by ELISA.
Abstract: ▪Objective:To determine the sensitivity and specificity of the T-cell proliferative assay as a diagnostic test in Lyme disease. ▪Design:Cross-sectional study of patients with Lyme arthriti...
TL;DR: In two experiments, event-related brain potentials were collected as subjects listened to spoken sentences as mentioned in this paper, where all words were presented as connected (natural) speech and there was a 750msec interstimulus interval (ISI) separating each of the words.
Abstract: In two experiments, event-related brain potentials were collected as subjects listened to spoken sentences. In the first, all words were presented as connected (natural) speech. In the second, there was a 750-msec interstimulus interval (ISI) separating each of the words. Three types of senten-ending words were used: best completions (contextually meaningful), unrelated anomalies (contextually meaningless), and related anomalies (contextually meaningless but related to the best completion). In both experiments, large N400s were found for the unrelated and related anomalies, relative to those found for the best-completion final words, although the effect was earlier and more prolonged for unrelated anomalies. The auditory N400 effect onset earlier in the natural-speech experiment than it did in either the 750-msec ISI experiment or previous visual studies.
TL;DR: A shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli infusion, providing further evidence that host factors such as IL- 1 and T NF are common mediators of the septic shock syndrome regardless of the organism.
Abstract: Tumor necrosis factor (TNF) and IL-1 are thought to mediate many of the pathophysiologic changes of endotoxemia and Gram-negative bacteremia. In these studies, heat-killed Staphylococcus epidermidis were infused into rabbits to determine whether an endotoxin (LPS)-free microorganism also elicits cytokinemia and the physiologic abnormalities seen in Gram-negative bacteremia. S. epidermidis induced complement activation, circulating TNF and IL-1, and hypotension to the same degree as did one-twentieth the number of heat-killed Escherichia coli. Circulating IL-1 beta levels had a greater correlation coefficient (r = 0.81, P less than 0.001) with the degree of hypotension than TNF levels (r = 0.48, P less than 0.02). Leukopenia, thrombocytopenia, diffuse pulmonary capillary aggregation of neutrophils, and hepatic necrosis with neutrophil infiltration were observed to the same extent after either S. epidermidis or E. coli infusion. However, S. epidermidis infusion did not induce significant (less than 60 pg/ml) endotoxemia, whereas E. coli infusion resulted in high (11,000 pg/ml) serum endotoxin levels. S. epidermidis, E. coli, LPS, or S. epidermidis-derived lipoteichoic acid (LTA) induced TNF and IL-1 from blood mononuclear cells in vitro. E. coli organisms and LPS were at least 100-fold more potent than S. epidermidis or LTA. Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. These data provide further evidence that host factors such as IL-1 and TNF are common mediators of the septic shock syndrome regardless of the organism.
TL;DR: Two short-lived precursor proteins, pp37 and pp32, of the mitochondrial phosphoprotein pp30 have been detected in Bt2cAMP-stimulated rat adrenal cortex cells, incubated at 25 degrees C or with 1,10-ortho-phenanthroline at 37 degrees C, consistent with pp37 being a precursor protein that contains two cleavable presequences and is imported into the mitochondrion.
TL;DR: In this paper, a tensor transformation of the effective elastic constants for isotropic orientation statistics through the use of a second-order crack density tensor is presented, which is based on a tensorial transformation for estimating the elastic stiffness tensor.