Showing papers by "Tufts University published in 1988"
TL;DR: IL 1 is a highly inflammatory molecule and stimulates the production of arachidonic acid metabolites and acts synergistically with other cytokines, particularly tumor necrosis factor.
Abstract: Interleukin 1 (IL 1) is a polypeptide that is produced after infection, injury, or antigenic challenge. Although the macrophage is a primary source of IL 1, epidermal, epithelial, lymphoid, and vascular tissues synthesize IL 1. When IL 1 gains access to the circulation, it acts like a hormone and induces a broad spectrum of systemic changes in neurological, metabolic, hematologic, and endocrinologic systems. Some of the IL 1 that is synthesized remains associated with the plasma membrane and induces changes in local tissues without producing systemic responses. IL 1 affects mesenchymal tissue remodeling where it contributes to both destructive and repair processes. IL 1 activates lymphocytes and plays an important role in the initiation of the immune response. Receptors for IL 1 have been identified, but receptors are scarce and their affinities often do not match the potency of the biological response. The most consistent property of IL 1 is up-regulation of cellular metabolism and increased expression of several genes coding for biologically active molecules. IL 1 is a highly inflammatory molecule and stimulates the production of arachidonic acid metabolites. IL 1 also acts synergistically with other cytokines, particularly tumor necrosis factor. The multitude of biological responses to IL 1 is an example of the rapid adaptive changes that take place to increase the host's defensive mechanisms.
1,532 citations
TL;DR: This work focuses on the molecular basis of blood coagulation with particular attention to the biochemistry and regulation of this pathway as it relates to humans in health and disease.
1,298 citations
TL;DR: It is proposed that type I Ptdlns kinase is responsible for the generation of PtdIns(3)P in intact cells, and that this novel phosphoinositide could be important in the transduction of mitogenic and oncogenic signals.
Abstract: The generation of second messengers from the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdInsP2) by phosphoinositidase C has been implicated in the mediation of cellular responses to a variety of growth factors and oncogene products. The first step in the production of PtdInsP2 from phosphatidylinositol (PtdIns) is catalysed by PtdIns kinase. A PtdIns kinase activity has been found to associate specifically with several oncogene products, as well as with the platelet-derived growth factor (PDGF) receptor. We have previously identified two biochemically distinct PtdIns kinases in fibroblasts, and have found that only one of these, designated type I, specifically associates with activated tyrosine kinases. We have now characterized the site on the inositol ring phosphorylated by type I PtdIns kinase, and find that this kinase specifically phosphorylates the D-3 ring position to generate a novel phospholipid, phosphatidylinositol-3-phosphate (PtdIns(3)P). In contrast, the main PtdIns kinase in fibroblasts, designated type II, specifically phosphorylates the D-4 position to produce phosphatidylinositol-4-phosphate (PtdIns(4)P), previously considered to be the only form of PtdInsP. We have also tentatively identified PtdIns(3)P as a minor component of total PtdInsP in intact fibroblasts. We propose that type I PtdIns kinase is responsible for the generation of PtdIns(3)P in intact cells, and that this novel phosphoinositide could be important in the transduction of mitogenic and oncogenic signals.
986 citations
TL;DR: IL-1, like TNF, possesses the ability to induce hemodynamic and hematological changes typical of septic shock, and that the combination of IL-1 and TNF is more potent than either agent alone.
