Alcohol 27 (2002) 53–61
0741-8329/02/$ – see front matter ? 2002 Elsevier Science Inc. All rights reserved.PII: S0741-8329(02)00212-4
Monocyte activation in alcoholic liver disease
Craig J. McClain a,b, *, Daniell B. Hill a , Zhenyuan Song a , Ion Deaciuc c
, Shirish Barve a
a
Department of Medicine, University of Louisville Medical Center, the b Veterans Administration, Louisville, KY 40292, USA
c
Department of Medicine, University of Kentucky Medical Center, Lexington, KY 40536, USA Received 18 December 2001; received in revised form 25 January 2002; accepted 9 February 2002
Abstract
Activated monocytes and macrophages have been postulated to play an important role in the pathogenesis of alcoholic liver disease (ALD). Monocyte activation can be documented by measurement of neopterin, adhesion cell molecules, and certain proinflammatory cy-tokines and chemokines. We first became interested in the role of monocytes and monocyte-derived cytokines in ALD in relation to al-tered zinc metabolism that occurs regularly in ALD. Patients with ALD have hypozincemia, which responds poorly to oral zinc supple-mentation. We have shown that in ALD monocytes make a low-molecular-weight substance that, when injected into rabbits, causes prominent hypozincemia. Subsequently, multiple cytokines [especially tumor necrosis factor (TNF) and interleukin (IL)-8] have been shown to be overproduced by monocytes in ALD. We initially showed that monocytes in ALD spontaneously produce TNF and overpro-duce TNF in response to a lipopolysaccharide (LPS) stimulus, and this could be attenuated by antioxidants in vitro and in vivo. Alter-ations in the endotoxin-binding protein LPS-binding protein, in CD14, and in the endotoxin receptor Toll-like receptor 4 all may play roles in enhanced proinflammatory cytokine signaling in ALD. Moreover, several groups have documented increased TNF receptor den-sity in monocytes in ALD. Inadequate negative regulation of TNF occurs at multiple levels in ALD. This includes decreased monocyte production of the important antiinflammatory cytokine IL-10 and blunted response to the antiinflammatory properties of adenosine. Fi-nally, generation of reactive oxygen species (which occurs during alcohol metabolism) and products of lipid peroxidation induce produc-tion of cytokines, such as TNF and IL-8. In conclusion, there are multiple overlapping potential mechanisms for enhanced proinflamma-tory cytokine prod uction by monocytes in ALD. We postulate that activation of monocytes and macrophages with subsequent proinflammatory cytokine production plays an important role in certain metabolic complications of ALD and is a component of the liver injury of ALD.? 2002 Elsevier Science Inc. All rights reserved.
Keywords: Alcoholic liver disease; Cytokines; Oxidative stress; Monocytes
1. Introduction
The research focus of our laboratory for more than 15years has been the activation of monocytes, macrophages,and Kupffer cells in alcoholic liver disease (ALD), subse-quent production of proinflammatory cytokines such as tu-mor necrosis factor (TNF), and consequent production of many of the metabolic complications and the liver injury of ALD (McClain et al., 1999). In this review, we will focus on the role of monocyte activation in ALD and thus the role of monocytes in the pathogenesis of systemic and clinical complications of ALD. Three components will be ad-dressed: (1) evidence for monocyte activation in ALD, (2)
potential mechanisms for monocyte activation in ALD, and (3) role of secreted monocyte products (e.g., cytokines) in the systemic sequelae of ALD. For this symposium, we have not addressed the role of other cell types, such as neu-trophils and lymphocytes, in the pathogenesis of liver in-jury, nor the role of Kupffer cells in liver injury. These areas have been reviewed extensively in other participants’ pa-pers in these proceedings. 2. Monocyte activation
There are several ways in which monocyte activation can be documented. One of the most widely used markers is the serum or urinary neopterin level (a nonspecific indicator of monocyte activation). Neopterin is a pyrazino-pyrimidine compound that is produced in large amounts by macro-phages after stimulation with interferon-gamma (IFN- ? ).Neopterin levels are consistently elevated in ALD (Luna-
*Corresponding author. Department of Internal Medicine, University of Louisville Medical Center, 550 S. Jackson St., ACB 3rd Floor, Louis-ville, KY 40292, USA. Tel.: ? 1-502-852-6991; fax: ? 1-502-852-0846. E-mail address
: craig.mcclain@https://www.doczj.com/doc/cc2915825.html, (C.J. McClain).Editor: T.R. Jerrells
54 C.J. McClain et al. / Alcohol 27 (2002) 53–61 Casado et al., 1997). Increased levels of adhesion cell mole-
cules such as leukocyte function-associated antigen (LFA)-3
are expressed on monocytes in patients with ALD and also
reflect monocyte activation (Luna-Casado et al., 1997).
Activated monocytes secrete proinflammatory cytokines,
which play a role in the liver injury and metabolic compli-
cations of ALD. In 1989, we first documented that periph-
eral blood monocytes obtained from patients with alcoholic
hepatitis (AH) spontaneously produce TNF, and they pro-
duce significantly more TNF after stimulation with li-popolysaccharide (LPS) than do control monocytes (Mc-
Clain & Cohen, 1989). We subsequently showed that
monocytes in AH have significantly more TNF mRNA in
both basal and LPS-stimulated states than do control mono-
cytes (Hill et al., 2000) (Fig. 1). Patients with AH have ele-
vated serum TNF levels, and elevated serum TNF levels
have been correlated with poor prognosis in AH (Bird et al.,
1990; Felver et al., 1990; Khoruts et al., 1991). Increased
TNF receptor gene expression has been documented by
Hanck et al. (2000) in peripheral blood monocytes obtained
from patients with alcoholic cirrhosis. They found that ex-
pression of TNF receptor message is directly related to the
severity of cirrhosis, as expressed by Child–Pugh staging.
This increased expression of both TNF receptors (p55 and
p75) occurred despite the fact that these patients with cir-
rhosis were abstinent for at least 6 months. Thus, once cir-
rhosis develops, the increased expression of TNF receptors
may act in a positive feedback loop to maintain the inflam-
matory response. Patients with AH, alcoholic cirrhosis, or
both have elevated serum levels of interleukin (IL)-6 and in-
creased monocyte IL-6 production (Deviere et al., 1990;
H ill et al., 1992). We showed that IL-6 levels correlated
well and directly with the clinical course of disease in pa-
tients with AH (Hill et al., 1992). Interleukin-8 is a neutro-
phil chemotactic peptide. Increased plasma and monocyte
IL-8 levels have been documented in ALD and have been
postulated to play a role in the neutrophil infiltration and ac-tivation in ALD (H ill et al., 1993; Jayatilleke & Shaw, 1998; Sheron et al., 1993). Patients with ALD also have in-creased monocyte production and serum concentrations of the beta chemokines monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1 (Devalaraja et al., 1999; Fisher et al., 1999). These chemo-kines play a critical role in the recruitment of leukocytes to sites of inflammation. We have shown that MCP-1 produc-tion by peripheral blood monocytes decreases as the clinical course of AH improves (Fig. 2). Moreover, a glutathione pro-drug and antioxidant (N-acetylcysteine) attenuates monocyte MCP-1 production (Devalaraja et al., 1999). We postulated that MCP-1 plays a role in the pathogenesis of ALD by re-cruiting and retaining monocytes within the liver.
In summary, there is extensive emerging literature from multiple laboratories documenting increased monocyte activa-tion in ALD, as manifested by increased monocyte neoptrin levels, increased adhesion molecule expression, and increased proinflammatory cytokine production, to name only a few.3. Mechanisms of monocyte activation and enhanced cytokine production
3.1. Endotoxin, lipopolysaccharide-binding protein, CD14, and Toll-like receptors in alcoholic liver disease Both portal vein and systemic endotoxemia are well doc-umented in ALD, with increased serum endotoxin levels noted even in patients with only fatty liver (Bigatello et al., 1987; Bode et al., 1987). Alcohol consumption increases gut permeability in both experimental animals and human beings (Bjarnason et al., 1984; Robinson et al., 1981). How-ever, the relative importance of endotoxin in ALD remains controversial. Why alcohol-dependent subjects should re-tain responsiveness to LPS instead of developing LPS toler-ance is unclear. Why alcohol-dependent persons with in-creased gut permeability and endotoxemia develop liver disease whereas patients with Crohn’s disease (also with in-creased gut permeability and endotoxemia) do not develop
liver injury is not understood (D’Inca et al., 1999; Parlesak Fig. 1. A. Monocytes from patients with alcoholic hepatitis (AH) had greater lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) production. These differences were present whether TNF protein was mea-sured by enzyme-linked immunosorbent assay (ELISA) (picograms per milliliter) or bioactivity (units per milliliter) by using the LM cell assay (ELISA shown here). *P? .05, AH compared with normals. Monocytes from patients with AH had spontaneous TNF production as well, but for normal subjects spontaneous TNF production by monocytes was below the lower detection limits of the assay (data not shown). B. Monocytes from patients with AH had spontaneous expression of TNF mRNA. Semiquanti-tative reverse transcriptase-polymerase chain reaction (RT-PCR) showing mRNA for TNF (top) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (positive control mRNA) (bottom). Lane 1–normal subject’s monocytes, no LPS added (spontaneous); Lane 2–normal subject’s mono-cytes, treated with LPS; Lane 3–AH patient’s monocytes, no LPS added (spontaneous); Lane 4–AH patient’s monocytes, treated with LPS. Adapted with permission from D. B. Hill, S. Barve, S. Joshi-Barve, & C. J. McClain, Increased monocyte NF-?B activation and tumor necrosis factor production in alcoholic hepatitis, Journal of Laboratory and Clinical Med-icine 135, pp. 387–395, Harcourt Health Sciences, ?2000.
C.J. McClain et al. / Alcohol 27 (2002) 53–61 55
et al., 1994). The role of LPS in the development of ALD,related to the discovery that the Toll-like receptor 4 (Tlr4) is the LPS receptor (Beutler, 2000), may now allow us to be-gin to unravel these questions.
