Biomedical subjects

N Inagaki

Publications and source records attributed to N Inagaki.

At least 37 records · Page 2Linked to original sources

PubMed2001

Recovery of purification-associated reduction in antigen-induced histamine release from rat peritoneal mast cells.

Immunoglobulin E (IgE)-dependent histamine release from purified rat peritoneal mast cells (PMC) is very low in comparison to that from a non-purified preparation (PEC). The reduced histamine release from PMC is recovered or potentiated by reconstitution with separated non-mast cells (NMC). In the present study, further characterization was undertaken to elucidate the mechanisms involved. Sensitized mast cells were recovered from peritoneal cavities of rats, and purified by density gradient centrifugation with Percoll. Effects of NMC reconstitution, membrane fraction of NMC, NMC incubation supernatant, adhesion molecules and extracellular matrix proteins on IgE-dependent histamine release from PMC were examined. IgE-dependent histamine release was significantly potentiated by NMC reconstitution to PMC. The potentiation was dependent on the concentration of NMC reconstituted and reached a plateau after 30 min incubation. Increasing concentration of PMC did not affect the histamine release. Membrane fraction prepared from NMC also potentiated PMC histamine release in a dose-dependent manner. The potentiation reached a plateau in 5 min. Furthermore, incubation supernatant of NMC potentiated PMC histamine release. Antibodies against intercellular adhesion molecule (ICAM)-1, lymphocyte function-associated antigen (LFA)-1, very late activation antigen (VLA)-1, VLA-4 and VLA-6, and fibronectin did not affect the potentiation of PMC histamine release by NMC reconstitution. Fibronectin, laminin and collagen failed to potentiate PMC histamine release. These results indicate that the membrane component(s) of NMC in the rat peritoneal cavity seems to modulate IgE-dependent histamine release from peritoneal mast cells of rats, and that the active molecule(s) may be released from NMC. Adhesion molecules such as ICAM-1, LFA-1 and VLA are not involved.

Animals↗

PubMed2001

Role of mast cells in antigen-induced airway inflammation and bronchial hyperresponsiveness in rats.

The participation of mast cells in the induction of antigen-induced airway inflammation and bronchial hyperresponsiveness (BHR) to acetylcholine (ACh) was investigated using pharmacological agents and mast cell-deficient rats (Ws/Ws). A significant increase in the number of leukocytes in bronchoalveolar lavage fluid (BALF) and bronchial responsiveness to ACh were observed 24 h after antigen (ovalbumin) challenge in sensitized Brown-Norway (BN) rats. Disodium cromoglycate and terfenadine did not inhibit antigen-induced airway inflammation and BHR in sensitized BN rats. In contrast, cyclosporin A (CyA), FK-506 and prednisolone significantly inhibited antigen-induced airway inflammation and BHR in sensitized BN rats. In addition, disodium cromoglycate, terfenadine and prednisolone, but not CyA and FK-506, inhibited homologous passive cutaneous anaphylaxis in rats. Furthermore, a significant increase in the number of leukocytes in BALF and BHR was also observed in Ws/Ws rats 24 h after inhalation of antigen; however, the magnitude of BHR in Ws/Ws rats was lower than that in the congenic rats. These findings suggest that mast cells play a partial role in the development of antigen-induced BHR in rats and that the induction of BHR is barely suppressed by mast cell stabilizing agents.

Acetylcholine↗

PubMed2001

Drugs for the treatment of allergic diseases.

Many kinds of drugs are used for the treatment of allergic diseases. Glucocorticoids are the most efficacious drugs and widely used for the treatment of allergic diseases. Recently, effectiveness of inhaled glucocorticoids for the treatment of bronchial asthma has been established. Beclomethasone dipropionate and fluticasone propionate, which are degraded easily after absorption, are applied by inhalation. Histamine is one of the most important mediators in allergic reactions and antihistamines have widely been applied for the treatment of allergic skin diseases. In Japan, over 20 antiallergic drugs, such as mediator release inhibitors, mediator antagonists and mediator synthesis inhibitors, have been developed. Recently developed compounds such as pranlukast and suplatast are very effective. To relieve the asthmatic attack, bronchodilators such as beta2-adrenoceptor agonists, theophylline and anti-cholinergic drugs are used. Clinical application of tacrolimus ointment has just started for the treatment of atopic dermatitis. Recently the number of allergic patients has increased. The onset and development of allergic diseases are considered to be dependent on both the genetic factors and the environmental factors. For the successful treatment of patients with allergic diseases, it is also important to consider the control of environmental factors.