Abstract: In addition to activating T and B lymphocytes, interleukin 1 (IL-1) induces several hematologic and metabolic changes typical of host responses to infection and injury. We now report a new biological property, namely, the induction of hypotension. Rabbits given a single intravenous injection of recombinant human IL-1-beta (5 micrograms/kg) rapidly developed decreased systemic arterial pressure, which reached the lowest levels after 50-60 min and slowly returned to pre-IL-1 values after 3 h. Associated with the hypotension, systemic vascular resistance and central venous pressure fell, while cardiac output and heart rate increased. These responses were prevented by ibuprofen given 15 min before the IL-1. A bolus injection of IL-1 followed by a 2-h infusion sustained the hypotension and was associated with leukopenia and thrombocytopenia. Ibuprofen given at the mid-point of the infusion reversed the changes in all hemodynamic parameters, but had no effect on the leukopenia or thrombocytopenia. Tumor necrosis factor (TNF) also induced a shock-like state in rabbits. When the dose of IL-1 or TNF was reduced to 1 microgram/kg, no hemodynamic changes were observed; however, the combination of these low doses of both cytokines resulted in a profound shock-like state including histological evidence of severe pulmonary edema and hemorrhage. Pretreatment with ibuprofen prevented the hemodynamic, leukocyte, and platelet changes induced by the low-dose cytokine combination, and ameliorated the pulmonary tissue damage. These results demonstrate that IL-1, like TNF, possesses the ability to induce hemodynamic and hematological changes typical of septic shock, and that the combination of IL-1 and TNF is more potent than either agent alone. These effects seem to require cyclooxygenase products, and suggest that intravenous cyclooxygenase inhibitors may be of therapeutic value in patients with IL-1/TNF-mediated shock.
944 citations
TL;DR: The Asn-17 mutant represents a novel reagent for the study of ras function by virtue of its ability to inhibit cellular ras activity in vivo and is associated with the preferential affinity of the mutant protein for GDP.
Abstract: Substitution of asparagine for serine at position 17 decreased the affinity of rasH p21 for GTP 20- to 40-fold without significantly affecting its affinity for GDP. Transfection of NIH 3T3 cells with a mammalian expression vector containing the Asn-17 rasH gene and a Neor gene under the control of the same promoter yielded only a small fraction of the expected number of G418-resistant colonies, indicating that expression of Asn-17 p21 inhibited cell proliferation. The inhibitory effect of Asn-17 p21 required its localization to the plasma membrane and was reversed by coexpression of an activated ras gene, indicating that the mutant p21 blocked the endogenous ras function required for NIH 3T3 cell proliferation. NIH 3T3 cells transformed by v-mos and v-raf, but not v-src, were resistant to inhibition by Asn-17 p21, indicating that the requirement for normal ras function can be bypassed by these cytoplasmic oncogenes. The Asn-17 mutant represents a novel reagent for the study of ras function by virtue of its ability to inhibit cellular ras activity in vivo. Since this phenotype is likely associated with the preferential affinity of the mutant protein for GDP, analogous mutations might also yield inhibitors of other proteins whose activities are regulated by guanine nucleotide binding.
784 citations
TL;DR: Results indicate that IL-1 may be an intrinsic neuromodulator in central nervous system pathways that mediate various metabolic functions of the acute phase reaction, including the body temperature changes that produce the febrile response.
Abstract: Interleukin-1 (IL-1) is a cytokine that mediates the acute phase reaction. Many of the actions of IL-1 involve direct effects on the central nervous system. However, IL-1 has not previously been identified as an intrinsic component within the brain, except in glial cells. An antiserum directed against human IL-1 beta was used to stain the human brain immunohistochemically for IL-1 beta-like immunoreactive neural elements. IL-1 beta-immunoreactive fibers were found innervating the key endocrine and autonomic cell groups that control the central components of the acute phase reaction. These results indicate that IL-1 may be an intrinsic neuromodulator in central nervous system pathways that mediate various metabolic functions of the acute phase reaction, including the body temperature changes that produce the febrile response.
759 citations
TL;DR: In this article, a methodology for the valuation of claims on a real asset: an offshore petroleum lease is presented. And the authors show the necessity of combining option pricing techniques with a model of equilibrium in the market for the underlying asset (petroleum reserves), emphasizing the advantages of this approach over conventional discounted cash flow techniques.
Abstract: This paper extends financial option theory by developing a methodology for the valuation of claims on a real asset: an offshore petroleum lease. Several theoretical and practical problems, not present in applying option pricing theory to financial assets, are addressed. Most importantly, we show the necessity of combining option pricing techniques with a model of equilibrium in the market for the underlying asset (petroleum reserves). The advantages of this approach over conventional discounted cash flow techniques are emphasized. The methodological development provides important insights for both company behavior and government policy. Promising empirical results are reported.
