首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 359 毫秒
1.
Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were examined for effects on human squamous carcinoma cells. IFN-gamma inhibited proliferation at concentrations between 100 and 1,500 units/ml and the inhibitory effects were potentiated by TNF-alpha. Inhibition of cell growth was not accompanied by cytotoxicity. Combined treatment with the two cytokines also inhibited cell-substrate adhesion and altered the morphology of the cells. The treated cells were large and flattened. These morphological features are similar to those that have been previously described for normal keratinocytes induced to differentiate by a variety of means. The changes in biological properties were accompanied by alterations in production of extracellular matrix components - e.g., fibronectin and thrombospondin. Synthesis of both components was decreased following treatment. The cytokine-induced alterations in squamous carcinoma cell properties were fully reversible. These findings indicate that malignant squamous epithelial cells may be similar to their normal counterparts in their responses to IFN-gamma and TNF-alpha. In the malignant cells, however, these cytokines do not appear to induce permanent phenotypic changes.  相似文献   

2.
The aim was to examine anti‐tumor necrosis factor α (anti‐TNFα) therapy influence changes on Th17 and Th22 cells in patients with spondyloarthritis (SpA), and its correlation with changes in clinical and magnetic resonance imaging (MRI) activity and chronicity scores. The Th17 and Th22 cells were assessed at baseline, after 12 and 52 weeks of anti‐TNFα therapy by flow cytometry (ClinicalTrials.gov NCT4682724). The percentages of both Th17 and Th22 cells were increased by 70% at baseline compared with healthy controls (both p < 0.01). During treatment, these two subsets increased further to be 170% (Th17) and 123% (Th22) above levels in healthy controls (both p < 0.01). The same subsets decrease their expression of IL‐23R significantly during the observation period (p < 0.05). High levels of Th17 and Th22 cells at baseline were associated with the degree of chronic changes in the sacroiliac joints on MRI and a good clinical response to anti‐TNFα treatment after one year. Plasma levels were not associated with clinical changes. Th17 cells, and Th22 subsets, increased during one year of anti‐TNF‐α therapy in SpA, regardless of their clinical improvement. This supports that both the Th17 and Th22 subsets could be involved in the progression in SpA.  相似文献   

3.
An innate immune response to bacterial components is speculated to be involved in the pathogenesis of primary biliary cirrhosis (PBC). Recently, CD4-positive T helper type 17 (Th17) cells, characterized by the secretion of interleukin (IL)-17, have been implicated in the pathogenesis of autoimmune diseases. Human Th17 cells are generated from Th0 cells by IL-6 and IL-1β and maintained by IL-23. In this study, the role of IL-17 in PBC and its association with biliary innate immunity were examined. Using cultured human biliary epithelial cells (BECs), the expression of Th17-related cytokines and chemokines and changes therein on treatment with pathogen-associated molecular patterns (PAMPs) and IL-17 were examined. Immunohistochemistry for IL-17 and Th17-related cytokines was performed using tissue samples of human liver. Consequently, the expression of IL-6, IL-1β, IL-23p19 and IL-23/IL-12p40 mRNAs, and their up-regulation by PAMPs, were found in BECs. Moreover, BECs possessed IL-17-receptors and stimulation with IL-17 induced production of IL-6, IL-1β, IL-23p19 and chemokines. Several IL-17-positive cells had infiltrated damaged bile ducts and the expression of IL-6 and IL-1β was enhanced in the bile ducts of PBC patients. In conclusion, IL-17-positive cells are associated with the chronic inflammation of bile ducts in PBC which is associated causally with the biliary innate immune responses to PAMPs.  相似文献   