Anti-Allergic Agents↗

PubMed2001

VUF-K-8788, a periphery-selective histamine H1 antagonist with anti-pruritic activities.

The pharmacological properties of 7-[3-[4-(2-quinolinylmethyl)-1-piperazinyl]-propoxy]-2,3-dihydro-4H-1,4-benzothiazin-3-one (VUF-K-8788) were investigated in vitro and in vivo. VUF-K-8788 inhibited [3H]-mepyramine from binding to the cell membrane of lung parenchyma (Ki value: 5.0 nM) and the histamine-induced contraction of isolated guinea pig ileum (pA2: 9.71) without affecting ileal contractions induced by acetylcholine, serotonin, KCl and BaCl2. The increase of vascular permeabilities induced by histamine and passive cutaneous anaphylaxis (PCA) in guinea pigs were inhibited by VUF-K-8788 in a dose-dependent fashion (ED50: 0.24 and 0.26 mg/kg, p.o., respectively). Moreover, the anti-histaminic effect of VUF-K-8788 was also observed in rats. In experiments on the effects on the central nervous system, VUF-K-8788 at 1 mg/kg, p.o. hardly antagonized the H1 receptor at all in the cerebral cortex of guinea pigs. VUF-K-8788 inhibited the PCA-induced scratching behavior completely without affecting thiopental-induced sleep in mice. These results suggested that VUF-K-8788 would be useful in the treatment of allergic disorders such as atopic dermatitis and eczema.

Animals↗

PubMed2001

High rate of IgE-mediated histamine release from rat mesenteric mast cells.

IgE-dependent histamine release from rat mesenteric mast cells was investigated. Excised mesenterium was cut into pieces and incubated with IgE overnight at 4 degrees C for sensitization. Over 10 pieces of mesenterium specimen could be prepared from a rat. Antigen-induced histamine release from mesenterium specimen was initiated rapidly and reached a plateau in 5 min. In an optimal condition, over 50% of total histamine was released. In contrast, unpurified and purified peritoneal mast cells released only 22.5% and 5.3% of total histamine, respectively, upon IgE stimulation. Tranilast, a mast cell stabilizer, inhibited the histamine release from mesenteric mast cells significantly. The mesenterium might be useful material for studying tissue-associated mast cell activation.

Animals↗

PubMed2000

Molecular cloning of a novel importin alpha homologue from rice, by which constitutive photomorphogenic 1 (COP1) nuclear localization signal (NLS)-protein is preferentially nuclear imported.

Nuclear import of proteins that contain classical nuclear localization signals (NLS) is initiated by importin alpha, a protein that recognizes and binds to the NLS in the cytoplasm. In this paper, we have cloned a cDNA for a novel importin alpha homologue from rice which is in addition to our previously isolated rice importin alpha1a and alpha2, and we have named it rice importin alpha1b. In vitro binding and nuclear import assays using recombinant importin alpha1b protein demonstrate that rice importin alpha1b functions as a component of the NLS-receptor in plant cells. Analysis of the transcript levels for all three rice importin alpha genes revealed that the genes were not only differentially expressed but that they also responded to dark-adaptation in green leaves. Furthermore, we also show that the COP1 protein bears a bipartite-type NLS and its nuclear import is mediated preferentially by the rice importin alpha1b. These data suggest that each of the different rice importin alpha proteins carry distinct groups of nuclear proteins, such that multiple isoforms of importin alpha contribute to the regulation of plant nuclear protein transport.

Amino Acid Sequence↗

PubMed2000

Overexpression and characterization of carboxyl-terminal processing protease for precursor D1 protein: regulation of enzyme-substrate interaction by molecular environments.

