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1.
An abnormal mucosal cell-mediated immune response plays a fundamental role in the pathogenesis of celiac disease. To characterize locally infiltrating T cells, gliadin-specific T-cell clones were isolated from two treated celiac patients. Mucosal biopsies were cultured in vitro for 24 hr with a peptic-tryptic digest (PT) of gliadin. T-cell clones (TCC) were then isolated by limiting dilution. The production of interferon- (IFN-) and interleukin-4 (IL-4) was evaluated by ELISA in culture supernatants obtained after a short incubation with anti-CD3 and PMA, or with antigen. Twenty-two TCC were specific for gliadin and/or PT. All were CD3+, CD4+, CD8+, TCR +. In one such clone the PT-specific response was inhibited by an anti-DQ, but not by an anti-DR antibody. Of the five gliadin-specific TCC examined, four produced IL-4 and high levels of IFN-; the remaining one initially produced only IL-4, but subsequently also IFN-. All clones obtained from the celiac mucosa, including the gliadin-specific ones, produced high levels of IFN-, in most cases with IL-4. This cytokine profile could explain most of the immunological features of the celiac mucosa.  相似文献   

2.
Purpose Estrogen receptor (ER) is the second identified receptor mediating the effects of estrogen on target tissues. The role of ER in cancer pathobiology is largely unknown, because specific antibodies have not been available until recently. Initial studies have shown that ER expression declines in breast, ovarian, prostatic, and colon carcinomas. Tamoxifen, a synthetic anti-estrogen compound that is a mixed agonist/antagonist of estrogen receptor (ER) and a pure antagonist of ER, has moderate beneficial effects in human astrocytic neoplasms. However, most published studies agree that glial tumors do not express ER. The purpose of this study was to explore the expression of ER in astrocytic neoplasms.Methods ER expression was monitored immunohistochemically in 56 cases of astrocytomas of all grades (grade I–IV) and in adjacent non-neoplastic brain tissue.Results Moderate or strong nuclear immunopositivity was obtained in non-neoplastic astrocytes and in low-grade astrocytomas, whereas the majority of high-grade tumors were immunonegative or displayed weak immunoreactivity. The progressive decline in ER expression paralleled the increase in tumor grade.Conclusions In as much as ER is possibly the only ER expressed in astrocytes, its decreased expression may play an important role in astrocytic tumor initiation and in the potential response of glial neoplasms to tamoxifen.  相似文献   

3.
Summary The effect of macrophages on the uptake of -very low-density lipoprotein (-VLDL) by smooth muscle cells (SMC) expressing different morphological phenotypes was examined in culture. The SMC were grown alone and in co-culture with macrophages for four days, then incubated with different concentrations of125I--VLDL for 3 h at 4°C or with 75 ug/ml -VLDL for 24h at 37°C. The binding of -VLDL to SMC at 4°C was enhanced in the presence of macrophages irrespective of the phenotype expressed by SMC. This occurred through modification of the lipoprotein, since binding of re-isolated macrophage-conditioned -VLDL to SMC was 12.5 times that of fresh -VLDL. This modified form of -VLDL competed with fresh -VLDL for binding to SMC. Binding was inhibited in the presence of probucol, suggesting that an oxidative mechanism may be involved.The presence of macrophages also enhanced the accumulation of -VLDL-derived cholesterol in SMC. While most of this is a consequence of the enhanced binding, macrophages may also act directly on SMC to increase cholesterol accumulation, since the activity of acid cholesterol ester hydrolase and neutral cholesterol ester hydrolase in SMC was reduced in the presence of macrophages.  相似文献   