4.
The anti-immunoglobulin reactivity of two monoclonal, dual specific, autoantibodies, BV 17-45 and BV 04-01 was examined. The current study further defined the anti-immunoglobulin autoreactivity of these MoAbs to be Fc-specific. Both BV 17-45 and BV 04-01 bound their own Fc domains in addition to Fc regions of other MoAbs of similar isotype with varying levels of activity. The different anti-Fc reactivity patterns of BV 17-45 and BV 04-01 suggested that these MoAbs recognized distinct epitopes. Neither BV 17-45 nor BV 04-01 bound Fab fragments or single-chain antibody derivatives, which confirmed that the anti-immunoglobulin reactivity of these autoantibodies was Fc-specific. In addition, abrogation of anti-Fc reactivity was observed when affinity-labelled MoAbs were used as coating antigens in solid-phase ELISAs. These results implied that active-site ligand binding induced conformational changes which altered the Fc epitope(s) recognized by BV 17-45 and BV 04-01.  相似文献   

5.
To study the structural features of fetal rat duodenal mucosa associated with histogenesis of villi, duodena from 15- to 19-day fetuses were examined by light and electron microscopy. The duodenal epithelium of 15-to 18-day fetuses was stratified. Distinctive junctional complexes associated with membrane-bounded vesicles and cilia-like structures were seen in the deeper epithelial layers at 15 and 16 days. Small lumina, designated “secondary lumina,” lined with a variable number of microvilli developed between epithelial cells at these junctional complexes during the sixteenth through eighteenth days. Degenerative changes and exfoliation of superficial epithelial cells were obvious in 17- and 18-day fetuses. In 18-day fetuses, aggregates of mesenchyme had invaginated the basal aspect of the stratified epithelium. Concomitantly, the number of epithelial layers overlying these mesenchymal projections was decreased. In 19-day fetuses, well formed, short duodenal villi lined by a simple columnar epithelium which included goblet and endocrine cells were evident. Injection of ferritin into the main duodenal lumen of 17-day fetuses failed to reveal continuity between the main lumen and the secondary lumina. However, continuity between many secondary lumina and the main lumen was demonstrated in 18-day fetuses. Thus, major morphological features associated with villus formation in fetal rat duodenum include: (1) formation of many secondary lumina in primitive stratified epithelium, (2) eventual fusion of these lumina with the main duodenal lumen, by their continued growth coupled with exfoliation of degenerating superficial layers and (3) upward growth of mesenchyme towards the lumen as cell exfoliation and expansion of secondary lumina take place.  相似文献   

6.
Trichomonas vaginalis infection may be influenced by the vaginal concentrations of estrogens. We have investigated the effects of 17β-estradiol and dehydroepiandrosterone sulfate (DHEAS) on the ecto-5′-nucleotidase activity in fresh clinical (VP60) and in long-term-grown (30236 ATCC) isolates of T. vaginalis. In vitro exposure to DHEAS and 17β-estradiol did not induce any changes in adenosine monophosphate (AMP) hydrolysis in these isolates. The treatment of parasites in the presence of DHEAS (0.01–1.0 μM) for 2 h inhibited AMP hydrolysis in VP60 isolate, whereas there were no significant changes in nucleotide hydrolysis in the presence of 17β-estradiol. DHEAS and 17β-estradiol (0.01–1.0 μM) for 2 h inhibited AMP hydrolysis in 30236 isolate. The 12 treatment with 0.1 μM DHEAS inhibited AMP hydrolysis, whereas 17β-estradiol did not alter the nucleotide hydrolysis in VP60 isolate. Our findings have shown that the complex effect of steroid hormones and their receptors on T. vaginalis may promote changes in ecto-5′-nucleotidase activity during exposure to these hormones.  相似文献   

7.
The histopathologic features of the adrenal glands in three cases of congenital 17 alpha-hydroxylase deficiency are described in relation to clinical and endocrine findings. Diffuse or nodular adrenocortical hyperplasia, particularly in the zonae fasciculata and reticularis, was observed in all cases examined. The hyperplastic adrenal cortices were composed of cells with morphologic features of hypercorticism and hyperstimulation. Myelolipomatous lesions were detected in two cases. These morphologic findings were consistent with excessive adrenocorticotropic hormone secretion in this disorder. In all the cases examined, the plasma aldosterone concentration was within normal limits, and plasma renin activity was suppressed prior to dexamethasone treatment. Morphologically, however, hyperplasia of the cells with abundant mitochondria and smooth endoplasmic reticulum seemed to involve the zona glomerulosa. Nonencapsulated nests of hypertrophied cortical cells in periadrenal tissue were remarkable in one case. From these morphologic findings, we postulated hyperfunction of the zona glomerulosa as well as involvement of corticosteroids from the zona glomerulosa in the pathophysiology of this disorder.  相似文献   