CtpA, which is classified as a novel type of serine protease with a Ser/Lys catalytic dyad, is responsible for the C-terminal processing of precursor D1 protein (pD1) of the photosystem II reaction center, a process that is indispensable for the integration of water-splitting machinery in photosynthesis. In this study, overexpression in Escherichia coli and one-step purification of spinach CtpA were carried out to analyze the characteristics of this new type of protease and to elucidate the molecular interactions in the C-terminal processing of pD1 on the thylakoid membrane. The successful accumulation of functional CtpA in E. coli may argue against the possibility, based on homology to E. coli Tsp, that the enzyme is involved in the degradation of incomplete proteins in chloroplasts, e.g. by utilizing the ssrA-tagging system. Analysis using a synthetic pD1 oligopeptide demonstrated that the enzymatic properties (including substrate recognition) of overexpressed CtpA with an extra sequence of GSHMLE at the N terminus were indistinguishable from those of the native enzyme. CtpA was insensitive to penem, which has been shown to inhibit some Ser/Lys-type proteases, suggesting that the catalytic center of CtpA is quite unique. By using the substrate in different molecular environments (i.e. synthetic pD1 oligopeptide in solution and pD1 in photosystem II-enriched thylakoid membrane), we observed a dramatic difference in the pH profile and affinity for the substrate, suggesting the presence of a specific interaction of CtpA with a factor(s) that modulates the pH dependence of proteolytic action in response to physiological conditions.

Amino Acid Sequence↗

PubMed2000

Cloning, characterization and tissue distribution of the rat ATP-binding cassette (ABC) transporter ABC2/ABCA2.

The ABC1 (ABCA) subfamily of the ATP-binding cassette (ABC) transporter superfamily has a structural feature that distinguishes it from other ABC transporters. Here we report the cloning, molecular characterization and tissue distribution of ABC2/ABCA2, which belongs to the ABC1 subfamily. Rat ABC2 is a protein of 2434 amino acids that has 44.5%, 40.0% and 40.8% identity with mouse ABC1/ABCA1, human ABC3/ABCA3 and human ABCR/ABCA4 respectively. Immunoblot analysis showed that proteins of 260 and 250 kDa were detected in COS-1 cells transfected with ABC2 having a haemagglutinin tag, while no band was detected in mock-transfected cells. After incubation with N-glycosidase F, the mobilities of the two proteins increased and a single band was detected, suggesting that ABC2 is a glycoprotein. Photoaffinity labelling with 8-azido-[alpha-(32)P]ATP confirmed that ATP binds to the ABC2 protein in the presence of Mg(2+). RNA blot analysis showed that ABC2 mRNA is most abundant in rat brain. Examination of brain by in situ hybridization determined that ABC2 is expressed at high levels in the white matter, indicating that it is expressed in the oligodendrocytes. ABC2, therefore, is a glycosylated ABC transporter protein, and may play an especially important role in the brain. In addition, the N-terminal 60-amino-acid sequence of the human ABC1, which was missing from previous reports, has been determined.

ATP-Binding Cassette Transporters↗

PubMed2000

Activation of Ca2+/calmodulin-dependent protein kinase II within post-synaptic dendritic spines of cultured hippocampal neurons.

To understand the cell signaling of protein kinases, it is essential to monitor their activity in each of the subcellular compartments. Here we developed a method to visualize the activities of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in the cytoplasm, plasma membrane, and nucleus, separately, by utilizing targeted phosphorylation motifs and phosphorylation-specific antibodies. This approach was used to monitor the activities of post-synaptic CaMKII in cultured hippocampal neurons. Strong stimulation of the neurons by N-methyl-d-aspartate led to global activations of CaMKII in the cell bodies and dendrites. On the other hand, weak stimulation by removal of Mg(2+) block of N-methyl-d-aspartate receptors induced CaMKII signaling localized within single dendritic spines. Post-synaptic CaMKII is thought to modify synaptic efficiency. The present data for the first time demonstrate the activation of CaMKII localized within single dendritic spines and are consistent with the notion that synaptic efficiency is modified by CaMKII in single or multiple spine level depending on the strength of receptor activation.

Amino Acid Sequence↗

PubMed2000

Roles of mitogen-activated protein kinase pathways for mediator release from human cultured mast cells.