Endotoxin has long been known to bind to an LPS-bind-ing protein (LBP) in the plasma, with LBP also being a he-patic acute-phase reactant (Su et al., 2000; Wurfel et al.,1997). Lipopolysaccharide-binding protein markedly en-hances the signaling of LPS when added to monocytes,macrophages, and Kupffer cells (Su et al., 2000; Wurfel et al., 1997). Lipopolysaccharide-binding protein binds to CD14, a glyocosyl-phosphatidylinositol-anchored protein that is expressed in mature myeloid cells and most macro-phages (Fenton & Golenbock, 1998; Landmann et al.,2000). The role of CD14 in LPS signaling has been unclear because it lacks a transmembrane-signaling domain (Fenton & Golenbock, 1998; Landmann et al., 2000). The recent discovery that Tlr4, a type 1 transmembrane protein, serves as an LPS receptor, which causes intracellular nuclear fac-tor-kappa B (NF- ? B) activation, now permits the detailed evaluation of LPS signaling in many disease states (Beutler,2000). Toll-like receptor 4 spans the cytoplasmic mem-brane, and its intracellular domain is quite similar to that of the IL-1 receptor. A large family of Toll-like receptors has now been identified and cloned. The cytoplasmic tail of Tlr4 recruits the adapter protein MyD88 and the serine–threonine kinase IL-1 receptor-associated kinase (IRAK).The latter interacts with TNF receptor-associated factor 6(TRAF-6), which bridges to NF- ? B-inducing kinase (NIK),which activates the I- ? B kinase (IKK) complex with subse-quent NF- ? B activation (Fig. 3) (Anderson, 2000; Antal-Szalmas, 2000; Bowie & O’Neill, 2000; Fenton & Golen-bock, 1998; Landmann et al., 2000; Means et al., 2000).The functional roles of LBP and CD14 are complex and depend on experimental paradigms. The LBP knockout mice seem to be resistant to LPS-galactosamine lethality,but highly sensitive to Salmonella
-induced lethality (Means et al., 2000). The CD14 knockout mice are consistently re-sistant to LPS toxicity, and CD14 overexpression sensitizes the mice to LPS lethality (Means et al., 2000). Importantly,CD14 also serves as a phospholipid “shuttle” protein (Land-mann et al., 2000). Some of the effects of dietary lipid and lecithin on hepatotoxicity in ALD may be through lipid ef-fects on CD14. Thus far, LPS toxicity and TNF production seem to be closely related to Tlr4 receptor density, and mu-tants lacking functional Tlr4 are resistant to LPS toxicity and lethality and do not produce TNF in response to LPS (Beutler, 2000).
Animal models of ALD demonstrate increased LBP and CD14 (Enomoto et al., 1998; Su et al., 1998), and patients with AH have increased serum LBP levels (Fujimoto et al.,
2000). Thurman and colleagues have shown that female rats
Fig. 2. Monocytes from 15 patients with acute alcoholic hepatitis (AH ) had constitutive monocyte chemoattractant protein (MCP)-1 production, as assessed by MCP-1 concentrations measured in monocyte culture supernatants after overnight (20-h) incubation. In contrast, monocytes from normal sub-jects did not spontaneously release detectable MCP-1 into the monocyte culture supernatant. The constitutive MCP-1 production by AH patient mono-cytes decreased significantly over time as the patients improved clinically and with abstinence. Serum bilirubin levels declined in parallel with decreased MCP-1 production. Adapted with permission from M. N. Devalaraja, C. J. McClain, S. Barve, K. Vaddi, & D. B. Hill, Increased monocyte MCP-1 pro-duction in acute alcoholic hepatitis, Cytokine 11, pp. 875–881, Harcourt, Inc., ?1999.
56 C.J. McClain et al. / Alcohol 27 (2002) 53–61
fed an ethanol diet have not only greater liver injury but also more endotoxemia and greater Kupffer cell expression of TNF and CD14 mRNA and NF- ? B activation in compari-son with findings for controls (Kono et al., 2000). Increases in LBP and CD14 mRNA occur after only 24 to 48 h of eth-anol feeding to rats, supporting the suggestion that these binding proteins may play a role in the liver damage instead of merely being a consequence of liver injury (Lukkari et al., 1999). Moreover, increased serum levels of soluble CD14 (sCD14) have been reported in ALD, and increased monocyte production of sCD14 correlates with severity of ALD (Oesterreicher et al., 1995). Finally, research findings from Thurman’s laboratory have shown that mice lacking CD14 and mice lacking functional Tlr4 are protected against early ethanol-induced hepatotoxicity (Uesugi et al.,2001; Yin et al., 2001). 3.2. Direct effects of alcohol
There is an apparent dichotomous effect of alcohol on monocyte activation and subsequent proinflammatory cy-tokine production. Initial work from investigators at Louisi-ana State University H ealth Sciences Center in New Or-leans showed that acute exposure of monocytes and macrophages to alcohol inhibits LPS-stimulated TNF pro-duction (Nelson et al., 1989). Moreover, when experimental animals are given an acute dose of alcohol they also evi-dence depressed serum concentrations of TNF after LPS stimulation (D’Souza et al., 1989). In contrast, our group first showed that peripheral blood monocytes obtained from patients with diagnoses of chronic alcohol abuse and AH have spontaneous TNF production and enhanced LPS-stim-ulated TNF production (McClain & Cohen, 1989). More-over, rats chronically fed alcohol have significantly increased serum TNF production after LPS injection (H onchel et al.,1992). Results of studies by Szabo et al. (1996) confirmed
the suppressive effects of acute ethanol exposure on mono-cyte proinflammatory cytokine production.
Recent research findings from Kolls’ laboratory, with the use of an in vitro system of ethanol exposure, helped clarify some of these seemingly disparate observations concerning acute versus chronic effects of ethanol (Zhang et al., 2001).This group cultured Mon Mac 6 cells (a human monocyte cell line) in varying concentrations of ethanol for 1 to 7 days.They subsequently evaluated TNF production after LPS or phorbol myristate acetate stimulation. They also measured generation of reactive oxygen species (ROS) in these cells over time. They found that acute ethanol exposure modestly inhibits TNF production, as has been shown by their group and others. H owever, by day 6, ethanol treatment signifi-cantly up-regulates TNF production. This increase in TNF production is associated with increased generation of ROS.The increased TNF production could be inhibited by antioxi-dants such as N -acetylcysteine. Taken cumulatively, these findings support the suggestion that acute exposure to ethanol per se does not cause monocyte activation or augment proin-flammatory cytokine production. In contrast, chronic ethanol exposure and metabolism, with generation of ROS, does lead to enhanced TNF production. This research from Kolls’ labo-ratory further supports the role for ROS in the enhanced monocyte and cytokine production observed in ALD. 3.3. Oxidative stress
Alcohol metabolism is associated with increased oxidative stress (Meagher et al., 1999). Administration of ethanol to healthy volunteers is associated with an increase in isoprostane levels (marker of lipid peroxidation), and patients with AH have very elevated isoprostane levels (Hill et al., 1999; Meagher et al., 1999). Moreover, products of lipid peroxidation have been shown to stimulate production of the chemokine IL-8 in human monocytes (Jayatilleke & Shaw, 1998). Patients with diagnoses of chronic alcohol abuse and ALD frequently have decreased levels of nutritional antioxidants such as hepatic glu-tathione (Situnayake et al., 1990). The activation of gene tran-scription of critical cytokines and chemokines, such as TNF,IL-1, IL-8, and MCP-1, is closely associated with the oxidative stress-sensitive transcription factor NF- ? B (Mihm et al., 1995;Sato et al., 1996; Thanos & Maniatis, 1995; Tran-Thi et al.,1995). This supports the suggestion that oxidative stress-sensi-tive transcription factors such as NF- ? B may be potential sites of intervention in the treatment of inflammatory diseases, in-cluding AH (Hill et al., 2000). Indeed, we have used both the chain-breaking antioxidant vitamin E and a glutathione-pro-drug, N
-acetylcysteine, to down-regulate TNF production in monocytes in vitro (Hill et al., 1999). Moreover, study findings from our laboratory have shown that intravenous administra-tion of the glutathione prodrug procysteine decreases cytokine production in stable alcoholic cirrhosis (Pena et al., 1999). In Thurman’s laboratory, procysteine has been used to prevent liver injury in the intragastric ethanol-feeding mouse model of
ALD (Iimuro et al., 2000).
Fig. 3. Lipopolysaccharide interactions with monocytes and the Toll sig-naling pathway. I ?B ? I-kappaB; IL-1 ? interleukin-1; IL-6 ? interleu-kin-6; IRAK ? interleukin-1 receptor-associated kinase; LBP ?lipopolysaccharide-binding protein; LPS ? lipopolysaccharide; NF-?B ?nuclear factor-kappa B; Tlr4 ? Toll-like receptor 4; TNF ? tumor necrosis factor; TRAF6 ? tumor necrosis factor receptor-associated factor 6.
C.J. McClain et al. / Alcohol 27 (2002) 53–6157
3.4. Portal hypertension
A major potential complication of ALD is portal hyperten-sion. There are compelling study findings in experimental animals to show that portal hypertension itself (unrelated to ethanol intake) enhances monocyte activation and proinflam-matory cytokine production. In one study (Perez del Pulgar et al., 2000), rats with portal hypertension, induced by partial portal vein ligation, were administered low-dose endotoxin. Peak plasma TNF levels were increased ninefold in rats with portal hypertension compared with findings for sham-oper-ated rats. Rats with portal hypertension had a marked up-regu-lation of CD11b/CD18 expression on their monocytes com-pared with findings for sham-operated rats. Moreover, the rats with portal hypertension developed significantly worse liver injury. Peripheral blood monocytes were then cultured and stimulated in vitro with LPS. Similar to in vivo study findings, monocytes from portal vein–ligated rats produced signifi-cantly more TNF than did monocytes in sham-operated rats. This supports the suggestion that somehow portal hypertension primes peripheral blood monocytes to produce proinflamma-tory cytokines such as TNF (Perez del Pulgar et al., 2000).
3.5. Inadequate inhibitory factors
The importance of ROS in the development of ALD is well documented. The role of ROS in modulation of NF-?B activation is also clear. Patients with ALD frequently have inadequate levels of antioxidants, such as vitamin E, glu-tathione, and selenium (H ill et al., 2000; McClain et al., 1991). Moreover, in vitro and in vivo antioxidant supple-mentation has been shown to inhibit monocyte NF-?B acti-vation and proinflammatory cytokine production. Thus, in-adequate levels of antioxidants may play a role in monocyte activation,and antioxidant therapy may represent a target for therapeutic intervention in ALD (Hill et al., 2000).
Interleukin-10 is a critical antiinflammatory cytokine that also seems to have antifibrotic activity in liver disease. Le Moine and co-workers first reported that peripheral blood monocytes obtained from patients with alcoholic cirrhosis had decreased monocyte production of IL-10 (Le Moine et al., 1995). They performed in vitro studies, results of which dem-onstrated that defective IL-10 secretion by monocytes in ALD might be involved in the TNF overproduction observed in ALD. Recently, this same group showed that adenosine (which has antiinflammatory properties) inhibits TNF release and increases IL-10 production in LPS-stimulated whole blood cultures obtained from volunteers stimulated with LPS, but not from patients with cirrhosis (Le Moine et al., 1999). They determined that there was increased circulating adeno-sine deaminase activity in the plasma of patients with cirrhosis that accelerated adenosine breakdown and thus blunted the an-tiinflammatory response in patients with cirrhosis (Le Moine et al., 1995). This decreased IL-10 response could play a ma-jor role in the monocyte activation and increased TNF produc-tion observed in ALD (as well as in the hepatic fibrotic re-sponse in these patients).4. Monocyte activation/cytokine systemic effects
Increased circulating levels of cytokines have been pos-tulated to cause many of the metabolic and nutritional ab-normalities observed in ALD, especially in AH, and in more decompensated liver disease (Hill et al., 1997; McClain et al., 1999). Thus, abnormalities, such as fever, anorexia, muscle breakdown and wasting, and altered mineral metab-olism (to name only a few), are likely, at least partially, to be mediated by products from activated macrophages (Fig.