8.
Atrial fibrillation (AF) is commonly encountered in clinical practice and typically it is treated with pharmacological agents. Some patients whose arrhythmias are resistant to pharmacological therapy undergo the maze procedure, which is a surgical treatment. The atrial appendages are removed as part of the surgical procedure. These appendages often demonstrate mycocyte hypertrophy, vacuolar degeneration and other changes that may be seen in cardiomyopathies. We examined 19 of these appendages and compared them with 17 autopsy controls, 12 of whom had documented coronary atherosclerotic disease and 5 of whom did not. We semiquantitatively measured the amount of vacuolar degeneration, interstitial fibrosis, myocyte hypertrophy and intramyocardial adipose tissue. Univariate and multivariate analysis was performed and revealed that vacuolar degeneration were significantly more common in appendages of patients with arrhythmias than the autopsy controls (P<.0004). The other three histological features studied were not significantly different in the three groups. Ultrastructural studies on atrial tissue excised during the maze procedure, retrieved from the paraffin blocks, revealed degenerative changes similar to cardiomyopathic myocardial tissue. Vacuolar degeneration is commonly seen in atrial appendages removed in patients with chronic AF. Myocyte hypertrophy is a nonspecific finding and may occur in patients with arrhthymias and coronary artery disease.  相似文献   

9.
Nearly 30% of the breast cancer patients in the Taiwanese community have their diseases diagnosed before the age of 40. Their 5-year survival rate is poorer than that of their late-onset breast cancer counterparts. Genomic abnormalities between these two breast cancer age groups were compared using comparative genomic hybridization (CGH) analyses. The sample set was made up of 44 early-onset (<35 years old) and 54 late-onset cases (>63 years old). Frequent CGH changes were noted, such as gains on 8q, 1q, and 17q and losses on 16q, 17p, and 8p. These were very similar for the two age groups, as well as for Taiwanese women and other ethnic populations. In contrast, several less common lesions, such as gains on 16p and 8p and losses on 11q and 9p, were significantly different between the early- and late-onset breast tumors. In addition, more profound chromosomal changes were consistently associated with the more advanced-stage tumors, and less expression of the estrogen and the progesterone receptors, and of HER-2/neu. About 19% of the breast cancers examined carried a TP53 mutation in exons 4-9. Of these, 88% (15/17) were missense point mutations and these were distributed randomly along the tested gene fragments without apparent clustering, as has been shown in certain other ethnic or regional studies. On average, patients carrying these TP53 mutations had 9.5 CGH lesions per case, compared to only 2.8 changes in samples that had no TP53 mutation. Our results indicate that certain genomic lesions, especially 11q loss, may play a role in early-onset breast tumor formation, and that combined use of genomic patterns and molecular targets may provide a useful tool for diagnostic, therapeutic, and prognostic purposes.  相似文献   

10.
In the kainate model of epilepsy, electrophysiological and anatomical modifications occur in inhibitory circuits of the CA1 region of the rat hippocampus. Using postembedding GABA immunocytochemistry and electron microscopy, we characterized perisomatic GABA and non-GABA synaptic contacts in CA pyramidal cells, and GABAergic interneurons of stratum oriens/alveus and stratum lacunosum-moleculare, and examined if changes occurred at these synapses at two weeks post-kainate treatment. We found that, in control rats, the number and total length of perisomatic GABA synapses were significantly smaller (approximately 40-50%) in lacunosum-moleculare interneurons than in oriens/alveus interneurons and pyramidal cells. Additionally, the number and total length of perisomatic non-GABA synapses were different among all cell types, with these parameters increasing significantly in the following order: pyramidal cells相似文献   