687 citations
TL;DR: IL-1 produced by activated monocytes at sites of tissue inflammation or injury may mediate both positive and negative effects on SMC proliferation that are temporally distinct.
Abstract: There is much interest in defining the signals that initiate abnormal proliferation of cells in a variety of states characterized by the presence of mononuclear phagocytes. Since IL-1 is a major secretory product of activated human monocytes we examined whether this cytokine can stimulate the growth of human vascular smooth muscle cells (SMC). Neither recombinant IL-1 (rIL-1) alpha (less than or equal to 5.0 ng/ml) nor beta (less than or equal to 100 ng/ml) stimulated SMC growth during 2-d incubations under usual conditions. IL-1 did stimulate SMC to produce prostanoids such as PGE1 or PGE2 that can inhibit SMC proliferation. When prostaglandin synthesis was inhibited by indomethacin or aspirin both rIL-1 alpha and beta (greater than or equal to 1 ng/ml) markedly increased SMC growth. In longer-term experiments (7-28 d) rIL-1 stimulated the growth of SMC even in the absence of cyclooxygenase inhibitors. The addition of exogenous PGE1 or PGE2 (but not PGF1 alpha, PGF2 alpha, PGI2) to indomethacin-treated SMC blocked their mitogenic response to rIL-1. Antibody to IL-1 (but not to platelet-derived growth factor [PDGF]) abolished the mitogenic response of SMC to rIL-1. Exposure of SMC to rIL-1 or PDGF caused rapid (maximal at 1 h) and transient (baseline by 3 h) expression of the c-fos proto-oncogene, determined by Northern analysis. We conclude that IL-1 is a potent mitogen for human SMC. Endogenous prostanoid production simultaneously induced by IL-1 appears to antagonize this growth-promoting effect in the short term (2 d) but not during more prolonged exposures. IL-1 produced by activated monocytes at sites of tissue inflammation or injury may thus mediate both positive and negative effects on SMC proliferation that are temporally distinct.
509 citations
TL;DR: The results suggest that putative melatonin receptors are located in a human biological clock, and specifically found in the suprachiasmatic nuclei of hypothalami from adults and fetuses.
Abstract: In vitro autoradiography with 125I-labeled melatonin was used to examine melatonin binding sites in human hypothalamus. Specific 125I-labeled melatonin binding was localized to the suprachiasmatic nuclei, the site of a putative biological clock, and was not apparent in other hypothalamic regions. Specific 125I-labeled melatonin binding was consistently found in the suprachiasmatic nuclei of hypothalami from adults and fetuses. Densitometric analysis of competition experiments with varying concentrations of melatonin showed monophasic competition curves, with comparable half-maximal inhibition values for the suprachiasmatic nuclei of adults (150 picomolar) and fetuses (110 picomolar). Micromolar concentrations of the melatonin agonist 6-chloromelatonin completely inhibited specific 125I-labeled melatonin binding, whereas the same concentrations of serotonin and norepinephrine caused only a partial reduction in specific binding. The results suggest that putative melatonin receptors are located in a human biological clock.
503 citations
TL;DR: Changes in postprandial cholesterolemia was inversely correlated with fasting levels of HDL cholesterol levels, and positively correlated with age.
455 citations
TL;DR: Estimated tunneling rates of the magnetization in a single-domain particle through an energy barrier between easy directions prove to be large enough for observation of the effect with the use of existing experimental techniques.
Abstract: The probability of tunneling of the magnetization in a single-domain particle through an energy barrier between easy directions is calculated for several forms of magnetic anisotropy. Estimated tunneling rates prove to be large enough for observation of the effect with the use of existing experimental techniques.
TL;DR: The failure of coding joint formation in scid pre-B and pre-T cells appears sufficient to explain the absence of immunoglobulin or T cell receptor production inScid mice.
TL;DR: It is shown that IL-1 stimulates rapid diacylglycerol and phosphorylcholine production from phosphatidylcholine in the absence of phosph atidylinositol turnover in Jurkat cells, and this effect is also observed in peripheral blood T cells and a murine T cell line.