4). We will briefly review alterations in clotting, mineral metabolism, visceral proteins, hypermetabolism, and anor-exia in relation to cytokines and ALD.
4.1. Clotting
Tissue factor (TF) is a membrane-bound glycoprotein produced by circulating monocytes in response to inflam-matory stimulus, and TF triggers the extrinsic pathway of the clotting system (Saliola et al., 1998). Hyperfibrinolysis and a prothrombotic state are well documented in alcoholic cirrhosis, with a major complication being portal vein thrombosis. Monocyte TF levels were shown to be elevated in 33 patients with cirrhosis, and they increased in a step-wise fashion in conjunction with worsening severity of liver disease as assessed by Child–Pugh staging (Saliola et al., 1998). In this study, TF levels also correlated with endo-toxin concentrations. Tissue factor mRNA was detected in some monocytes from patients with cirrhosis, but not in monocytes from control subjects, supporting the suggestion that monocytes in patients with cirrhosis are already in a state of activation. These same investigators postulated that oxidative stress may be playing a role in this enhanced monocyte TF expression. They therefore treated patients with cirrhosis with standard therapy or standard therapy plus 300 mg of vitamin E twice daily (Ferro et al., 1999). They documented that in vivo vitamin E treatment de-creased monocyte TF antigen and TF activity as well as a marker of oxidative stress (isoprostane levels).
4.2. Minerals
Cytokines, such as TNF and IL-1, generally cause a de-crease in the serum zinc concentration and an internal redis-tribution of zinc, with zinc being sequestered in the liver and being lost from other tissues, such as bone marrow and thymus (Gaetke et al., 1997; Goldblum et al., 1987; Mc-Clain et al., 1993). This internal redistribution of zinc is thought to facilitate priority protein synthesis in the liver and to make the plasma a less favorable environment for bacterial growth (“zinc withholding”) (Gaetke et al., 1997; Goldblum et al., 1987; McClain et al., 1993). The decrease in serum zinc and increase in hepatic zinc levels is due to a cytokine-mediated increase in hepatic metallothionein pro-duction. Metallothionein is an acute-phase, metal-binding protein, and metallothionein knockout mice do not demon-strate hypozincemia after cytokine stimulation (Gaetke et al., 1997; McClain et al., 1993). Frequently, there is an in-
58 C.J. McClain et al. / Alcohol 27 (2002) 53–61
crease in urinary zinc loss that can contribute to overall zinc deficits in patients with increased cytokine activity. Patients with liver disease regularly have decreased serum zinc con-centrations and increased urinary zinc losses (McClain et al., 1992). We have shown that administration of low-dose endotoxin to healthy volunteers leads to a hypozincemia that is similar in magnitude to that seen in alcoholic cirrho-sis, and we postulate that the endotoxemia observed in ALD plays an etiologic role in the hypozincemia of ALD. This zinc deficiency may contribute to the anorexia, sexual dys-function, and immune impairment reported in liver disease (McClain et al., 1992). 4.3. Visceral proteins
With elevated cytokine levels, there is generally a de-pression in plasma proteins (often used as indicators of nu-tritional status), including albumin, transferrin, prealbumin,and retinol-binding protein. This reduction in protein occurs initially because cytokines such as TNF cause an increase in endothelial permeability, which then causes a decrease in these visceral proteins (Hennig et al., 1988). Proinflamma-tory cytokines also decrease production (mRNA) of these visceral proteins, which partially accounts for long-term de-pression of these proteins (Boosalis et al., 1989). At the same time that there is a decrease in these visceral proteins,there is also an increase in hepatic acute-phase proteins.Certain of these acute-phase reactants play a role in attenu-ating the ongoing toxic effects of cytokines, an example be-ing ? 1
-acid glycoprotein, which attenuates toxic effects of TNF (Libert et al., 1994).
4.4. Hypermetabolism, hypercatabolism
Increased cytokine production can induce a hypermeta-bolic/hypercatabolic state. For example, TNF infusion into experimental animals causes a decrease in protein synthesis,with an overall increase in net protein breakdown (Sakurai et al., 1994). This may relate to the hypermetabolism and wasting seen in ALD (John et al., 1989), especially with AH.
4.5. Anorexia, decreased gastric emptying
Cytokines frequently induce anorexia; indeed, TNF was initially termed cachectin (Beutler & Cerami, 1986). Sev-eral cytokines, such as IL-1 and TNF, also impair gastric emptying, and impaired gastric emptying occurs as a com-plication of liver disease (Galati et al., 1994; Isobe et al.,1994; Suto et al., 1994). Some patients will respond to pro-kinetic agents such as metoclopramide hydrochloride (Reglan). Leptin is a hormone that induces anorexia. Leptin levels normally increase after eating and decrease with fast-ing. However, LPS and cytokines such as TNF also induce leptin (Sarraf et al., 1997). During infection and inflamma-tion, leptin levels can be inappropriately elevated during fasting, leading to the anorexia of inflammation. Thus,known increases in LPS and TNF may lead to anorexia in ALD by means of this leptin-mediated pathway. 5. Conclusions and future directions
Monocyte activation is well documented in patients with
ALD. The mechanisms for this are multiple, as outlined in
Fig. 4. Patients with alcoholic liver disease have systemic complications that are identical with known metabolic actions of inflammatory cytokines, such as tumor necrosis factor and interleukin-1. Adapted with permission from C. J. McClain, S. Barve, I. Deaciuc, M. Kugelmas, & D. Hill, Cytokines in alcoholic liver disease, Seminars in Liver Disease 19, pp. 205–219, Thieme Medical Publishers, ?1999.
C.J. McClain et al. / Alcohol 27 (2002) 53–6159
this review. H owever, critical questions such as why pa-tients with liver disease (a condition in which monocytes are continually exposed to endotoxin) do not develop endot-oxin tolerance remain unanswered. The observed monocyte activation, with its subsequent proinflammatory cytokine production, plays a role not only in the liver injury in ALD but in many systemic complications of ALD, such as fever, anorexia, and hypozincemia. Blocking monocyte activation and proinflammatory cytokine production is one likely fu-ture target for therapeutic intervention in ALD.
There are several important areas that require future in-vestigation, including (1) the effects of chronic alcohol abuse on the complex signaling pathways leading to en-hanced proinflammatory cytokine production; (2) the role of limited IL-10 production and signaling, as well as of other inadequate antiinflammatory responses; (3) the poten-tial role of oxidative stress in monocyte activation in ALD;
(4) the role of portal hypertension and portal systemic shunting in monocyte activation; (5) the role of monocyte activation in the metabolic complications of ALD; (6) po-tential therapeutic effects of drugs that attenuate monocyte activation and proinflammatory cytokine production; and (7) possible targeting of antiinflammatory drugs to mono-cytes/macrophages.
Acknowledgments
This research was supported by the National Institutes of H ealth grants AA01762, AA10496, AA00190, AA12314, and AA00205, and the Department of Veterans Affairs. References
Anderson, K. V. (2000). Toll signaling pathways in the innate immune re-sponse. Curr Opinion Immunol 12, 13–19.
Antal-Szalmas, P. (2000). Evaluation of CD14 in host defence. Eur J Clin Invest30, 167–179.
Beutler, B. (2000). Tlr4: central component of the sole mammalian LPS sensor. Curr Opin Immunol12, 20–26.
Beutler, B., & Cerami, A. (1986). Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature320, 584–588. Bigatello, L. M., Broitman, S. A., Fattori, L., Di Paoli, M., Pontello, M., Bevilacqua, G., & Nespoli, A. (1987). Endotoxemia, encephalopathy, and mortality in cirrhotic patients. Am J Gastroenterol82, 11–15. Bird, G. L. A., Sheron, N., Goka, A. K., Alexander, G. J., & Williams, R. S. (1990). Increased plasma tumor necrosis factor in severe alco-holic hepatitis. Ann Intern Med112, 917–920.
Bjarnason, I., Peters, T. J., & Wise, R. J. (1984). The leaky gut of alcohol-ism: possible route of entry for toxic compounds. Lancet1, 179–182. Bode, C., Kugler, V., & Bode, J. C. (1987). Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess. J Hepatol4, 8–14.
Boosalis, M. G., Ott, L., Levine, A. S., Slag, M. F., Morley, J. E., Young,
B., & McClain,
C. J. (1989). Relationship of visceral proteins to nutri-
tional status in chronic and acute stress. Crit Care Med17, 741–747. Bowie, A., & O’Neill, L. A. J. (2000). The interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-inflammatory interleu-kins and microbial products. J Leukoc Biol67, 508–514.Devalaraja, M. N., McClain, C. J., Barve, S., Vaddi, K., & H ill, D. B.
(1999). Increased monocyte MCP-1 production in acute alcoholic hep-atitis. Cytokine11, 875–881.
Deviere, J., Content, J., Denys, C., Vandenbussche, P., Schandene, L., Wy-bran, J., & Dupont, E. (1990). Excessive in vitro bacterial lipopolysac-charide-induced production of monokines in cirrhosis. Hepatology 11, 628–634.
D’Inca, R., Di Leo, V., Corrao, G., Martines, D., D’Odorico, A., Mestriner,
C., Venturi, C., Longo, G., & Sturniolo, G. C. (1999). Intestinal perme-
ability test as a predictor of clinical course in Crohn’s disease. Am J Gastroenterol94, 2956–2960.
D’Souza, N. B., Bagby, G. J., Nelson, S., Lang, C. H., & Spitzer, J. J.
(1989). Acute alcohol infusion suppresses endotoxin-induced tumor necrosis factor. Alcohol Clin Exp Res13, 295–298.
Enomoto, N., Ikejima, K., Bradford, B., Rivera, C., Kono, H., Brenner,
D. A., & Thurman, R. G. (1998). Alcohol causes both tolerance and
sensitization of rat Kupffer cells via mechanisms dependent on endot-oxin. Gastroenterology 115, 443–451.
Felver, M. E., Mezey, E., McGuire, M., Mitchell, M. C., Herlong, H. F., Veech, G. A., & Veech, R. L. (1990). Plasma tumor necrosis factor al-pha predicts decreased long-term survival in severe alcoholic hepatitis.
Alcohol Clin Exp Res14, 255–259.
Fenton, M. J., & Golenbock, D. T. (1998). LPS-binding proteins and recep-tors. J Leukoc Biol64, 25–32.
Ferro, D., Basili, S., Praticó, D., Iuliano, L., FitzGerald, G. A., & Violi, F.
(1999). Vitamin E reduces monocyte tissue factor expression in cir-rhotic patients. Blood93, 2945–2950.
Fisher, N. C., Neil, D. A., Williams, A., & Adams, D. H. (1999). Serum concentrations and peripheral secretion of the beta chemokines mono-cyte chemoattractant protein 1 and macrophage inflammatory protein 1? in alcoholic liver disease. Gut45, 416–420.