Human cultured mast cells (HCMC) secrete histamine, sulfidoleukotrienes (LTs), and prostaglandin D(2) (PGD(2)), and produce a variety of cytokines after aggregation of high-affinity receptors for IgE (FcepsilonRI). With respect to the mitogen-activated protein kinase (MAPK) family, extracellular signal-regulated kinases (ERKs), c-Jun NH(2)-terminal kinases (JNKs), and p38 mitogen-activated protein kinase (p38 MAPK) are known. To investigate the roles of these kinase pathways for mediator release from human mast cells, we examined the participation of the activation of these kinases in mediator release, using 1,4-diamino-2, 3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126), an ERK pathway inhibitor, and 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imid azo le (SB203580), a p38 MAPK pathway inhibitor. U0126 inhibited ERK activation, LT and PGD(2) release, and granulocyte macrophage-colony stimulating factor (GM-CSF) production after stimulation of HCMC. SB203580, on the other hand, potentiated JNK activation and GM-CSF production. The findings of the present study demonstrated that: (i) the release of arachidonic acid metabolites is mediated by the ERK pathway; (ii) GM-CSF production may be driven by both the ERK and JNK pathways; and (iii) the p38 MAPK pathway negatively regulates the JNK pathway. This suggests that MAPK pathways play important roles in mediator release from human mast cells.

Butadienes↗

PubMed2000

Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways for growth cone collapse.

We previously identified Rho-associated protein kinase (Rho-kinase) as a specific effector of Rho. In this study, we identified collapsin response mediator protein-2 (CRMP-2), as a novel Rho-kinase substrate in the brain. CRMP-2 is a neuronal protein whose expression is up-regulated during development. Rho-kinase phosphorylated CRMP-2 at Thr-555 in vitro. We produced an antibody that specifically recognizes CRMP-2 phosphorylated at Thr-555. Using this antibody, we found that Rho-kinase phosphorylated CRMP-2 downstream of Rho in COS7 cells. Phosphorylation of CRMP-2 was observed in chick dorsal root ganglion neurons during lysophosphatidic acid (LPA)-induced growth cone collapse, whereas the phosphorylation was not detected during semaphorin-3A-induced growth cone collapse. Both LPA-induced CRMP-2 phosphorylation and LPA-induced growth cone collapse were inhibited by Rho-kinase inhibitor HA1077 or Y-32885. LPA-induced growth cone collapse was also blocked by a dominant negative form of Rho-kinase. On the other hand, semaphorin-3A-induced growth cone collapse was not inhibited by a dominant negative form of Rho-kinase. Furthermore, overexpression of a mutant CRMP-2 in which Thr-555 was replaced by Ala significantly inhibited LPA-induced growth cone collapse. These results demonstrate the existence of Rho-kinase-dependent and -independent pathways for growth cone collapse and suggest that CRMP-2 phosphorylation by Rho-kinase is involved in the former pathway.

Amino Acid Sequence↗

PubMed2000

Measurement of glucose uptake and intracellular calcium concentration in single, living pancreatic beta-cells.

There has been no method previously to measure both glucose transport and its effect on the various intracellular functions in single, living mammalian cells. A fluorescent derivative of d-glucose, 2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG), that we have developed has made such measurements possible. COS-1 cells that overexpress the human glucose transporter GLUT2 show significantly greater 2-NBDG uptake than mock transfected cells. Using GLUT2-abundant mouse insulin-secreting clonal MIN6 cells, we found that 2-NBDG was incorporated into the cells in a time- and concentration-dependent manner. The 2-NBDG uptake was inhibited by high concentrations of d-glucose in a dose-dependent manner and also was almost completely inhibited by 10 micrometer cytochalasin B. We then measured both glucose uptake and the intracellular calcium concentration ([Ca(2+)](i)) in single, living pancreatic islet cells. 2-NBDG and fura-2 were used as the tracer of glucose and indicator of intracellular calcium, respectively. All of the cells that showed an increase in [Ca(2+)](i) in response to a high concentration of glucose (16.8 mm) rapidly incorporated significant 2-NBDG. Immunocytochemical examination confirmed these cells to be insulin-positive beta-cells. All of the cells that showed no significant, rapid 2-NBDG uptake lacked such glucose responsiveness of [Ca(2+)](i), indicating that these cells were non-beta-cells such as glucagon-positive alpha-cells. These results show the uptake of glucose causing a concomitant increase of [Ca(2+)](i) in beta-cells. Because 2-NBDG is incorporated into mammalian cells through glucose transporters, it should be useful for the measurement of glucose uptake together with concomitant intracellular activities in many types of single, living mammalian cells.