TL;DR: It is shown that the tunneling wave function predicts initial states that lead to inflation, while the Hartle-Hawking wave function does not.
Abstract: Cosmological wave functions are found in a minisuperspace model (1) with ``tunneling'' and (2) with Hartle-Hawking boundary conditions. The probability distributions for the initial states of the Universe corresponding to the two wave functions are calculated and compared. It is shown that the tunneling wave function predicts initial states that lead to inflation, while the Hartle-Hawking wave function does not. Small perturbations about the minisuperspace model are considered and it is argued that both wave functions predict that the Universe nucleates with quantum fields in de Sitter-invariant vacuum states.
TL;DR: Investigators trying to determine what triggers the hypothalamus to initiate fever in a particular disease must now consider these three endogenous pyrogens, either alone or together, as mediators of fever.
Abstract: For more than 50 years, experimental studies on fever have focused on a substance from leukocytes called leukocytic or endogenous pyrogen. Various investigators concluded that changes associated with infection--such as numbers of circulating leukocytes; levels of trace metals, amino acids, and hepatic proteins; and altered lymphocyte function--were also caused by endogenous leukocyte mediators. There was reasonable evidence that fever and these other changes were brought about through the action of a single endogenous pyrogen, now known as interleukin 1 (IL-1). Two forms of IL-1 have been cloned (IL-1 beta and IL-1 alpha), and studies of recombinant IL-1 preparations have confirmed that fever and the broad spectrum of host responses to infection and injury are indeed mediated by this substance. However, IL-1 is not the only leukocyte product that induces fever: tumor necrosis factor (cachectin) and interferon produce fever in humans and animals. Accordingly, the concept of a single endogenous pyrogen now requires modification. Nature has conferred the ability to produce fever on no fewer than three structurally distinct molecules. Investigators trying to determine what triggers the hypothalamus to initiate fever in a particular disease must now consider these three endogenous pyrogens, either alone or together, as mediators of fever.
TL;DR: A definition of nonantral gastric endocrine hyperplasia, dysplasia (enlarging or fusing micronodules, microinvasion, nodular growth) and neoplasia (intramucosal carcinoid, invasive carcinoid) is presented.
Abstract: Recently, the gastric endocrine system has been recognized as the origin of benign and malignant tumors in pernicious anemia. It has also been found that the gastric endocrine cells respond to permanent elevation of serum gastrin levels induced by changes in acid secretion in response to surgical procedures, drug therapy and age. Therefore, a definition of nonantral gastric endocrine hyperplasia (simple or diffuse, linear or chain-forming, micronodular, adenomatoid), dysplasia (enlarging or fusing micronodules, microinvasion, nodular growth) and neoplasia (intramucosal carcinoid, invasive carcinoid) is presented. The individual entities are illustrated, together with the literature discussed and the techniques for their identification presented.
TL;DR: It is concluded that smooth-muscle cells from diseased human arteries can secrete mitogenic activity, some of which resembles PDGF, and that these cells express the gene for the PDGF A chain selectively.
Abstract: Proliferation of vascular smooth-muscle cells occurs during the development of atherosclerosis and the remodeling of arteries that accompanies chronic systemic or pulmonary hypertension. To help define the signals that initiate this abnormal growth, we cultured smooth-muscle cells from human atherosclerotic plaques. These cells (n = 9) released material into their culture medium that stimulated the proliferation of aortic smooth-muscle cells to a mean (±SD) level 5.1±1 times that in control medium. Part of this activity was due to molecules that resemble a mitogen first isolated from platelets and known as platelet-derived growth factor (PDGF), since these cells released PDGF measured in a radioreceptor assay (355±117 pg per milliliter per 48 hours; n = 6) and since anti-PDGF antibody neutralized 38±7 percent of this mitogenic activity (range, 13 to 60 percent; n = 6 carotid-plaque isolates). Two human genes encode distinct PDGF subunits that form dimers in different combinations to create biolog...