Fujimoto, M., Uemura, M., Nakatani, Y., Tsujita, S., H oppo, K., Tama-gawa, T., Kitano, H., Kikukawa, M., Ann, T., Ishii, Y., Kojima, H., Sakurai, S., Tanaka, R., Namisaki, T., Noguchi, R., Higashino, T., Kiku-chi, E., Nishimura, K., Takaya, A., & Fukui, H. (2000). Plasma endot-oxin and serum cytokine levels in patients with alcoholic hepatitis: rela-tion to severity of liver disturbance. Alcohol Clin Exp Res24, 48S–54S. Gaetke, L. M., McClain, C. J., Talwalkar, R. T., & Shedlofsky, S. I. (1997).
Effects of endotoxin on zinc metabolism in human volunteers. Am J Physiol272, E952–E956.
Galati, J. S., Holdeman, K. P., Dalrymple, G. V., Harrison, K. A., & Quig-ley, E. M. M. (1994). Delayed gastric emptying of both the liquid and solid components of a meal in chronic liver disease. Am J Gastroen-terol89, 708–711.
Goldblum, S. E., Cohen, D. A., Jay, M., & McClain, C. J. (1987). Interleu-kin-1-induced depression of iron and zinc: role of granulocytes and lactoferrin. Am J Physiol252, E27–E32.
Hanck, C., Glatzel, M., Singer, M. V., & Rossol, S. (2000). Gene expres-sion of TNF-receptors in peripheral blood mononuclear cells of pa-tients with alcoholic cirrhosis. J Hepatol32, 51–57.
Hennig, B., Honchel, R., Goldblum, S. E., & McClain, C. J. (1988). Tumor necrosis factor–mediated hypoalbuminemia in rabbits. J Nutr118, 1586–1590.
H ill, D., Shedlofsky, S., McClain, C., Diehl, A. M., & Tsukamoto, H.
(1997). Cytokines and liver disease. In D. G. Remick, & J. S. Friedland (Eds.), Cytokines in Health and Disease (2nd ed., revised and ex-panded) (pp. 401–425). New York: Marcel Dekker.
Hill, D. B., Barve, S., Joshi-Barve, S., & McClain, C. J. (2000). Increased monocyte nuclear factor-kappaB activation and tumor necrosis factor production in alcoholic hepatitis. J Lab Clin Med 135, 387–395. Hill, D. B., Devalaraja, R., Joshi-Barve, S. J., Barve, S., & McClain, C. J.
(1999). Antioxidants attenuate nuclear factor-kappa B activation and tumor necrosis factor-alpha production in alcoholic hepatitis patient monocytes and rat Kupffer cells, in vitro. Clin Biochem32, 563–570. Hill, D. B., Marsano, L., Cohen, D., Allen, J., Shedlofsky, S., & McClain,
C. J. (1992). Increased plasma interleukin-6 concentrations in alcoholic
hepatitis. J Lab Clin Med119, 547–552.
60 C.J. McClain et al. / Alcohol 27 (2002) 53–61
Hill, D. B., Marsano, L. S., & McClain, C. J. (1993). Increased plasma in-terleukin-8 concentrations in alcoholic hepatitis. Hepatology18, 576–580.
Honchel, R., Ray, M. B., Marsano, L., Cohen, D., Lee, E., Shedlofsky, S., & McClain, C. J. (1992). Tumor necrosis factor in alcohol enhanced endotoxin liver injury. Alcohol Clin Exp Res16, 665–669.
Iimuro, Y., Bradford, B. U., Yamashina, S., Rusyn, I., Nakagami, M., Enomoto, N., Kono, H., Frey, W., Forman, D., Brenner, D., & Thur-man, R. G. (2000). The glutathione precursor L-2-oxothiazolidine-4-carboxylic acid protects against liver injury due to chronic enteral ethanol exposure in the rat. Hepatology 31, 391–398.
Isobe, H., Sakai, H., Satoh, M., Sakamoto, S., & Nawata, H. (1994). De-layed gastric emptying in patients with liver cirrhosis. Dig Dis Sci 39, 983–987.
Jayatilleke, A., & Shaw, S. (1998). Stimulation of monocyte interleukin-8 by lipid peroxidation products: a mechanism for alcohol-induced liver injury. Alcohol16, 119–123.
John, W. J., Phillips, R., Ott, L., Adams, L. J., & McClain, C. J. (1989).
Resting energy expenditure in patients with alcoholic hepatitis. JPEN J Parenter Enteral Nutr 13, 124–127.
Khoruts, A., Stahnke, L., McClain, C. J., Logan, G., & Allen, J. I. (1991).
Circulating tumor necrosis factor, interleukin-1 and interleukin-6 con-centrations in chronic alcoholic patients. Hepatology13, 267–276. Kono, H., Wheeler, M. D., Rusyn, I., Lin, M., Seabra, V., Rivera, C. A., Bradford, B. U., Forman, D. T., & Thurman, R. G. (2000). Gender dif-ferences in early alcohol-induced liver injury: role of CD14, NF-?B, and TNF-?. Am J Physiol Gastrointest Liver Physiol278, G652–G661. Landmann, R., Muller, B., & Zimmerli, W. (2000). CD14, new aspects of ligand and signal diversity. Microbes Infect2, 295–304.
Le Moine, O., Marchant, A., De Groote, D., Azar, C., Goldman, M., & Deviere, J. (1995). Role of defective monocyte interleukin-10 release in tumor necrosis factor-alpha overproduction in alcoholic cirrhosis.
Hepatology22, 1436–1439.
Le Moine, O., Quertinmont, E., Gulbis, B., & Deviere, J. (1999). Blunted anti-inflammatory response to adenosine in alcoholic cirrhosis. J Hepa-tol31, 457–463.
Libert, C., Brouckaert, P., & Fiers, W. (1994). Protection by ?1-acid glyco-protein against tumor necrosis factor–induced lethality. J Exp Med180, 1571–1575.
Lukkari, T. A., Jarvelainen, H. A., Oinonen, T., Kettunen, E., & Lindros, K. O. (1999). Short-term ethanol exposure increases the expression of Kupffer cell CD14 receptor and lipopolysaccharide binding protein in rat liver. Alcohol Alcohol34, 311–319.
Luna-Casado, L., Diez-Ruiz, A., Gutierrez-Gea, F., Santos-Perez, J. L., Rico-Irles, J., Wachter, H., & Fuchs, D. (1997). Increased peripheral mononuclear cells expression of adhesion molecules in alcoholic cir-rhosis: its relation to immune activation. J Hepatol 27, 477–483. McClain, C. J., Barve, S., Deaciuc, I., Kugelmas, M., & Hill, D. (1999).
Cytokines in alcoholic liver disease. Semin Liver Dis19, 205–219. McClain, C. J., & Cohen, D. A. (1989). Increased tumor necrosis factor pro-duction by monocytes in alcoholic hepatitis. Hepatology9, 349–351. McClain, C. J., Kasarskis, E. J., & Marsano, L. (1992). Zinc and alcohol. In R. R. Watson, & B. Watzl (Eds.), Nutrition and Alcohol (pp. 281–307).
Boca Raton, FL: CRC Press.
McClain, C. J., Marsano, L., Burk, R. F., & Bacon, B. (1991). Trace metals in liver disease. Semin Liver Dis11, 321–339.
McClain, C. J., McClain, M. L., Boosalis, M. G., & H ennig, B. (1993).
Zinc and the stress response. Scand J Work Environ Health19 Suppl 1, 132–133.
Meagher, E. A., Barry, O. P., Burke, A., Lucey, M. R., Lawson, J. A., Rokach, J., & FitzGerald, G. A. (1999). Alcohol-induced generation of lipid peroxidation products in humans. J Clin Invest104, 805–813. Means, T. K., Golenbock, D. T., & Fenton, M. J. (2000). The biology of Toll-like receptors. Cytokine Growth Factor Rev11, 219–232. Mihm, S., Galter, D., & Droge, W. (1995). Modulation of transcription fac-tor NF ?B activity by intracellular glutathione levels and by variations of the extracellular cysteine supply. FASEB J 9, 246–252.Nelson, S., Bagby, G., & Summer, W. R. (1989). Alcohol suppresses li-popolysaccharide-induced tumor necrosis factor activity in serum and lung. Life Sci44, 673–676.
Oesterreicher, C., Pfeffel, F., Petermann, D., & Muller, C. (1995). In-creased in vitro production and serum levels of the soluble lipopolysac-charide receptor sCD14 in liver disease. J Hepatol 23, 396–402. Parlesak, A., Bode, J. C., & Bode, C. (1994). Parallel determination of gut permeability in man with Mr 400, Mr 1500, Mr 4000 and Mr 10,000 polyethylene glycol. Eur J Clin Chem Clin Biochem 32, 813–820. Pena, L. R., H ill, D. B., & McClain, C. J. (1999). Treatment with glu-tathione precursor decreases cytokine activity. JPEN J Parenter En-teral Nutr23, 1–6.
Perez del Pulgar, S., Pizcueta, P., Engel, P., & Bosch, J. (2000). Enhanced monocyte activation and hepatotoxicity in response to endotoxin in portal hypertension. J Hepatol32, 25–31.
Robinson, G. M., Orrego, H., Israel, Y., Devenyi, P., & Kapur, B. M.
(1981). Low-molecular-weight polyethylene glycol as a probe of gas-trointestinal permeability after alcohol ingestion. Dig Dis Sci26, 971–977.
Sakurai, Y., Zhang, X.-J., & Wolfe, R. R. (1994). Effect of tumor necrosis factor on substrate and amino acid kinetics in conscious dogs. Am J Physiol266, E936–E945.
Saliola, M., Lorenzet, R., Ferro, D., Basili, S., Caroselli, C., Santo, A. D., Sallese, M., & Violi, F. (1998). Enhanced expression of monocyte tis-sue factor in patients with liver cirrhosis. Gut43, 428–432.
Sarraf, P., Frederich, R. C., Turner, E. M., Ma, G., Jaskowiak, N. T., Rivet,
D. J. III, Flier, J. S., Lowell, B. B., Fraker, D. L., & Alexander, H. R.
(1997). Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J Exp Med185, 171–175.
Sato, M., Miyazaki, T., Nagaya, T., Murata, Y., Ida, N., Maeda, K., & Seo,
H. (1996). Antioxidants inhibit tumor necrosis factor-alpha mediated
stimulation of interleukin-8, monocyte chemoattractant protein-1, and collagenase expression in cultured human synovial cells. J Rheumatol 23, 432–438.
Sheron, N., Bird, G., Koskinas, J., Portmann, B., Ceska, M., Lindley, I., & Williams, R. (1993). Circulating and tissue levels of the neutrophil chemotaxin interleukin-8 are elevated in severe acute alcoholic hepati-tis, and tissue levels correlate with neutrophil infiltration. Hepatology 18, 41–46.