4.
We studied the time course of the regeneration of the jejunal mucosa of the rat after it was damaged by exposure to the surfactant, benzalkonium chloride. We placed particular emphasis on assessing the morphology of the nerve fibers within the villi during and after regeneration. The application of benzalkonium chloride resulted in virtually complete loss of villi within the treated segment; however, the crypts were only partially damaged. The mucosa began to regenerate within 6 hr of the insult. The villus lengths and crypt depths returned to pretreatment values within two to four days. The mucosal innervation was assessed through immunohistochemistry for vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and neuron-specific enolase (NSE). At all stages of regeneration, VIP, NPY, and NSE immunopositive fibers within the lamina propria extended to the tips of the villi. The density of the immunopositive fibers in the lamina propria at four days after mucosal insult was similar to that in control tissues regardless of the neuronal marker visualized. We conclude that the nerve fibers innervating the small intestinal mucosa grow at a rate of approximately 100 m/day and that the entire length of each villus contains nerve fibers throughout the regeneration process. The innervation of the regenerated mucosa appears identical to that of control mucosa.Norman A. See is a Fellow of the American Foundation for Pharmaceutical Education.Supported by NIH grant AM32594 (P.B.) and NSF grant BNS-8820658 (M.E.).  相似文献   

5.
Transforming growth factor- (TGF-)signal transduction is mediated via specific cellsurface signaling TGF- receptors, most notably thetype I ALK5 (TR-IALK5)and the type II(TR-II). We evaluated TR-IALK5 andTR-II expression in 41 human pancreatic cancertissue samples and correlated these findings withclinical data of the patients. Northern blot analysisindicated that, in comparison with the normal pancreas,pancreatic adenocarcinomas exhibited 8.0-fold and4.5-fold increases (P < 0.01), respectively, in mRNAlevels encoding TR-IALK5 andTR-II. In situ hybridization showed that both TR-IALK5 mRNAwere highly expressed in the majority of pancreaticcancer cells. Immunohistochemical analysis ofTR-IALK5 and TR-II revealedpositive immunostaining in 73% and 56% of the tumors, respectively. Both receptorswere concomitantly present in 54% of the pancreaticcancer samples. The presence ofTR-IALK5 or TR-II and theconcomitant presence of TR-IALK5 and TR-II in the cancer cells was associatedwith advanced tumor stage (P < 0.01). These findingsshow that in many human pancreatic cancers, increasedlevels of the two signaling TRs are present. The presence of the signaling TRs inadvanced tumor stages indicates a role in diseaseprogression.  相似文献   

6.
Zusammenfassung 133 Patienten einer Intensivpflegestation, die bei der Aufnahme keine Symptome bakterieller Infektion zeigten und noch keine Antibiotika erhalten hatten, wurden nach dem Zufallsprinzip zwei Gruppen zugeordnet. Eine Gruppe (+Pat.) erhielt eine Antibiotikaprophylaxe mit Penicillinen oder Cephalosporinen, die zweite Gruppe (–Pat.) erhielt keine Antibiotika. Staph. aureus war bei –Pat. im Trachealsekret und in der Umgebung der häufigste potentiell pathogene Keim. Staph. aureus war im Trachealsekret und in der Umgebung der –Pat. signifikant häufiger als bei +Pat.. Klebsiella spp. standen im Trachealsekret und in der Umgebung von +Pat. an erster Stelle. Sie waren im Trachealsekret von +Pat. signifikant häufiger als bei –Pat.. In der ersten Woche des Stationsaufenthaltes traten bei +Pat. starke Veränderungen in der Keimflora der Trachealsekrete auf: die Besiedelung mit gramnegativen Keimen stieg auf fast 100% an, gleichzeitig ging die Frequenz von Staph. aureus zurück. In den Abklatschuntersuchungen aus der Patientenumgebung traten gramnegative Stäbchen bei +Pat. in signifikant höheren Koloniezahlen auf als bei –Pat.. Die paarweisen Vergleiche von Bakterienstämmen aus den Trachealsekreten und aus der Patientenumgebung ergaben, daß +Pat. gramnegative Keime und –Pat. Staph. aureus signifikant häufiger an die Umgebung abgaben. Auf die Kontamination der Patientenumgebung mit Staph. aureus wirkte sich der Faktor der trachealen Intubation nicht aus. Gramnegative Keime waren im Trachealsekret von intubierten Patienten signifikant häufiger als bei nicht intubierten. Derselbe Trend zeigte sich auch in der Patientenumgebung. Die Antibiotikaprophylaxe konnte, wie die klinischen Ergebnisse der Studie zeigten, die Patienten nicht im erwarteten Ausmaß vor Infektionen schützen. Patienten, insbesondere tracheal-intubierte, die Antibiotika erhalten, sind als Streuquellen für hochresistente gramnegative Keime anzusehen.
The patient as a source of bacteria in intensive care units: Influence of antibiotics and tracheal intubation
Summary 133 patients in an intensive care unit, who prior to admission had not shown any signs of bacterial infection and had not received antibiotic treatment, were assigned to two groups at random. One group received antibiotic prophylaxis with penicillins or cephalosporins (+Pat.), the other group did not receive antibiotics (–Pat.). Staph. aureus was the most frequent facultative pathogen in tracheal secretions and in the environment of –Pat.. This organism was significantly more frequent in –Pat. than in +Pat. in both the tracheal secretions and the enviroment. Klebsiella spp. outnumbered all other species in +Pat.. They were significantly more frequent in tracheal secretions of +Pat. than of –Pat.. In the first week of hospitalisation marked changes were seen in bacterial flora of tracheal secretions of +Pat.. Colonization with gramnegative bacteria rose to nearly 100%, the frequency of Staph. aureus diminishing at the same time. Monitoring by contact cultures revealed that gramnegative rods were significantly more numerous in the environment of +Pat. than of –Pat.. Matching bacterial strains cultured from tracheal secretions and from the environment of the patients proved that +Pat. spread significantly higher numbers of their gramnegative bacteria into the environment. The same is true of –Pat. for Staph. aureus. Intubation had no noticeable effect on the degree of contamination of the surroundings with Staph. aureus. Gramnegative rods were significantly more frequent in tracheal secretions of patients with intubation than in patients without. The same trend was observed for environmental contamination. As the clinical results of this study have shown, antibiotic prophylaxis does not protect patients from infections to the extent expected. Patients, and particularly intubated patients, receiving antibiotic treatment have to be considered as sources of highly resistant gramnegative organisms.
  相似文献   