Animals↗

PubMed2000

Evaluation of anti-scratch properties of oxatomide and epinastine in mice.

Anti-scratch effects of oxatomide and epinastine were examined in mice. Scratching behavior and cutaneous reactions were induced in BALB/c, ICR and ddY mice by dinitrofluorobenzene painting, passive cutaneous anaphylaxis and substance P injection, respectively. Although oxatomide and epinastine failed to inhibit scratching behavior in BALB/c mice, they inhibited the cutaneous reaction significantly. The drugs potently inhibited both scratching behavior and cutaneous reaction in ICR mice. They also inhibited scratching behavior and cutaneous reaction in ddY mice, although cetirizine and terfenadine failed to affect them. Histamine did not induce frequent scratching behavior in BALB/c and ddY mice. These results indicate that oxatomide and epinastine inhibit the scratching behavior in ICR mice associated with passive cutaneous anaphylaxis mainly through an antagonistic action on histamine H(1) receptors. The results also indicate that these drugs inhibit substance P-induced scratching behavior in ddY mice through an action independent of the antagonistic action on histamine H(1) receptors.

Animals↗

PubMed2000

A sealed cranial window system for simultaneous recording of blood flow, and electrical and optical signals in the rat barrel cortex.

We have developed a new sealed cranial window technique which allows the manipulation of simultaneously and independently multiple sensor probes, such as a glass microelectrode and a laser-Doppler probe. possible. Furthermore, normal intracranial pressure (4 mmHg) can be maintained throughout the craniectomy and the experiment. Using this technique, we have measured the neuronal activity and local cerebral blood flow together with the intrinsic optical properties in the rat barrel cortex during mechanical stimulation of the whiskers. The onset of the field response recorded by an extracellular electrode in the principal barrel columns occurred about 8 ms from the beginning of stimulation. These responses were well correlated with the whisker displacements (3 Hz, 2 s). The local cerebral blood flow, measured by laser-Doppler flowmetry, started to increase about 0.5 s after the first field response, peaked at about 1.7 s, and then gradually waned. A similar time-course of changes in the local blood volume was observed by simultaneous intrinsic optical imaging at the hemoglobin-isosbestic wavelength (570 nm). These results suggest that our technique would be useful for assessing the mechanism underlying neurovascular coupling under physiological conditions in vivo.

Animals↗

PubMed2000

Synthesis and biological activities of novel antiallergic agents with 5-lipoxygenase inhibiting action.

Novel benzimidazole derivatives were synthesized and their pharmacological activities were examined. These compounds showed a good suppressive action on histamine release from rat peritoneal mast cells produced by antigen-antibody reaction, an antagonistic action on guinea pig ileum contraction caused by histamine, an inhibitory action on 5-lipoxygenase in rat basophilic leukemia-1 (RBL-1) cells, and a preventive action on NADPH dependent lipid peroxidation induced by Fe3+-ADP in rat liver microsomes. In addition, 1-[2-[2-(4-Hydroxy-2,3,5-trimethylphenoxy)ethoxy]-ethyl]-2-(4-meth yl-1-homopiperazino)-1H-benzimidazole difumarate (BOM1006) exhibited a dose dependent suppressive action on 48 h homologous passive cutaneous anaphylaxis (PCA) reaction in rats orally administered the drug.

Animals↗

PubMed2000

Different role of IL-4 in the onset of hapten-induced contact hypersensitivity in BALB/c and C57BL/6 mice.