TL;DR: Exoenzyme C3 from Clostridium botulinum types C and D specifically ADP-ribosylated a 21-kilodalton cellular protein, p21.bot, was immunologically distinct from p21ras, and caused temporary morphological alterations similar to those seen after microinjection of cloned ras proteins.
Abstract: Exoenzyme C3 from Clostridium botulinum types C and D specifically ADP-ribosylated a 21-kilodalton cellular protein, p21.bot. Guanyl nucleotides protected the substrate against denaturation, which implies that p21.bot is a G protein. When introduced into the interior of cells, purified exoenzyme C3 ADP-ribosylated intracellular p21.bot and changed its function. NIH 3T3, PC12, and other cells rapidly underwent temporary morphological alterations that were in certain respects similar to those seen after microinjection of cloned ras proteins. When injected into Xenopus oocytes, C3 induced migration of germinal vesicles and potentiated the cholera toxin-sensitive augmentation of germinal vesicle breakdown by progesterone, also as caused by ras proteins. Nevertheless, p21.bot was immunologically distinct from p21ras.
TL;DR: It is shown here that oriC DNA binds to membrane only when it is hemimethylated, and a speculative model for chromosome segregation in E. coli is proposed.
TL;DR: The findings suggest that the marA locus directly or indirectly increases micF expression, causing a posttranscriptional decrease in ompF mRNA and reduced amounts of OmpF.
Abstract: Mar (multiple antibiotic resistant) mutants of Escherichia coli express chromosomally mediated resistance to a variety of structurally unrelated hydrophilic and hydrophobic antibiotics. Insertion of transposon Tn5 into the marA locus at min 34.05 on the chromosome completely reverses the Mar phenotype (A. M. George and S. B. Levy, J. Bacteriol. 155:531-540, 1983). We found that among changes in the outer membrane of Mar mutants, porin OmpF was greatly reduced, although Mar mutants were more resistant than cells lacking only OmpF. Transduction of the marA region from a Mar strain, but not a wild-type strain, led to loss of OmpF. P1 transduction of marA::Tn5 into a Mar mutant partially restored OmpF levels. Therefore, OmpF reduction required a mutation in the marA region. Mar mutants of an ompF-lacZ operon fusion strain expressed 50 to 75% of the beta-galactosidase activity of the isogenic non-Mar parental strain, while Mar mutants of a protein fusion strain expressed less than 10% of the enzyme activity in the non-Mar strain. These changes were completely reversed by insertion of marA::Tn5. The responsiveness of OmpF-LacZ to osmolarity and temperature changes was similar in Mar and wild-type strains. Although some transcriptional control may have been present, OmpF reduction appeared to occur primarily by a posttranscriptional mechanism. The steady-state levels of ompF mRNA were twofold lower and the mRNA was five times less stable in the Mar mutant than in the wild-type strain. Expression of micF, which lowers ompF mRNA levels, was elevated in Mar strains, as revealed by a micF-lacZ fusion. Studies with strains deleted for the micF locus showed that the marA-dependent reduction of OmpF required an intact micF locus. Our findings suggest that the marA locus directly or indirectly increases micF expression, causing a posttranscriptional decrease in ompF mRNA and reduced amounts of OmpF.
TL;DR: Diallyl thiosulfinate (allicin) is the agent found in garlic which is responsible for the antibacterial and antifungal activity of extracts of this plant and inhibition of RNA synthesis was immediate and total, suggesting that this is the primary target of allicin action.
Abstract: Diallyl thiosulfinate (allicin) is the agent found in garlic which is responsible for the antibacterial and antifungal activity of extracts of this plant. The effect of bacteriostatic concentrations of allicin (0.2 to 0.5 mM) on the growth of Salmonella typhimurium revealed a pattern of inhibition characterized by: (i) a lag of approximately 15 min between addition of allicin and onset of inhibition, (ii) a transitory inhibition phase whose duration was proportional to allicin concentration and inversely proportional to culture density, (iii) a resumed growth phase which showed a lower rate of growth than in uninhibited controls, and (iv) an entry into stationary phase at a lower culture density. Whereas DNA and protein syntheses showed a delayed and partial inhibition by allicin, inhibition of RNA synthesis was immediate and total, suggesting that this is the primary target of allicin action.