7.
Summary We have analyzed the levels and composition of the fetal hemoglobin (Hb F) in several members of a Czechoslovakian family with a heterozygosity for a newly discovered -thalassemia (codons 38/39; -C), or for a newly detected nondeletional hereditary persistence of fetal hemoglobin (a form of Swiss-HPFH with an AC mutation at nucleotide –100 5 to the Cap site of G), or with a compound heterozygosity for these two conditions. The Hb F level in the -thalassemia heterozygotes averaged 0.3% with low G values ( 28%) and relatively high AT values ( 50%), that in the two Swiss-HPFH heterozygotes averaged 0.8% with 95% G, while that of the compound heterozygote was 3.1% with 95% G. The low Hb F levels were determined with a recently published cation exchange high-performance liquid chromatography (HPLC) procedure that is accurate at the 0.1%–0.2% Hb F level [3]. This method, together with a reversed-phase HPLC procedure, made it possible to detect this unusual type of nondeletional G-HPFH and provided the data indicating that the increased Hb F in the compound heterozygote was derived mainly from the chromosome with the HPFH determinant.This study was supported in part by USPHS Research Grant HLB-41544  相似文献   

8.
J. J. Holst 《Diabetologia》1977,13(2):159-169
Summary Different techniques for the extraction and initial purification of porcine gastrointestinal glucagon-like immunoreactivity (GLI) were compared with reference to yield, and preservation of number and pattern of GLI components. The conventional acid-ethanol technique combined with ethanol-ether purification gave high yields and a reproducible pattern of components. Large amounts of tissue were more easily extracted using another technique, based on extraction by boiling, extraction and precipitation with acetone, and — if necessary — salting out. — By means of the latter two techniques mucosal tissue from all of the porcine gastrointestinal tract was extracted and subjected to gel filtration. Glucagon-like peptides were searched for using: — 1. a radioimmunoassay which quantifies gut type glucagon (GTG), as well as pancreatic type glucagon (PTG), 2. a radioimmunoassay highly specific for pancreatic type glucagon (PTG), and 3. a radioreceptor assay based on binding of glucagon to porcine liver cell membranes. — The oesophageal, the fundic, and the antro-pyloric parts of the gastric mucosa contained very small amounts of GLI. The cardiac gland region contained small amounts of a peptide indistinguishable from true glucagon. The duodenal mucosa contained small amounts of true glucagon and may be a smaller, glucagon-like peptide. The mucosa of the small intestine contained large amounts of both high and low molecular weight GTG and, in addition, PTG of high molecular weight and true glucagon. The colon also contained these components with true glucagon in high concentrations. Only small GTG and true glucagon were receptor-active, the former with less than its immunometric potency.  相似文献   