1. To study the role of interleukin (IL)-4 in the onset of contact hypersensitivity (CH) in mice, the effect of IL-4 gene-depletion and anti-IL-4 monoclonal antibody treatment on dinitrofluorobenzene (DNFB)-induced CH was examined. Simultaneously, to clarify the effect of background gene, DNFB-induced CH in BALB/c and C57BL/6 mice was compared. 2. Five repeated topical applications of DNFB to the ears of mice resulted in CH of the ears in terms of increases in ear thickness and histopathological changes. The magnitude of ear thickness increase in BALB/c mice was almost three times greater than that in C57BL/6 mice. 3. The CH in BALB/c mice was significantly suppressed by IL-4 gene-depletion and anti-IL-4 monoclonal antibody treatment. In contrast, the symptoms of dermatitis in C57BL/6 mice were slightly affected by the same treatment. These changes corresponded well to the production of specific IgE antibody. 4. Total IgE antibody production and the expression of productive Cepsilon mRNA were dramatically suppressed by IL-4 gene-depletion and anti-IL-4 treatment in BALB/c and C57BL/6 mice. Neither total IgG nor IgM levels in either strain of mice was altered by depletion of IL-4. 5. The expression of IFN-gamma in the skin lesion was dramatically suppressed by IL-4 gene-depletion in BALB/c mice, but not in C57BL/6 mice. 6. These findings indicate that IL-4 plays an important role in the onset of DNFB-induced CH in BALB/c mice, but not in C57BL/6 mice.

Animals↗

PubMed2000

Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells.

BACKGROUND: Flavonoids have a variety of activities including anti-allergic activities, and are known to inhibit histamine release from human basophils and murine mast cells. OBJECTIVE: The effects of luteolin, a flavone, on the immunoglobulin (Ig) E-mediated allergic mediator release from human cultured mast cells (HCMCs) were investigated and compared with those of baicalein and quercetin. METHODS: HCMCs were sensitized with IgE, and then treated with flavonoids before challenge with antihuman IgE. The amount of released mediators was determined as was mobilization of intracellular Ca2+ concentration, protein kinase C (PKC) translocation and phosphorylation of intracellular proteins were detected after anti-IgE stimulation. RESULTS: Luteolin, baicalein and quercetin inhibited the release of histamine, leukotrienes (LTs), prostaglandin D2 (PGD2), and granulocyte macrophage-colony stimulating factor (GM-CSF) from HCMC in a concentration-dependent manner. Additionally, the three flavonoids inhibited A23187-induced histamine release. As concerns Ca2+ signalling, luteolin and quercetin inhibited Ca2+ influx strongly, although baicalein did slightly. With regard to PKC signalling, luteolin and quercetin inhibited PKC translocation and PKC activity strongly, although baicalein did slightly. The suppression of Ca2+ and PKC signallings might contribute to the inhibition of mediator release. The activation of extracellular signal-regulated kinases (ERKs) and c-Jun NH2-terminal kinase (JNK), that were activated just before the release of LTs and PGD2 and GM-CSF mRNA expression in IgE-mediated signal transduction events, were clearly suppressed by luteolin and quercetin. In contrast, the flavonoids did not affect the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway. CONCLUSION: These results indicate that luteolin is a potent inhibitor of human mast cell activation through the inhibition of Ca2+ influx and PKC activation.

Calcium↗

PubMed2000

Effect of a fluorinated pyrimidine on cachexia and tumour growth in murine cachexia models: relationship with a proteolysis inducing factor.

The fluorinated pyrimidine nucleoside, 5'-deoxy-5-fluorouridine (5'-dFUrd) has been shown to effectively attenuate the progress of cachexia in the murine adenocarcinomas MAC16 and colon 26 as well as in the human uterine cervical carcinoma xenograft, Yumoto. Although concomitant inhibition of tumour growth was observed in all three models this was not sufficient to account for the preservation of body weight. An attempt has been made to correlate the anti-cachectic activity of 5'-dFUrd with the presence of a tumour produced proteolysis-inducing factor (PIF), thought to be responsible for the development of cachexia in the MAC16 model. Two variants of colon 26 adenocarcinoma were employed, clone 20 which produces profound cachexia, and clone 5 which produces no change in body weight in recipient animals. Mice bearing the colon 26, clone 20 variant showed evidence for the presence of PIF in tumour, serum and urine, while there was no evidence for the presence of PIF in tumour or body fluids of mice bearing the clone 5 tumours. Treatment of animals bearing the clone 20 variant with 5'-dF Urd led to the disappearance of PIF from the tumour, serum and urine concomitant with the attenuation of the development of cachexia. The human cervical carcinoma, Yumoto, which also induced cachexia in recipiant animals, showed expression of PIF in tumour, serum and urine in control and vehicle-treated mice, but was absent in mice treated with 5'-dFUrd. Thus in these experimental models cachexia appears to be correlated with the presence of PIF.

Adenocarcinoma↗