TL;DR: Groups of thought disordered and non-thought disordered schizophrenic patients, unipolar affective patients and normal controls performed a lexical decision task involving the recognition of words immediately preceded (primed) by either an associated or an unrelated word.
TL;DR: A method for screening and comparing large numbers of unselected integration events for cell target sequences in retrovirus replication and reveals the presence of a number of strongly preferred integration targets.
TL;DR: It is found that the 73,000-dalton polypeptide can be dissociated from the complex with 0.5 M KI in the absence of detergent, indicating a peripheral association of this subunit with the membrane.
TL;DR: The findings indicate that rifampin resistance may not be an innocuous mutation in some pseudomonads and that marked strains should be compared with wild-type parents before being used as monitors of parental strain survival.
Abstract: The fate of spontaneous chromosomal rifampin-resistant (Rifr) mutants of Pseudomonas putida and Pseudomonas fluorescens in sterile and live organic soil from which they were isolated was studied. In sterile native-soil assays, a Rifr mutant of P. putida showed no decrease in competitive fitness when compared with the wild-type parent. However, mutants of P. fluorescens were of two general categories. Group 1 showed no difference from the wild type in terms of growth rate, competitive fitness, and membrane protein composition. Group 2 showed a slower growth rate in both minimal and enriched media and an altered membrane protein profile. These mutants also demonstrated decreased competitive fitness compared with the wild-type strain. In live soil, the Rifr P. putida strain persisted throughout the 38-day test period with a decay rate of 0.7 log10 CFU/g of soil per 10 days. A group 1 Rifr P. fluorescens mutant maintained its inoculated titer for 7 to 10 days and then decayed at a rate of 0.2 to 0.4 log10 CFU/g of soil per 10 days. A group 2 Rifr P. fluorescens mutant remained at its titer for 1 to 5 days before decaying at a two- to threefold-faster rate. These findings indicate that rifampin resistance may not be an innocuous mutation in some pseudomonads and that marked strains should be compared with wild-type parents before being used as monitors of parental strain survival. Colonization of sterile soil with either the wild-type or mutant strain precluded normal colonization of the second added strain.(ABSTRACT TRUNCATED AT 250 WORDS) Images
TL;DR: Estimates of the amount of partial information that subjects have accumulated about a test stimulus at each intermediate moment during a reaction time trial provide deeper insights into the rate at which partial information is accumulated over time and into discrete versus continuous modes of information processing.
Abstract: Measurements of reaction time have played a major role in developing theories about the menial processes that underlie sensation, perception, memory, cognition, and action. The interpretation of reaction time data requires strong assumptions about how subjects trade accuracy for speed of performance and about whether there is a discrete or continuous transmission of information from one component process to the next. Conventional reaction time and speed-accuracy trade-off procedures are not, by themselves, sufficiently powerful to test these assumptions. However, the deficiency can be remedied in part through a new speed-accuracy decomposition technique. To apply the technique, one uses a hybrid mixture of (a) conventional reaction time trials in which subjects must process a given test stimulus with high accuracy and (b) peremptory response-signal trials in which subjects must make prompted guesses before stimulus processing has been finished. Data from this "titrated reaction time procedure" are then analyzed in terms of a parallel sophisticated-guessing model, under which normal mental processes and guessing processes are assumed to race against each other in producing overt responses. With the model, one may estimate the amount of partial information that subjects have accumulated about a test stimulus at each intermediate moment during a reaction time trial. Such estimates provide deeper insights into the rate at which partial information is accumulated over time and into discrete versus continuous modes of information processing. An application of speed-accuracy decomposition to studies of word recognition illustrates the potential power of the technique.
TL;DR: The in vitro and in vivo evaluation of ultrasound angioscopy is described, a new technique capable of providing dynamic, circumferential images of blood vessels, which is a major diagnostic modality for assessing vascular anatomy.