9.
Summary Previous experiments have shown that in an oral glucose tolerance test insulin is mobilized in the first phase independent of the following hyperglycemia. By giving different amounts of glucose (0.5–2.0 g/kg) in conscious trained dogs it was shown that this early phase of insulin secretion was stimulated independently of the administered glucose load by additional mechanisms. These mechanisms, at least partly, were triggered in the nerve endings of the cavity of mouth: their paralysis by mucosal anaesthesia abolished the early IRI-increase in intact animals as well as after feeding glucose to dogs bearing oesophagus fistulas. Spraying sodium cyclamate into the mouth did not produce any IRI-increase. The results indicate that the taste modality sweet is not involved in this reflex response. Conditioned reflexes as a consequence of the training programme or of the daily feeding regime were excluded by control experiments.The authors are grateful to Mrs. Karla Brüllke, Mrs. Helga Schröder, Miss Gisela Schmidt and Miss Helga Schüler for careful technical assistance.  相似文献   

10.
Acute thermal injury to the esophagus has not been reported previously in the radiographic literature. We present a case of a young adult who developed an intramura blister that ultimately communicated with the esophageal lumen. A double-contrast esophagogram outlined the resulting mucosal flap. A brief review of other injuries to the esophagus is included.  相似文献   

11.
Swallowing is a complex mechanism that is based on the coordinated interplay of tongue, pharynx, and esophagus. Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, non-cardiac chest pain, or regurgitation. The major esophageal motility disorders include achalasia, diffuse esophageal spasm, hypercontractile esophagus (nutcracker esophagus), and hypocontractile esophagus (scleroderma esophagus). Other esophageal diseases such as hypopharyngeal (Zenker's) diverticula or gastroesophageal reflux disease also may be sequelae of primary esophageal motility disorder. Finally, a substantial group of patients referred for evaluation of possible esophageal motor disorders have milder degrees of dysmotility—referred to as nonspecific esophageal motor disorder—that are of unclear clinical significance. Medical treatment of esophageal motility disorders involves the uses of agents that either reduce (anticholinergic agents, nitrates, calcium antagonists) or enhance (prokinetic agents) esophageal contractility. Despite the beneficial effect of the various drugs on esophageal motility parameters, the clinical benefit of medical treatment is often disappointing. From clinical and epidemiological studies there is some evidence for a psychological component in the pathogenesis or perception of esophageal symptoms. Further understanding of esophageal pathophysiology, as well as development of new receptor selective drugs, might increase our chances of successful treatment of esophageal motility disorders.  相似文献   

12.
Cervical auscultation is being used more frequently in the clinical assessment of dysphagic patients. The present study was designed to assess symmetry and the reproducibility of swallowing sounds detected simultaneously from bilateral cervical sites. Symmetry of the swallowing sounds acquired using our method was verified because no significant differences were found for any parameters in both time and frequency domain analyses between swallowing sounds detected bilaterally. This result supports the use of a unilateral site for the detection of swallowing sounds. The reproducibility of swallowing sounds was assessed by a coefficient of variation. Results of this analysis suggest that one should evaluate the acoustic characteristics of swallowing sounds from repeated swallows rather than from one swallow.  相似文献   

13.
The androgen-producing cells in the postnatal mammalian ovary are located in the interstitial compartment of the ovary. The most important types of androgen-producing interstitial cells are the cells in the theca interna and the cells of the secondary interstitial glands. There has been some confusion in recent years regarding the terminology used to describe the ovarian androgen-producing cells, namely that theca-interstitial cells are somehow different from theca cells. In fact, these are the same cells. The name theca-interstitial was used by Erickson et al. [1] to describe the theca cells as one of the four androgen-producing cell types in the interstitial compartment of the ovary along with primary interstitial cells which are present only during embryonic development, secondary interstitial gland cells, and steroidogenic cells located in the hilar region of the ovary. For the sake of clarity and according to current convention, the term theca cell will be used throughout this review to refer to cells in the theca interna of the ovarian follicle.  相似文献   