11.
Fibrous dysplasia and osteofibrous dysplasia are both benign fibro-osseous lesions of the bone and are generally seen during childhood or adolescence. Histologically, the features of these bone lesions sometimes look quite similar, but their precise nature remains controversial. We retrospectively studied clinicopathologic findings in 62 cases of fibrous dysplasia and 20 cases of osteofibrous dysplasia with regard to their anatomic location and histological appearance. From among these cases, the immunohistochemical expressions of c-fos and c-jun proto-oncogene products and bone matrix proteins of type I collagen, osteonectin, osteopontin, and osteocalcin were evaluated in 20 typical fibrous dysplasias and 17 osteofibrous dysplasias using paraffin sections, and these expressions were then assessed semiqnantitatively. Microscopically, fibrous dysplasia showed various secondary changes, such as hyalinization, hemorrhage, xanthomatous reaction, and cystic change in 22 of the 62 cases (35%). This was a higher incidence than in osteofibrous dysplasia, in which only 2 of the 20 cases (10%) showed such changes. In the elderly fibrous dysplasia cases, the cellularity of fibroblast-like cells was rather low, and those cases were hyalinized. Almost all of the cases of fibrous dysplasia and osteofibrous dysplasia showed positive expressions of c-fos and c-jun products. The expressions of type I collagen and osteopontin showed no difference between fibrous dysplasia and osteofibrous dysplasia. Immunoreactivity for osteonectin in bone matrix was detected in only 1 case of fibrous dysplasia (1 of 20), whereas it was recognized in 14 of the 17 cases of osteofibrous dysplasia. Furthermore, the immunoreactivity for osteocalcin in bone matrix and fibroblast-like cells was higher in fibrous dysplasia than it was in osteofibrous dysplasia, semiquantitatively. Our immunohistochemical results regarding osteonectin and osteocalcin suggest that the bone matrix of fibrous dysplasia is somewhat more mature than that of osteofibrous dysplasia, and that the fibroblast-like cells in fibrous dysplasia share some phenotypic features with osteoprogenitor ceils of normal osteogenic tissues. Fibrous dysplasia and osteofibrous dysplasia share Some similar histological features, including c-fos and c-jun expressions, although different clinicohistologic features and immunohistochemical expressions of osteonectin and osteocalcin were observed. These features suggest that the mechanisms behind the development of fibrous dysplasia and osteofibrous dysplasia are similar, but this is not necessarily indicative of a closer relationship between the 2 diseases.  相似文献   

12.
《Human pathology》1998,29(4):359-363
Gonadotropin-releasing hormone (GnRH) agonists are commonly used in the treatment of uterine leiomyomas, but little is known about their histological and cellular effects on these neoplasms. We examined a cellular proliferation index as determined by the nuclear antigen Ki-67 and proliferating cell nuclear antigen (PCNA) expression, estrogen receptor (ER), and progesterone receptor (PR) expression in 27 leiomyomas from patients treated with the GnRH agonist leuprolide acetate (LA) and compared them with 33 untreated controls. All leiomyomas were removed by myomectomies from premenopausal woman after 2 to 6 months of LA treatment or in the follicular phase of the menstrual cycle in the untreated controls. Histological features examined included cellularity, nuclear atypia, vascular changes (dilated, thickened, or thrombosed vessels), edema, calcification, hemorrhage, necrosis, hyalinization, and mitotic activity. Although no difference was found between GnRH-treated and non-treated groups with respect to most histological features examined, immunohistochemical studies showed a significant decrease in the cellular proliferation index, ER, and PR expression in the LA-treated cases compared with nontreated controls. The cellular proliferation index, ER, and PR expression decreased by 85%, 49%, and 36%, respectively, in the LA-treated group as compared with controls (P < .001). A subset of cases from the LA-treated and nontreated groups were also analyzed with respect to bcl-2 (an inhibitor of apoptosis) expression, and no significant difference between the LA-treated and nontreated groups was observed with both groups showing a strong (>75% of cells) cytoplasmic staining pattern. Results of this study show that LA treatment of leiomyomas results in a decrease in number of cycling cells.  相似文献   