Abstract: The assessment of the presence and severity of disease in the peripheral and coronary arteries currently requires contrast angiography. Although computed tomography, noninvasive ultrasound imaging and fiberoptic angioscopy may allow visualization of certain portions of the arteries, these techniques have limitations.1–3 Contrast angiography, which yields only long-axis images of the blood vessel lumen, continues to be the major diagnostic modality for assessing vascular anatomy. In this report we describe the in vitro and in vivo evaluation of ultrasound angioscopy, a new technique capable of providing dynamic, circumferential images of blood vessels.
TL;DR: The relative motion of selected carpal bones and the radius was studied using five cadaver specimens labeled with metal markers to precisely quantitate their motions and it is theorized that the proximal row functions as a variable geometry intercalated segment between the distal row and theradius-triangular fibrocartilage.
Abstract: The relative motion of selected carpal bones and the radius was studied using five cadaver specimens labeled with metal markers to precisely quantitate their motions. Data was obtained by means of a combination of orthoradiography, sonic digitization, and computer analysis. We conclude that the wrist functions as two carpal rows with the distal row bones relatively tightly bound to one another and the proximal row bones less so but still moving together. Therefore, we theorize that the proximal row functions as a variable geometry intercalated segment between the distal row and the radius-triangular fibrocartilage.
TL;DR: Intracranial VA dissection causes four overlapping syndromes: (1) brainstem infarcts are usually due to subintimal dissection extending into the basilar artery, affect younger patients, and often are single fatal events; (2) SAH is due toSubadventitial or transmural dissection; (3) aneurysms cause mass effect on the brainstem and lower cranial nerves; and (4) chronic dissections due to connective
Abstract: We describe four patients and review prior reports to clarify the clinical, radiographic, and pathologic findings of intracranial vertebral artery (VA) dissection. A 43-year-old man and a 33-year-old woman had chronic bilateral VA dissecting aneurysms. The man had multiple episodes of subarachnoid hemorrhage (SAH) and necropsy showed multiple dissections and defects in the internal elastica. The woman had many brainstem TIAs and strokes during 3 years. Two other patients had SAH and unilateral dissections. Intracranial VA dissection causes four overlapping syndromes: (1) brainstem infarcts are usually due to subintimal dissection extending into the basilar artery, affect younger patients, and often are single fatal events; (2) SAH is due to subadventitial or transmural dissection; (3) aneurysms cause mass effect on the brainstem and lower cranial nerves; and (4) chronic dissections due to connective tissue defects cause extensive bilateral aneurysms and repeated TIAs, small strokes, and SAH.
TL;DR: It is demonstrated that IL-1 pretreatment protects granulocytopenic mice against lethal pseudomonas infection and suggest that this protection occurs through a noncellular mechanism.
Abstract: Natural and synthetic immunomodulators that increase nonspecific resistance to infection induce interleukin 1 (IL-1) production. Therefore, we investigated the effect of the administration of IL-1 on the survival of lethally infected granulocytopenic mice. Mice with cyclophosphamide-induced granulocytopenia were injected with approximately 10(7) Pseudomonas aeruginosa in the thigh muscle at time 0; gentamicin was administered 6 hr and 23 hr later. When recombinant human IL-1 beta (one of the two forms of IL-1) was given as a single i.p. injection 24 hr before the infection, survival was increased. Using 80 ng of IL-1 beta per mouse, survival compared to control animals was 98% vs. 71% at 24 hr, 98% vs. 60% at 30 hr, 86% vs. 36% at 36 hr, and 61% vs. 11% at 48 hr (P less than 0.001) after the infection. No effect of IL-1 was observed when it was given 0.5 hr before or 6 hr after the infection. Animals not treated with gentamicin also benefited from the IL-1. Administration of the cyclooxygenase inhibitor ibuprofen did not affect the activity of IL-1. Numbers of bacteria cultured from the blood, thigh muscle, liver, spleen, and kidney were similar in IL-1-treated and control animals. Superoxide production by peritoneal macrophages was also similar in the two groups. These studies demonstrate that IL-1 pretreatment protects granulocytopenic mice against lethal pseudomonas infection and suggest that this protection occurs through a noncellular mechanism.