Situnayake, R. D., Crump, B. J., Thurnham, D. I., Davies, J. A., Gearty, J., & Davis, M. (1990). Lipid peroxidation and hepatic antioxidants in al-coholic liver disease. Gut31, 1311–1317.
Su, G. L., Klein, R. D., Aminlari, A., Zhang, H. Y., Steinstraeeser, L., Alarcon, W. H., Remick, D. G., & Wang, S. C. (2000). Kupffer cell ac-tivation by lipopolysaccharide in rats: role for lipopolysaccharide bind-ing protein and toll-like receptor 4. Hepatology 31, 932–936.
Su, G. L., Rahemtulla, A., Thomas, P., Klein, R. D., Wang, S. C., & Nanji,
A. A. (1998). CD14 and lipopolysaccharide binding protein expression
in a rat model of alcoholic liver disease. Am J Pathol 152, 841–849. Suto, G., Kiraly, A., & Tache, Y. (1994). Interleukin-1? inhibits gastric emptying in rats: mediation through prostaglandin and corticotropin-releasing factor. Gastroenterology 106, 1568–1575.
Szabo, G., Mandrekar, P., Girouard, L., & Catalano, D. (1996). Regulation of human monocyte functions by acute ethanol treatment: decreased tu-mor necrosis factor-alpha, interleukin-1beta, and elevated interleukin-10, and transforming growth factor-beta production. Alcohol Clin Exp Res20, 900–907.
Thanos, D., & Maniatis, T. (1995). NF-?B: a lesson in family values. Cell 80, 529–532.
Tran-Thi, T.-A., Decker, K., & Baeuerle, P. A. (1995). Differential activa-tion of transcription factors NF-?B and AP-1 in rat liver macrophages.
Hepatology22, 613–619.
Uesugi, T., Froh, M., Arteel, G. E., Bradford, B. U., & Thurman, R. G.
(2001). Toll-like receptor 4 is involved in the mechanism of early alco-hol-induced liver injury in mice. Hepatology 34, 101–108.
Wurfel, M. M., Monks, B. G., Ingalls, R. R., Dedrick, R. L., Delude, R.,
C.J. McClain et al. / Alcohol 27 (2002) 53–6161
Zhou, D., Lamping, N., Schumann, R. R., Thieringer, R., Fenton, M. J., Wright, S. D., & Golenbock, D. (1997). Targeted deletion of the li-popolysaccharide (LPS)-binding protein gene leads to profound sup-pression of LPS responses ex vivo, whereas in vivo responses remain intact. J Exp Med186, 2051–2056.
Yin, M., Bradford, B. U., Wheeler, M. D., Uesugi, T., Froh, M., Goyert,
S. M., & Thurman, R. G. (2001). Reduced early alcohol-induced liver injury in CD14-deficient mice. J Immunol166, 4737–4742.
Zhang, Z., Bagby, G. J., Stoltz, D., Oliver, P., Schwarzenberger, P. O., & Kolls, J. K. (2001). Prolonged ethanol treatment enhances lipopolysaccha-ride/phorbol myristate acetate–induced tumor necrosis factor-alpha pro-duction in human monocytic cells. Alcohol Clin Exp Res25, 444–449.
期末检测题 时间：60分钟分值：100分 一、单项选择题（每小题2分，共20小题，40分） 1.毛泽东在《贺新郎?读史》中吟道：“人猿相揖别。只几个石头磨过，小儿时节。”对“人猿相揖别。只几个石头磨过”理解最为准确的是（） A.人与猿只在一起磨过几个石头后就告别了 B.人和猿在几个磨过的石头边告别了 C.人和动物的根本区别在于是否会制造工具 D.人和动物的根本区别在于是否会磨几个石头 2.小明来到周口店龙骨山，他可以了解到生活在距今约的北京人（） A.80万~30万年 B.70万~30万年 C.70万~20万年 D.80万~20万年 3.右图是某同学在旅游时拍摄的。图中所涉及历史人物的 主要事迹不包括（） A.建立我国第一个王朝 B.因治水有功，舜年老时推举他做了部落联盟首领 C.为治理洪水，三过家门而不入 D.通过禅让制推举启为继承者 4.下面代表了商朝青铜器典型风格的巨鼎是（） A.司母戊鼎 B.青铜立人 C.青铜神树 D.四羊方尊 5.“齐桓公对内整顿朝政，对外‘尊王攘夷’，终于九合诸侯，一匡天下，成就了春秋五霸之首的伟业。”辅佐他成就“五霸之首伟业”的人是（） A.伊尹 B.姜尚 C.管仲 D.勾践 6.春秋战国时期的土地利用率和农作物产量有了显著提高，这主要是因为（） A.农业重视使用肥料 B.青铜器在农业生产中的广泛应用 C.水利工程的兴修 D.铁农具和牛耕的推广 7.“兴，百姓苦；亡，百姓苦。”兴亡之间，战乱不断。在战乱之中，中国涌现出许多杰出的军事家，即便是他们，也把“不战而屈人之兵”作为最高的追求。被称为我国兵家鼻祖的人是（） A.孔子 B.孙膑 C.韩非 D.孙武 8.关于陈胜吴广起义，下列说法有误的是（） A.曾在陈建立政权 B.推翻了秦朝 C.在大泽乡起义 D.是中国历史上的第一次农民大起义 9.近几十年来，我国新疆地区陆续出土了许多汉代的丝织品，这主要反映了（） A.西汉时这一地区才开始出现丝织品 B.丝绸之路开通后，新疆地区与中原地区交往日益密切 C.西汉的丝织品质优价廉 D.汉代新疆人主要穿丝绸衣服 10.史书记载，某事件发生后，“边城晏闭，牛马布野，三世亡（无）犬吠之警，黎庶亡（无）干戈之役”。“某事件”指的是（） A.霍去病反击匈奴 B.昭君出塞
第一章 有理数 1.1 正数和负数 1.B 2.C 3.B 4.输1场 5.从Q 出发后退4下 6. 227，2.7183,2020,480 －18，－0.333…，－259 0 1.2 有理数 1.2.1 有理数 1.C 2.C 3.D 4.0,1 ＋1 3 －0.3,0，－3.3 5.正整数集合：{＋4,13，…}；负整数集合：{－7，－80，…}； 正分数集合：{3.85，…}；负分数集合：{－5 4，－49%，－4.95，…}； 非负有理数集合：{＋4,0,3.85,13，…}； 非正有理数集合：{－7,0，－80，－5 4 ，－49%，－4.95，…}. 1.2.2 数 轴 1.C 2.D 3.B 4.－2或0 5.－1,0,1,2 6.解：在数轴上表示如下. 1.2.3 相反数 1.B 2.D 3.－1 4.(1)－1 (2)3 (3)2 5.解：(1)－3.5的相反数是3.5.(2)35的相反数是－3 5. (3)0的相反数是0.(4)28的相反数是－28. (5)－2018的相反数是2018. 6.解：如图所示. 1.2.4 绝对值 第1课时 绝对值 1.C 2.B 3.B 4.－3 10
5.解：|7|＝7，????－58＝5 8 ，|5.4|＝5.4，|－3.5|＝3.5，|0|＝0. 6.解：因为|x ＋1|＋|y －2|＝0，且|x ＋1|≥0，|y －2|≥0，所以x ＋1＝0，y －2＝0，所以x ＝－1，y ＝2. 第2课时 有理数的大小比较 1.C 2.B 3.(1)＞ (2)＜ (3)＞ 4.－17 5.解：如图所示： 由数轴可知，它们从小到大排列如下： －6＜－514＜－3 5 ＜0＜1.5＜2. 1.3 有理数的加减法 1.3.1 有理数的加法 第1课时 有理数的加法法则 1.B 2.B 3.B 4.A 5.49.3 6.解：(1)原式＝－26.(2)原式＝－6.(3)原式＝－2019. (4)原式＝0.(5)原式＝4.(6)原式＝－5 9 . 第2课时 有理数加法的运算律及运用 1.D 2.交换 结合 －17 ＋19 2 3.解：(1)原式＝[(－6)＋(－4)]＋(8＋12)＝－10＋20＝10. (2)原式＝????147＋3 7＋??? ?? ???－213＋13＝2＋(－2)＝0. (3)原式＝(0.36＋0.64)＋[(－7.4)＋(－0.6)]＋0.3＝1＋(－8)＋0.3＝－6.7. 4.解：根据题意得55＋77＋(－40)＋(－25)＋10＋(－16)＋27＋(－5)＋25＋10＝(55＋77＋10＋27＋10)＋[(－25)＋25]＋[(－40)＋(－16)＋(－5)]＝179＋(－61)＝118(kg).所以今年小麦的总产量与去年相比是增产的，增产118kg. 1.3.2 有理数的减法
2003-2004学年七年级（上）数学试题 题 号 一二三四五六总分 1~8 9~20 21 22 23 24 25 26 27 28 29 得 分 信你在小学原有的基础上又掌握了许多新的数学知识与能力，变得更加聪明了，更加懂得应用数学来解决实际问题了。现在让我们一起走进考场，仔细思考，认真作答，成功将属于你——数学学习的主人。] 一、精心选一选！（只有一个正确答案，每小题4分，计32分） 1、下面几组数中，不相等的是( ) A、－3和+(－3) B、－5和－(+5) C、－7和－(－7) D、+2和│－2│ 2、平面上有任意三点，过其中两点画直线，共可以画（） A、1条 B、3条 C、1条或3条 D、无数条 3、在数轴上表示a、b两数的点如图所示，则下列判断正确的是（） A、a+b＞0 B、a＋b＜0 C、ab＞0 D、│a│＞│b│ 4、下列图形中，哪一个是正方体的展开图（） 5、2002年11月23—29日在泉州销售8000万元即开型福利彩票（每张面额2元），特等奖100万元，结果中一百万元者有15名，假如你花10元买5张，下列说法正确的是写（） A、中一百万元是必然事件 B、中一百万元是不可能事件 C、中一百万元是可能事件，但可能性很小 D、因为5÷15＝1/3，所以中一百万元的可能性是33.3％ 6、计算（－1）1001÷(－1)2002所得的结果是（） A、1/2 B、－1/2 C、1 D、－1 7、任何一个有理数的平方（） A、一定是正数 B、一定不是负数 C、一定大于它本身 D、一定不大于它的绝对值 8、如图，AOC ∠和BOD ∠都是直角，如果 A C B O D