14.
Zusammenfassung Es wurde in einem Inzuchtstamm von rebhuhnfarbigen Italienern durch drei Generationen der Hi-Faktor mit sechs selbst hergestellten Phytoagglutininen untersucht. Das Vorhandensein des Hi-Antigens konnte bestätigt werden. Seine natürliche Nachweisbarkeit beschränkte sich auf weibliche Tiere. Das vorliegende Gen HI, das dominant vererbt wird, konnte bei beiden Geschlechtern und allen Altersstufen bei Vorhandensein des weiblichen Geschlechtshormons (Östrogen) nachgewiesen werden.
Summary The Hi-factor was studied with six self-produced phytoagglutinins in an inbred strain of partridge coloured Italiens through three generations. The presence of Hi-antigen could be confirmed. It can only be demonstrated in female animals. The HI gen, which is inherited in a dominant manner, could be demonstrated in both sexes and at all ages in the presence of female sex hormone (estrogen).


Die Arbeiten wurden mit Mitteln der Deutschen Forschungsgemeinschaft durchgeführt.  相似文献   

15.
Hypertrophic osteoarthropathy: Endothelium and platelet function   总被引:3,自引:0,他引:3  
Summary Hypertrophic osteoarthropathy (HOA) is characterized by finger clubbing, periostosis and arthritis. The pathogenesis of hypertrophic osteoarthropathy is still uncertain. Earlier studies have been focused on the potential role of platelet and endothelium in the pathogenesis of HOA.The aim of this study was to evaluate the circulating levels of endothelin-1 (ET-1), -thromboglobulin (-TG) and platelet-derived growth factor (PDGF) in 21 HOA patients.The circulating levels of ET-1, -TG were significantly higher in HOA patients vs healthy controls, but not vs controls with lung diseases. On the contrary, PDGF was significantly higher in HOA patients vs healthy controls and vs subjects with lung diseases.These findings suggest that endothelium/platelet unit may play a role in the pathogenesis of HOA, and PDGF could induce the changes observed in HOA.  相似文献   

16.
We try to solve the hemodynamic inverse problem of the internal organs in terms of the peripheral pressure pulse spectrum analysis. Side-branch organs are approximated as resonators with own natural frequencies. They are depicted not as ordinary reflection sites but as antennas that receive energy from the main artery and undergo forced oscillations with selective frequencies. Every organ also reacts back to the main artery as a secondary small heart source that generated harmonic forces with maximum amplitude near its own natural frequency. The whole arterial system is in a steady distributed oscillatory state that is the superposition result of encountering the forces generated by the heart and many internal organs. A frequency matching theory of the organ and the main artery is proposed. The Fourier components of the pressure pulse in the arterial system are related to the matching conditions of different organs. In vivo studies in kidney and spleen of rats are provided.  相似文献   

17.
The protective effects of the proton pumpinhibitor lansoprazole on gastric mucosal damage inducedby ethanol-HCl or hemorrhagic shock were investigated inthe present study. The morphometric analysis of gastric histological sections revealed thatlansoprazole dosedependently reduced mucosal injuryevoked by ethanol-HCl (ED50 = 24.3mol/kg) or hemorrhagic shock (ED50 = 38.9mol/kg), these effects being associated with markedincrements of Alcian blue recovery from gastric boundmucus (ED50 = 31.4 mol/kg and 27.6mol/kg, respectively). In addition, lansoprazoleinhibited gastric acid secretion from pylorusligated rats(ED50 = 9.8 mol/kg). Further experiments,performed on rats with ethanol-HCl-induced gastricinjury, indicated that the protective effects of lansoprazole were not modified by L-365,260,suramin, NG-nitro-L-arginine, or systemicablation of capsaicin-sensitive sensory nerves, whereasthey were partly blocked by indomethacin and fullyprevented by N-ethyl-maleimide. In addition, lansoprazoledid not modify somatostatin concentrations in gastricmucosa. The present results provide evidence thatlansoprazole prevents the necrotic damage of gastric mucosa induced by ethanol-HCl or hemorrhagicshock. According to the rank order of ED50values, these effects appear to depend mainly on theenhancement of the gastric mucus barrier rather than on the reduction of acid secretion. It is alsoproposed that an increased production of prostaglandins,as well as an increased availability of sulfhydrylcompounds at level of gastric mucosa may account for the gastroprotective effects oflansoprazole.  相似文献   