13.
A series of 105 patients with acute promyelocytic leukemia (APL) has been cytogenetically investigated at the Department of Hematology of the Saint-Louis Hospital (Paris) between 1977 and 1990. Sixty-two patients were examined at diagnosis, 32 in relapse, and 11 both at diagnosis and in relapse. The typical t(15;17)(q22;q12) or variants of this translocation were observed in all but four patients. The t(15;17) was the only change in 47 cases at diagnosis and in 21 examined in relapse. The most frequent secondary change was trisomy 8 (17% at diagnosis). More or less complex chromosomal abnormalities in addition to t(15;17) were present in six patients at diagnosis, and in 17 patients in relapse. Rearrangements of 2q35-q37 and del(11p) were observed only in relapse and may thus be nonrandom secondary changes. Cytogenetic studies performed on 19 patients treated with all-trans retinoic acid did not indicate that this treatment induces chromosomal abnormalities.  相似文献   

14.
The structural effects of diabetes and subsequent insulin treatment upon the contractile and supporting elements of the rat myocardium were examined at progressive stages of both untreated and treated disease. Diabetes was induced by intravenous injection of alloxan, and tissue was examined after 6, 12, and 26 weeks. Insulin treatment began after 12 weeks of diabetes and tissue from these animals was examined after the same intervals. Within the cardiocytes, diabetes produced a focal yet progressive loss of myofibrils, transverse tubules, and sarcoplasmic reticulum, and separation of the fasciae adherens was evident at the intercalated disk. Mitochondrial damage was not evident. These cytoplasmic alterations were accompanied by intercellular and perivascular deposition of connective tissue, thickening of the endothelial cytoplasm with pinocytotic hyperactivity, and characteristic basal laminar changes. When insulin treatment began after 12 weeks of diabetes, most, but not all, of these changes were reversed, and this reversal was essentially complete within 6-12 weeks. Even with longer periods of insulin treatment, cardiocytes still exhibited scattered areas of myofibril loss and extracellular matrix was retained. In contrast, diabetic changes in the intercalated disk and capillaries, including their basal laminae, were completely and rapidly reversed. It is hypothesized that the structural manifestations of diabetic cardiomyopathy consist of two major components; the first is a short-term, physiologic adaptation to metabolic alterations, while the other represents degenerative changes for which the myocardium has only a limited capacity for repair.  相似文献   

15.
The value of the Papanicolaou-stained vaginopancervical (Fast) smear in the detection of chlamydial infection has been disputed. We examined 116 satisfactory Fast smears from 203 women enrolled in the Johns Hopkins Fertility Control Clinic and compared tissue-culture results with cytopathologic detection using various published morphologic criteria. All Chlamydia culture-positive cases were reviewed, and certain cytologic features considered helpful in the detection of chlamydial infection in cervical smears obtained from this selected high-risk population were identified. The changes that had the highest correlation with tissue culture included fine vacuolation of metaplastic endocervical cells, giving their cytoplasm a rarefied "moth-eaten" appearance. Using these criteria, cytopathologic changes of chlamydial infection were observed in 24 of 28 cases of tissue-culture-positive cases and in 8 of 88 tissue-culture-negative cases. The sensitivity and specificity of the Fast-smear cytodiagnosis of Chlamydia infection utilizing these morphologic changes and compared with tissue culture were 86% and 91%, respectively. Other cytologic features, including inflammatory background and intracytoplasmic structures consistent with initial and intermediate chlamydial bodies within the metaplastic cells, were found to be useful although less specific and less sensitive. The implications of these diagnostic features, the conditions to be considered in their differential diagnosis, and the pitfalls of chlamydial cytodiagnosis and the chlamydia culture studies have been critically reviewed. Study design and the high unsatisfactory cervical smear rate are discussed.  相似文献   