配套中学教材全解工具版 九年级物理上 It was last revised on January 2, 2021
第十三、十四章中考典题补充 1.（2015天津中考）图1为四冲程汽油机工作过程中的某 图1 冲程示意图，该冲程为（） A.吸气冲程 B.压缩冲程 C.做功冲程 D.排气冲程 解析：由图知，两个气门都关闭，火花塞产生电火花，活塞向下运动，因此是做功冲程，故Ｃ选项正确。 答案：C 2. (2015山东泰安中考)四冲程内燃机工作时，哪个冲程将机械能转化为内能( ) A.压缩冲程 B.做功冲程 C.吸气冲程 D.排气冲程 解析：内燃机是将内能转化为机械能的机器，它的一个工作循环包括：吸气、压缩、做功、排气四个冲程，其中压缩冲程是将机械能转化为内能；做功冲程是将内能转化为机械能，故A选项正确。 答案：A 3. (2015?湖北宜昌中考)为节约能源，需要提高热机的效率，下列措施中不能提高热 机效率的是( ) A.尽量使燃料充分燃烧 B.尽量减少热机部件间的摩擦 C.尽量减少废气带走的热量 D.尽量增加热机的工作时间
解析：提高热机效率具有重要的经济效益和社会效益，在物理学中，提高热机效率就是增加有用功或减少额外功。在热机中，使燃料充分燃烧可以提高热机效率；减少废气带走的热量可以提高热机效率；减少热机部件间的摩擦也可以提高热机效率；增加热机的工作时间不能提高热机效率。 答案：D 4. (2013四川自贡中考)如图2所示流程是用来说明单缸四冲程汽油机的一个工作循 环及涉及的主要能量转化情况。对图中①②③④的补充正确的是( ) 图2 A.①做功冲程②内能转化为机械能③压缩冲程④机械能转化为内能 B.①压缩冲程②内能转化为机械能③做功冲程④机械能转化为内能 C.①压缩冲程②机械能转化为内能③做功冲程④内能转化为机械能 D.①做功冲程②机械能转化为内能③压缩冲程④内能转化为机械能 解析：压缩冲程中，活塞压缩汽缸内的气体，使气体内能增大，将机械能转化为内能；做功冲程中，燃料燃烧产生高温高压的燃气推动活塞运动，将内能转化为机械能。所以C选项正确。 答案：C 5. (2013山东济宁中考)我国研制的“神舟九号”试验飞船在返回地面通过大气层的飞 行中，下列说法中不正确的是( ) A.飞船的机械能保持不变 B.飞船的一部分机械能转化为内能 C.飞船的重力势能越来越小 D.飞船的外表温度会升高
初一数学上册试卷及答 案 -CAL-FENGHAI.-(YICAI)-Company One1
七年级数学期中调考试卷 一、选一选，比比谁细心（本大题共12小题，每小题3分，共36分，在每小题 给出的四个选项中，只有一项是符合题目要求的） 1．12 -的绝对值是（ ）． (A) 12 (B)12 - (C)2 (D) -2 2．武汉长江二桥是世界上第一座弧线形钢塔斜拉桥，该桥全长16800m ，用科学记数法表示这个数为（ ）. (A)1.68×104m (B)16.8×103 m (C)0.168×104m (D)1.68×103m 3．如果收入15元记作+15元，那么支出20元记作（ ）元. (A)+5 (B)+20 (C)-5 (D)-20 4．有理数2(1)-，3(1)-，21-, 1-，-(-1)，1 1 --中，其中等于1的个数是 （ ）. (A)3个 (B)4个 (C)5个 (D)6 个 5．已知p 与q 互为相反数，且p ≠0，那么下列关系式正确的是（ ）． (A).1p q = (B) 1q p = (C) 0p q += (D) 0p q -= 6．方程5-3x=8的解是（ ）． （A ）x=1 （B ）x=-1 （C ）x=133 （D ）x=-133 7．下列变形中, 不正确的是（ ）. (A) a ＋(b ＋c －d)＝a ＋b ＋c －d (B) a －(b －c ＋d)＝a －b ＋c －d (C) a －b －(c －d)＝a －b －c －d (D) a ＋b －(－c －d)＝a ＋b ＋c ＋d
8．如图,若数轴上的两点A 、B 表示的数分别为a 、b ，则下列结论正确的是（ ）． (A) b －a>0(B) a －b>0(C) ab ＞0(D) a ＋b>0 9．按括号内的要求，用四舍五入法，对1022.0099取近似值是（ ）. (A)1022.01(精确到0.01) (B)1.0×103(保留2个有效数字) (C)1020(精确到十位) (D)1022.010(精确到千分位) 10．“一个数比它的相反数大-4”，若设这数是x ，则可列出关于x 的方程为 （ ）. (A)x=-x+4 (B)x=-x+（-4） (C)x=-x-（-4） (D)x-（-x ）=4 11. 下列等式变形：①若a b =，则a b x x =；②若a b x x =，则a b =；③若47a b =， 则74 a b =；④若74 a b =，则47a b =.其中一定正确的个数是（ ）. (A)1个 (B)2个 (C)3个 (D)4个 12.已知a 、b 互为相反数，c 、d 互为倒数，x 等于-4的2次方，则式子 1 ()2 cd a b x x ---的值为（ ）． (A)2 (B)4 (C)-8 (D)8 二、填一填, 看看谁仔细(本大题共4小题, 每小题3分, 共12分, 请将你的答案写 在“_______”处) 13．写出一个比12 -小的整数： . 14．已知甲地的海拔高度是300m ，乙地的海拔高度是－50m ，那么甲地比乙地高____________m ． 15．十一国庆节期间，吴家山某眼镜店开展优 惠学生配镜的活动，某款式眼镜的广告如图，请你 为广告牌补上原价． 16．小方利用计算机设计了一个计算程序，输入和输出的数据如下表：
Module 5 Cartoons 检测题 (时间：60分钟；满分：100分) 一、听力部分（15分） （一）听句子，选择正确的答语。（每个句子读一遍） 1.A.Yes, I do. B.Yes, I can. C.Not yet, but I am going to see it next Sunday. 2.A.Sorry, sir, I won’t. B.Yes, I will. C.Yes, I won’t. 3.A.In the classroom. B.With my friends. C.Five years ago. 4.A.Congratulations! B.Sorry to hear that. C.See you later. 5.A.He came two weeks ago. B.Very well. We are both football fans. C.He works very hard. （二）听对话，判断正（T）误（F）。（对话读两遍） 6.Ted has been to America twice. 7. Ted has never been to America. 8.Ted thinks Hollywood is the best place to visit. 9.Washington DC is beautiful but crowded. 10.New York is the best place for a holiday. （三）听短文及短文后的问题，选择正确的答案。（短文及问题读两遍） 11.A.London Park. B.Weston Park. C.Hoar Park. 12.A.Five miles. B.Two miles. C.Three miles. 13.A.In 1671. B.In 1871. C.In 1971. 14.A.10, 000. B.About 1, 000. C.100. 15.A.The best one. B.The better one. C.The good one. 二、单项填空（15分） 16.There are some cartoon ________,such as the Monkey King, Nemo and Shrek. A.character B.favourite C.writers D.favourites 17.It’s against the law for him to rush into ________ house without permission. A.my own private B.him own private C.his own D.own his private 18.Can you help her? She’s ________ deep trouble. A.in B.on C.at D.with 19.There are some trees on ________ sides of the river. A.either B.all C.every D.both 20.About 200 ________ have been sold. https://www.doczj.com/doc/cc2915825.html,lion copy https://www.doczj.com/doc/cc2915825.html,lions copies https://www.doczj.com/doc/cc2915825.html,lions copy https://www.doczj.com/doc/cc2915825.html,lion copies 21.She couldn’t help _______ when she heard the bad news. A.cry B.crying
初一上册数学第一单元试卷及答案 一、仔细选一选(30分) 1. 0是( ) A.正有理数 B.负有理数 C.整数 D.负整数 2. 中国第一座跨海大桥——杭州湾跨海大桥全长36千米，其中36属于( ) A.计数 B.测量 C.标号或排序 D.以上都不是 3. 下列说法不正确的是( ) A.0既不是正数，也不是负数 B.0的绝对值是0 C.一个有理数不是整数就是分数 D.1是绝对值最小的数 4. 在数- , 0 , 4.5, |-9|, -6.79中,属于正数的有( )个 A.2 B.3 C.4 D.5 5. 一个数的相反数是3，那么这个数是( ) A.3 B.-3 C. D. 6. 下列式子正确的是( ) A.2>0>-4>-1 B.-4>-1>2>0 C.-4<-1<0<2 D.0<2>-1<-4 7. 一个数的相反数是最大的负整数，则这个数是( ) A.1 B.±1 C.0 D.-1 8. 把数轴上表示数2的点移动3个单位后，表示的数为( ) A.5 B.1 C.5或1 D.5或-1 9. 大于-2.2的最小整数是( ) A.-2 B.-3 C.-1 D.0 10. 学校、家、书店依次座落在一条东西走向的大街上，学校在家的西边20米，书店在家东边100米,张明同学从家里出发，向东走了50米，接着又向西走了70米，此时张明的位置在( ) A. 在家 B. 在学校 C. 在书店 D. 不在上述地方 二、认真填一填(本题共30分) 11.若上升15米记作+15米，则-8米表示。 12.举出一个既是负数又是整数的数。 13.计算：__________。 14.计算5.24÷6.55，结果用分数表示是______;用小数表示是________。
《中学教材全解》2012-2013学年七年级地理下（湖南教育版）期中检测题.doc 七年级地理（下）期中检测题 本检测题满分100分，时间60分钟 一、选择题（每小题2分，共60分） 1.亚洲是我们共同的“家”，关于这个“家”的“左邻右舍”，说法正确的是( ) A.东邻欧洲，西濒太平洋 B.南望大洋洲，北濒北冰洋 C.东邻北美洲，西濒大西洋 D.西南隔海与北美洲相望，东北隔海与非洲相望 2.亚洲地势的特点是( ) A.以高原为主 B.地面起伏很大，中部地势高，四周地势较为低平 C.以平原为主 D.西部是山地，中部是平原，东部是高原 3.下列地理事物既是亚洲之最也是世界之最的是( ) A.最长的河流——长江 B.面积最大的国家——中国 C.最大的平原——西西伯利亚平原 D.最深的湖泊——贝加尔湖