18.
Histamine H-2 receptors are thought to mediate gastric acid secretory responses, where-as H-1 receptors supposedly regulate mucosal vascular responses to histamine. In an in vivo chambered canine stomach flap preparation, the H-1 receptor antagonist, tripelennamine, injected intraarterially (22.1 mol/kg) into the stomach flap reduced histamine-stimulated (1.25 /kg/min intravenously) acid secretion by approximately two thirds with a secondary reduction in gastric mucosal blood flow. This antisecretory action does not appear to be due to nonspecific mucosal damage. The H-2 receptor antagonist, metiamide, injected intraarterially (2.5 mol/kg) also inhibited gastric acid secretion by about two thirds as did intravenously injected metiamide (4.5 mol/kg), whereas intravenously administered tripelennamine (40.8 mol/kg) was ineffective as an acid secretory inhibitor. Intraarterial tripelennamine reduced the secretory actions of the H-2 agonist, 4-methyl-histamine (2.2 g/kg/min intravenously), while intravenous metiamide depressed the gastric mucosal dilator responses to the H-1 agonist, 2-methylhistamine (5 g/kg/min intravenously). Both histamine-receptor antagonists also reversed the systemic circulatory depressor effects of histamine and its analogs. These results suggest the need for reevaluation of inferences based upon the assumed specificity of H-2 and H-1 agonists and antagonists.  相似文献   

19.
Detection of aspiration by bedside examination has frequently been found to be clinically inadequate when compared with videofluoroscopy (VF) as the gold standard. In Doncaster, UK, a new multidisciplinary approach to bedside assessment was devised using physiotherapists (PT) performing bronchial auscultation (BA) in combination with the speech and language therapists (SLT) clinical examination of dysphagia. In this study 105 patients referred for VF examination of dysphagia were first tested by the BA team. Comparison was made between the results of the VF team and the results of the BA team in classifying the patients as aspirating or at risk of aspirating. A high degree of agreement was found for risk of aspiration (sensitivity 87%), although specificity was low (37%). BA was highly specific (88%) when confirming the absence of aspiration, but sensitivity to the presence of aspiration was 45%. From the 105 patients tested, the BA team would have failed to modify the diet in only one subject who was aspirating and would have unnecessarily modified the diet of 17 subjects. In conclusion, in the sample population of individuals with complex dysphagia, the BA team approach reliably detected patients identified by VF as at risk of aspiration. In the group of patients identified by VF as aspirating, the BA team proved unreliable in detecting the presence of aspiration, although it did reliably identify patients who were not aspirating. BA is a potentially useful clinical tool which requires further research.Work performed at Doncaster Royal Infirmary and Royal Hallamshire Hospital, Sheffield, UK.  相似文献   

20.
In this study we analyzed the role of substance P (SP) from afferent nerves in ileum contractibility and in the release of inflammatory mediators (neurotensin, Il-1, and TNF-) in ileal mucosa and muscularis layers after a 10-Gy -irradiation of the abdomen. Six hours after irradiation, SP concentrations were lower than in control rats, and 3 days after irradiation SP-induced contractile activity was higher. Irradiation significantly increased the levels of neurotensin, Il-1, and TNF- in both layers. Pretreatment with capsaicin depleted afferent nerve endings of SP and reduced SP levels by about 50%. Capsaicin treatment reduced SP concentrations further, beyond the levels due to irradiation, thereby suggesting that all sources of SP are affected by irradiation. Capsaicin treatment prevented the irradiation from affecting SP-induced contractile response or increasing neurotensin levels. This finding suggests that SP released by afferent nerve endings controls these functions. Proinflammatory cytokine release was not reduced by capsaicin treatment.  相似文献   

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