16.
This study examined whether estrogen treatment can improve immunity in male mice after combined ethanol and burn injuries. 17beta-Estradiol [estrogen, given subcutaneously (s.c.)] or oil (control) was administered at 30 min and 24 h postinjury. At 48 h postinjury, ethanol/burn-injured mice demonstrated significant suppression of cellular immunity. Estrogen treatment restored the delayed-type hypersensitivity (P<0.01) and splenocyte-proliferative (P<0.05) responses, reduced macrophage interleukin-6 (IL-6) (P<0.05), and increased survival after bacterial challenge (P<0.01). In vitro neutralization of IL-6, combined with macrophage supernatant experiments, confirmed that the beneficial effects of estrogen treatment were mediated through modulation of macrophage IL-6 production. Moreover, estrogen treatment resulted in a decrease in splenic nuclear factor-kappaB (NF-kappaB) activation in injured mice. There were no changes in cellular NF-kappaB or IkappaBalpha protein expression or IkappaBalpha phosphorylation at serine 32. Taken together, these studies suggest that estrogen treatment of injured male mice improves cellular immunity through direct modulation of NF-kappaB activation.  相似文献   

17.
Fine structural changes in cryptogenic fibrosing alveolitis and asbestosis   总被引:6,自引:0,他引:6  
Lung biopsies from 17 patients with cryptogenic fibrosing alveolitis of a cellular rather than fibrotic pattern were examined by transmission electron microscopy in the hope that such cases would show features of pathogenetic significance. Further selection was made by choosing minimally affected areas. There was no ultrastructural evidence of immune complex deposition but alveolar epithelial and capillary damage was frequently found (17 and 14 of the 17 cases respectively). Alveolar epithelial injury consisted of patchy necrosis and regenerative hyperplasia. Alveolar capillary injury consisted of cytoplasmic swelling and basement membrane thickening and reduplication. Many of these features have not been emphasized in previous reports and their prominence in early stages of the disease suggest that they may have pathogenetic significance, possible mechanisms of which are discussed. Similar findings identified during the course of this study in 8 asbestos workers suggest that similar pathogenetic mechanisms may operate in asbestosis.  相似文献   

18.
19.
Childhood asthma and wheezy bronchitis are the most frequent chronic diseases of childhood. Unfortunately their clinical symptoms are similar--which makes it difficult to distinguish between the two, and therefore decide on proper treatment of patients. The aim of the study was to establish the parameters leading to right diagnosis. The study was performed in 50 children aged 3-7 years with recurrent wheezy bronchitis. All patients underwent allergological examinations (skin tests with inhaled allergens, personal and family history and serum total and specific IgE levels). 42 of them were tested for ventilatory parameters with bronchodilatation test. Three features of atopy were found in 21 (42%) patients, two features in 7 (14%) patients. In 31 (62%) children at least one feature of atopy was shown. 7 (17%) of the examined children had significant bronchodilatation after salbutamol inhalation. Finally in 24 (48%) of children suffering from wheezy bronchitis, bronchial asthma was diagnosed. The diagnosis was confirmed by antiasthma tic treatment with cromones or inhaled corticosteroids. In great majority (88%) of patients bronchial asthma was atopic. In 23% wheezy bronchitis children not diagnosed with bronchial asthma features of atopy were observed. They are of bronchial asthma risk group.  相似文献   

20.
The mechanisms underlying the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remain largely unknown. CRSwNP has garnered considerable public health concern owing to its high incidence and unsatisfactory treatment outcomes. Herbal remedies are promising candidates for the treatment of CRSwNP. We examined the utility of andrographolide, a diterpenoid lactone extracted from the Chinese herb Andrographis paniculata, an anti-inflammatory agent for CRSwNP treatment by evaluating interleukin (IL)-6 and IL-17 production and monitoring T helper 17 (Th17) differentiation of peripheral blood mononuclear cells (PBMCs) isolated from 20 Chinese CRSwNP patients and 11 control subjects. All CRSwNP patients exhibited clinical features of CRSwNP. Andrographolide significantly inhibited IL-6 and IL-17 production, suppressed p-Stat3 expression, and inhibited Th17 differentiation of PBMCs in vitro. These findings suggested that andrographolide has useful anti-inflammatory properties and could be used for the treatment of CRSwNP.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号