4.亚洲是世界上( ) A.平均海拔最低的大洲 B.跨经度最广的大洲 C.面积最大的大洲 D.面积最小的大洲 5.下列对亚洲气候特点的叙述，不正确的是( ) A.气候类型复杂多样 B.季风气候显著 C.温带大陆性气候分布面积最广 D.受海洋影响明显 6.下列各地区的区域文化与当地自然条件组合正确的是( ) A.东南亚人多居住长屋——多地震 B.贝都因人居住帐篷——气候湿润、水草丰美 C.孟加拉人以船为交通工具——气候湿热、河网密布 D.也门的住房大多是平顶——气候湿热 7.造成亚洲大陆气候复杂、南北温差大、东西降水差异大的主要原因是( ) ①纬度因素②海陆因素③洋流因素④地形因素 A.②③ B.①④ C.③④ D.①② 8.南美洲的地形特征是（） A.中间高，四周低 B.高原大陆 C.南北三大纵列带 D.西部是山地，东部高原、平原相间分布[来源:学科网]
期末检测题 （本检测题满分：120分，时间：120分钟） 一、选择题（每小题3分，共36分） 1.的相反数和绝对值分别是（ ） A. B. C. D. 2.如果和互为相反数，且 ，那么的倒数是（ ） A.b 21- B.b 21 C.b 2- D. 3.(2020·湖南长沙中考)下列各图中，∠1与∠2互为余角的是( ) A B C D 4.(2020·北京中考改编)有理数a ，b 在数轴上的对应点的位置如图所示，则正确的结论 是( ) A.a >-2 B.a <-3 C.a >-b D.a <-b 5.已知有一整式与的和为，则此整式为（ ） A. B. C. D. 6.(2020·吉林中考)小红要购买珠子串成一条手链.黑色珠子每个a 元,白色珠子每个b 元,要串成如图所示的手链,小红购买珠子应该花费( ) A.(3a +4b )元 B.(4a +3b )元 a +b )元 D.3(a +b )元 第6题图 7.（2020·河北中考）图中的三视图所对应的几何体是（ ） C. D. 第7题图
8.（2020·吉林中考）如图，有一个正方体纸巾盒，它的平面展开图是( ) 第8题图 9.2条直线最多有1个交点，3条直线最多有3个交点，4条直线最多有6个交点，…,那么6条直线最多有（ ） A.21个交点 B.18个交点 C.15个交点 D.10个交点 10.如图，直线 和 相交于点， 是直角， 平分 ， ，则 的大小为（ ） A. B. C. D. 第11题图 11.（2020?山东泰安中考）如图，AB ∥CD ，∠1=58°，FG 平分∠EFD ，则∠FGB 的度数等于（ ） A.122° B.151° C.116° D.97° 12. (2020·山西中考)如图，直线a ∥b ，一块含60°角的直角三角板ABC (∠A ＝60°)按如图所示放置.若∠1＝55°，则∠2的度数为( ) A.105° B.110° C.115° D.120° 二、填空题（每小题3分，共24分） 13.如果 的值与 的值互为相反数，那么等于_____. 14.足球比赛的记分规则是：胜一场得3分，平一场得1分，负一场得0分．一队打14场，负5场，共得19分，那么这个队共胜了_____场. 第11题图 第12题图
一元一次方程应用题知能点1：市场经济、打折销售问题 （1）商品利润＝商品售价－商品成本价（2）商品利润率＝ 商品利润 商品成本价 ×100% （3）商品销售额＝商品销售价×商品销售量（4）商品的销售利润＝（销售价－成本价）×销售量（5）商品打几折出售，就是按原价的百分之几十出售，如商品打8折出售，即按原价的80%出售．1. 某商店开张，为了吸引顾客，所有商品一律按八折优惠出售，已知某种皮鞋进价60元一双，八折出售后商家获利润率为40%，问这种皮鞋标价是多少元？优惠价是多少元？ 2. 一家商店将某种服装按进价提高40%后标价，又以8折优惠卖出，结果每件仍获利15元，这种服装每件的进价是多少？ 3.一家商店将一种自行车按进价提高45%后标价，又以八折优惠卖出，结果每辆仍获利50元，这种自行车每辆的进价是多少元？若设这种自行车每辆的进价是x元，那么所列方程为（） A.45%×（1+80%）x-x=50 B. 80%×（1+45%）x - x = 50 C. x-80%×（1+45%）x = 50 D.80%×（1-45%）x - x = 50 4．某商品的进价为800元，出售时标价为1200元，后来由于该商品积压，商店准备打折出售，但要保持利润率不低于5%，则至多打几折． 5．一家商店将某种型号的彩电先按原售价提高40%，然后在广告中写上“大酬宾，八折优惠”．经顾客投拆后，拆法部门按已得非法收入的10倍处以每台2700元的罚款，求每台彩电的原售价． 知能点2：方案选择问题 6．某蔬菜公司的一种绿色蔬菜，若在市场上直接销售，每吨利润为1000元，?经粗加工后销售，每吨利润可达4500元，经精加工后销售，每吨利润涨至7500元，当地一家公司收购这种蔬菜140吨，该公司的加工生产能力是：如果对蔬菜进行精加工，每天可加工16吨，如果进行精加工，每天可加工6吨，?但两种加工方式不能同时进行，受季度等条件限制，公司必须在15天将这批蔬菜全部销售或加工完毕，为此公司研制了三种可行方案： 方案一：将蔬菜全部进行粗加工． 方案二：尽可能多地对蔬菜进行粗加工，没来得及进行加工的蔬菜，?在市场上直接销售． 方案三：将部分蔬菜进行精加工，其余蔬菜进行粗加工，并恰好15天完成． 你认为哪种方案获利最多？为什么？ 7．某市移动通讯公司开设了两种通讯业务：“全球通”使用者先缴50?元月基础费，然后每通话1分钟，再付电话费0.2元；“神州行”不缴月基础费，每通话1?分钟需付话费0.4元（这里均指市内电话）．若一个月内通话x分钟，两种通话方式的费用分别为y1元和y2元． （1）写出y1，y2与x之间的函数关系式（即等式）． （2）一个月内通话多少分钟，两种通话方式的费用相同？ （3）若某人预计一个月内使用话费120元，则应选择哪一种通话方式较合算？
期末检测题 （时间：120分钟，满分：120分） 一、选择题（每小题3分，共36分） 1.下列运算中，错误的有（ ） ①12 5 1144251 =； ②4)4(2±=-； ③2222 2-=-=-； ④ 20 9 5141251161=+=+. A.1个 B.2个 C.3个 D.4个 2.如图是用4个相同的小矩形与1个小正方形密铺而成的正方形图案，已知该图案的面积为 ，小正方形的面积为，若用表示小矩形的两边长，请观察图案，指出以 下关系式中不正确的是（ ） A. B. C. D. 3.已知，且 ，则（ ） A. B. C. D. 4.若不等式)(3 1 2x m m -> -的解集为，则的值为（ ） A.32 B.12 C.2 D.4 5.不论 为什么实数，代数式 的值（ ） A.总不小于2 B.总不小于7 C.可为任何实数 D.可能为负数 6.两码头相距千米，一船顺水航行需小时，逆水航行需小时，那么水流速度为（ ） A. b s a s 22- B.a s b s 22- C.b a ab -2 D.a b ab -2 7.设一项工程的工程量为1，甲单独做需要天完成，乙单独做需要天完成，则甲、乙两人合做一天的工作量为（ ） A. B. 1a b + C.2a b + D.11 a b +
8.某工地调来人挖土和运土,已知人挖出的土人恰好能全部运走,怎样调配劳动力使挖 出的土能及时运走且不窝工，解决此问题可设派人挖土,其他人运土，列方程: ① ,② 3x ,③7213x x -=, ④372x x =-. 上述所列方程正确的有( ) A.1个 B.2个 C.3个 D.4个 9.如果与 互补，与 互余，则 与 的关系是（ ） A. B. C. D.以上都不对 10.如图，已知直线和 相交于点， 是直角， 平分，， 则的大小为（ ） A. B. C. D. 11.如图，直线相交于点， ∥ ．若 ，则∠ 等于（ ） A.70° B.80° C.90° D.110° 12.如图， ∥ ， 和相交于点，，，则∠等于（ ） A.40° B.65° C.75° D.115°
初中物理学习材料 鼎尚图文制作整理 奇异的容器 能不能制造出这样一种容器，使流出的水不顾容器里面液体的液面在逐渐降低，始终流出得很均匀而不会越来越慢呢？也许你会认为这是办不到的。 但是这是完全可以办到的。如下图所画的瓶正是这样一种奇异的容器。这个容器是一个普通的窄颈瓶，通过它的塞子，插着一根玻璃管。如果你把比玻璃管下端更低的龙头打 开，液体就会均匀地往外流，一直到容器里的液面降低到跟玻璃管下端相平为止。如果把玻璃管插到差不多与水龙头平齐的地方，你就可以使全部液体均匀地从容器里流出，虽然这是 一股很弱的水流。 这是什么缘故呢？让我们想一想，在龙头开着的时候（如图所示），容器里会发生些 什么情况？水向外流的时候，容器里的液面就会下降，外面的空气就通过玻璃管从水下面流进瓶里的稀薄空气里。气泡一个一个从水里冒上来，聚集在容器上部的水面上。这时候在那么高的水平面上所受的压力等于大气的压力。也就是说，从龙头流出的水，只是在 那一层水的压力下往外流，因为容器内外的大气压力是可以相互抵消的。也因为那一层水的高度是不变的，所以从龙头流出的水始终保持着同样的速度，是一点也不奇怪的。 现在请你回答一个问题：如果拔去跟玻璃管下端相平的塞子，那么水会流出得多快 呢？
原来水完全不往外流（当然这只是在孔非常小，可以不予计算的时候才是这样。不然的话，水会在同孔的宽度一样厚的那一薄层水的压力下向外流）。事实上，这里的内外压力都跟大气压力相等，没有什么力能够迫使水向外流。 可是如果你把那个比玻璃管下端高的塞子拔出来，那就不但没有水从容器里流出，外面的空气还会从这里流进容器里。为什么？原因很简单：在容器这一部分里，空气的压力比外面的大气压力要小。 有这种特别性质的容器是物理学家马里奥特发明出来的，所以这样的容器就叫做“马里奥特容器”。 静脉滴注中的压强知识 1．当输液针刚插入瓶内时，有时为何会有药液冲出？ 当护士用针筒把药剂压入瓶子内时，里面空气体积变小，瓶内空气压强增大，因 ，所以当输液针头插入瓶口时，就有药液被压出来，速度很快，直至。这样一来造成了不少药液的损失，有经验的护士总是在压入药剂后抽出一部分空气，使。 2．输液瓶口为何要插两根管？ 假设刚开始时瓶内空气压强等于大气压，瓶口处的压强为，（如图所示）由于一标准大气压能支持高水柱，所以。当输液针插入瓶口后，因，所以有一部分药液经输液管流出。在药液高度降低时，瓶内空气体积变大压强变小，减小，当时，药
七年级上册数学书答案(人教版) 七年级上册数学书答案(人教版) . ┏───────优先看───┓ ╭╮ . ┊ 只有作业题! ┊ ╭╯ . ┊ 好学生专属领地┊ 。声明:本答案不一定正确! . ┗───┰─────┰───┛ 第一章 ①计数:8、100测量:36、100标号:2008、5、1 ②B 种 ③(1) 98294=?(2)34394=?(3)3 8694=? ④<%)(%)(=-?+? 有变化了,便宜了⑤(1)元 (2)25元 ①(1)-200(2)运出吨运入吨(3)转盘沿顺时针方向转了6圈(4) -3m 0m ②正整数:15 ,+69负整数:-21正分数: 65,,+,+74,负分数:,-13 12正有理数:15,65,,+,+69,+74,负有理数:,-13 12,-21 ③自然数:1,2负整数:-1,-2正分数:21负分数:-21,-31 ④(1)收入512元支出4200元收入1200元 (2)805是甲店的收入 -150是甲店的输出(3)一周下来的结余 ③3 4 -a -34 ⑤是数是2 ④ ①丨-1丨=1 丨-12丨=12 丨0丨=0 丨丨= 丨437 丨=437 ②30 6 1 ③错对对 ④正数或0 负数或0 ⑤第一次是12第二次是4第三次是8 实际意义:这辆车总共行驶了24km ②〈〈〉〈〉 ③错对对 小结:
正整数负整数正分数负分数原点单位长度正方向互为相反数 0 两侧原点距离它本身它的相反数 0 大 0 0和正数负数大大 目标与评定: ①1.门牌号码2.邮政编码 ②小数:分数:5 3 ③长:15m 宽:7m 7÷15= 157 ④ 选择3 ⑥0 0 9 1 ⑨-100〈 12 5137〈-- ⑩-4,-3,-2,-1,0,1,2,3,4 ?(1)S=-1 (2)答:S 是正负数,Q 的绝对值最大,因为:它距离S 最远 ? -2 0 2 4 12 14 16 ?直径是是合格的是不合格的 第二章 ①-4 12 8 8 -14 -6 -6℃ ②5 -7 -3 0 ③ 0 -71 -6 1 34 ④(-150)+(+2060)=1910元 ⑤(-56)+(80)=24℃ ⑥小明在银行中存了200元,记为+200元,那他在银行中取100元,记为-100,现在还有多少 ①2 -2 -14 ② -2 11 ③收入元 ④330kg ⑤(1)(-1)+(-2)+(-8)=-11 (2)(-1)+(-2)+3=0 ①3 13 -3 -13 4 -4 ②8 3 -6 11 0 ③-2 -5 -9 -12 -17
第十三、十四章中考典题补充 1. 2.（2015?天津中考）图1为四冲程汽油机工作过程中的某冲程示意 图，该冲程为（） 蚁图1 A.吸气冲程 B.压缩冲程 C.做功冲程 D.排气冲程 解析：由图知，两个气门都关闭，火花塞产生电火花，活塞向下运动，因此是做功冲程，故Ｃ选项正确。 答案：C 2. (2015?山东泰安中考)四冲程内燃机工作时，哪个冲程将机械能转化为内能( ) A.压缩冲程 B.做功冲程 C.吸气冲程 D.排气冲程 解析：内燃机是将内能转化为机械能的机器，它的一个工作循环包括：吸气、压缩、做功、排气四个冲程，其中压缩冲程是将机械能转化为内能；做功冲程是将内能转化为机械能，故A选项正确。 答案：A 3. (2015?湖北宜昌中考)为节约能源，需要提高热机的效率，下列措施中不能提高热机效 率的是( ) A.尽量使燃料充分燃烧 B.尽量减少热机部件间的摩擦 C.尽量减少废气带走的热量 D.尽量增加热机的工作时间 解析：提高热机效率具有重要的经济效益和社会效益，在物理学中，提高热机效率就是增加有用功或减少额外功。在热机中，使燃料充分燃烧可以提高热机效率；减少废气带走的热量可以提高热机效率；减少热机部件间的摩擦也可以提高热机效率；增加热机的工作时间不能提高热机效率。
答案：D 4. (2013?四川自贡中考)如图2所示流程是用来说明单缸四冲程汽油机的一个工作循环及 涉及的主要能量转化情况。对图中①②③④的补充正确的是( ) 图2 A.①做功冲程②内能转化为机械能③压缩冲程④机械能转化为内能 B.①压缩冲程②内能转化为机械能③做功冲程④机械能转化为内能 C.①压缩冲程②机械能转化为内能③做功冲程④内能转化为机械能 D.①做功冲程②机械能转化为内能③压缩冲程④内能转化为机械能 解析：压缩冲程中，活塞压缩汽缸内的气体，使气体内能增大，将机械能转化为内能； 做功冲程中，燃料燃烧产生高温高压的燃气推动活塞运动，将内能转化为机械能。所以C选项正确。 答案：C 5. (2013?山东济宁中考)我国研制的“神舟九号”试验飞船在返回地面通过大气层的飞行 中，下列说法中不正确的是( ) A.飞船的机械能保持不变 B.飞船的一部分机械能转化为内能 C.飞船的重力势能越来越小 D.飞船的外表温度会升高 解析：飞船在返回地面通过大气层的飞行中，飞船要克服空气的摩擦做功，飞船的一部分机械能转化为内能，飞船的机械能减少，而内能增加，外表温度升高，能量的总量不变，B、D选项正确，A选项不正确；飞船的高度越来越小，因此飞船的重力势能越来越小，C选项正确。 答案：A 6. （2014·甘肃白银中考）如图3所示是四冲程汽油机的两个冲程，甲图显示的是汽油机的冲程，乙图中是能转化为能。 甲乙
七年级数学上册有理数单元测试题1 姓名 得分 一、精心选一选：（每题2分、计18分） 1、a,b,c 三个数在数轴上的位置如图所示，则下列结论中错误的是 （ ） （Ａ）a+b<0 （Ｂ）a+c<0 （Ｃ）a －b>0 （Ｄ）b － 2、若两个有理数的和是正数，那么一定有结论（ ） （A ）两个加数都是正数； （B ）两个加数有一个是正数； （C ）一个加数正数,另一个加数为零； （D ）两个加数不能同为负数 3、654321-+-+-+……+2005－2006的结果不可能是： （ ） A 、奇数 B 、偶数 C 、负数 D 、整数 4、两个非零有理数的和是0，则它们的商为： ( ) A 、0 B 、-1 C 、+1 D 、不能确定 5、有１０００个数排一行，其中任意相邻的三个数中，中间的数等于它前后两数的和，若第一个数和第二个数都是１，则1000个数的和等于（ ） （Ａ）1000 （Ｂ）１ （Ｃ）０ （Ｄ）－１ 6、每天供给地球光和热的太阳与我们的距离非常遥远，它距地球的距离约为15000000千米，将150000000千米用 科学记数法表示为（ ） A ．0.15×910千米 B ．1.5×810千米 C ．15×710千米 D ．1.5×710千米 *7、20032004 )2(3)2(-?+- 的值为（ ）．A ．20032- B ．20032 C ．20042- D ．2004 2 *8、已知数轴上的三点A 、B 、C 分别表示有理数a ，1，1-，那么1+a 表示( )． A ．A 、B 两点的距离 B ．A 、C 两点的距离 C ．A 、B 两点到原点的距离之和 D ． A 、C 两点到原点的距离之和 *9． 3028864215 144321-+-+-+-+-+-+- 等于（ ）． A ．41 B ．41- C ．21 D ．2 1 - 二.填空题：（每题3分、计42分） 1、如果数轴上的点A 对应的数为-1.5，那么与A 点相距3个单位长度的点所对应的有理数为_______。 2、倒数是它本身的数是 ；相反数是它本身的数是 ；绝对值是它本身的数是 。 3、m -的相反数是 ，1m -+的相反数是 ，1m +的相反数是 . 4、已知9,a -=那么a -的相反数是 .；已知9a =-，则a 的相反数是 .
Module 4 Rules and suggestions检测题 (时间：60分钟；满分：100分) 一、听力部分(满分20分) A.听句子，选出与所听句子内容相匹配的图画。每个句子读两遍。(每小题1分，满分5分) 1. A. B. C. 2. A. B. C. 3. A. B. C. 4. A. B. C. 5. A. B. C. B.将听到五段对话，每段对话后有一个小题。请在每小题所给的A、B、C三个选项中选出一个最佳选项。每段对话读两遍。(每小题1分，满分5分) 6. Where are they going to eat their lunch? A. In the park. B. In the restaurant. C. In the office. 7. Why does Mary look so happy? A. Because today is her birthday. B. Because she’s won first prize. C. Because she’s passed the exam. 8. What did Sam do last Sunday? A. Went to the town. B. Visited his dad. C. Cleaned the yard. 9. Where does the conversation probably take place? A. In a library. B. In a post office. C. In a bank.
10. What does the man mean? A. He likes going for a picnic in autumn. B. He won’t go for a picnic in bad weather. C. He wants to go for a picnic with the woman. C.听独白，从A、B、C三个选项中选择符合独白内容的选项，回答问题。独白读两遍。(每小题2分，满分10分) 11. Where is Helen from? A. England. B. America. C. Japan. 12. What subject is Helen interested in? A. Chinese. B. Maths. C. History. 13. When will Helen visit China? A. This June. B. This July. C. This August. 14. How will Helen go to Beijing? A. By plane. B. By ship. C. By train. 15. Why does Helen like New York best? A. Because it’s both big and modern. B. Because it’s both old and beautiful. C. Because it’s both modern and beautiful. 二、笔试部分(满分80分) Ⅰ.根据汉语意思完成句子(每小题1分，满分5分) 16.他们给了我许多建议。 They give me many ________. 17.光比声音传播得快。 Light goes ________ than ________. 18.我记得以前见过她。 I ________ ________ her before. 19.他早早到达是为了能得到个好座位。 He arrived early ________ ________ ________ get a good seat. 20.我每天八点之前入睡。 I ________ ________ before eight every day. Ⅱ.补全对话(每小题1分，满分5分) A: Excuse me, sir. 21 B: Certainly. Go along this street. Turn left into Xingfu Street, and the museum is on your right. A: 22 B: It’s about thirty minutes. A: I see. 23
课时练七年级上册数学答案 【篇一：人教版七年级数学上册《有理数》每课时练习 非常全】 ．如果向南走5米，记作+5米，那么向北走8米应记作 ___________． 2．如果温度上升3℃记作+3℃，那么下降5℃记作 ____________． 3．海拔高度是+1356m，表示________，海拔高度是-254m，表示______． 5．6，2005，，0，-3，+1，，-6.8中，正整数和负分数共有…〖〗 a．3个 b．4个 c．5个 d．6个 6．如果全班某次数学测试的平均成绩为83分，某同学考了85分，记作+2分，得分90分和80分应分别记作 _________________________． 8．如果把+210元表示收入210元，那么-60元表示 ______________． 9．粮食产量增产11％，记作+11％，则减产6％应记作 ______________． 11．如果向西走12米记作+12米，则向东走-120米表示的意义是___． 16．在市场经济中，利润计算公式是：利润＝销售收入－销售成本，小亮利用此公式计算爸爸经营的商店在某一天的利润为-25元，请问：-25元的利润是什么意义？ 18.在下列横线上填上适当的词,使前后构成意义相反的量: (1)收入1300元, _________800元; (2) _________80米,下降64米; (3)向北前进30米, _________ 50米. 1.2有理数练习 一、判断 1﹝﹞ 2﹝﹞ 3﹝﹞ 4﹝﹞﹝﹞ 6﹝﹞ 7 ﹝﹞ 8 ﹝﹞ 9﹝﹞ 二、填空 1、某日，泰山的气温中午12点为5℃，到晚上8点下降了6℃.那 么这天晚上8点的气温为。 2、如果零上28度记作28c，那么零下5度记作 3、若上升10m 记作10m，那么－3m表示 4、比海平面低20m的地方，它的高度记作海拔 三、选择题 5、在－3，－1