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PubMed2003

Interleukin-2 and its receptor complex (alpha, beta and gamma chains) in in situ and infiltrative human breast cancer: an immunohistochemical comparative study.

INTRODUCTION: The presence and distribution of interleukin-2 (IL-2) and its receptor complex (Ralpha, Rbeta, Rgamma) were studied in 52 women who were clinically and histopathologically diagnosed with breast tumours (17 in situ and 35 infiltrating), and in 13 women with benign fibrocystic lesions in the breast. METHODS: Immunohistochemistry with antibodies against IL-2, IL-2Ralpha, IL-2Rbeta and IL-2Rgamma was used. A comparative semiquantitative immunohistochemical study between the three breast groups (fibrocystic lesions, in situ tumours and infiltrating tumours) was performed. RESULTS: IL-2 and its three receptor chains were immunodetected in the cytoplasm of epithelial cells. The three receptor chains were also detected on the cell surface. In fibrocystic lesions, immunoreactions to IL-2 (38.5% of cases), IL-2Ralpha (53.8%) and IL-2Rbeta (30.8%) were very weak, whereas immunoreaction to IL-2Rgamma (46.1%) was somewhat more intense. In in situ tumours, the percentages of cases that immunostained positively for IL-2 and its three receptor chains were similar to those observed in fibrocystic lesions, but immunostainings of the four antibodies were more intense. In infiltrative tumours, the percentages of positively stained cases and also immunostaining intensities were approximately twice that found for in situ tumours. Within infiltrating tumours, the percentage of cases showing immunoreaction to IL-2 and their three receptor chains was higher in the patients with lymph node infiltration at the time of surgery. CONCLUSION: The development of breast tumour is associated with an increased expression of IL-2 and its three receptor chains, and this expression also seems to be associated with the malignancy of the tumour.

Aged↗

PubMed2006

Macrophages in experimental rat lung isografts and allografts: infiltration and proliferation in situ.

Alveolar macrophages (AMs) and peribronchial/perivascular macrophages are probably involved in lung allograft damage. We investigate leukocyte infiltration into graft tissue and address the question whether proliferation in situ contributes to macrophage homeostasis and accumulation. Lung transplantation was performed in the Lewis (LEW)-to-LEW and in the Dark Agouti-to-LEW rat strain combination. Graft infiltration by ED1+ and ED2+ (CD163) macrophages was analyzed by immunohistochemistry (IHC) and compared with infiltration by lymphocytes. Cells in the S-phase of the cell cycle were pulse-labeled with BrdU and detected immunohistochemically. Finally, the donor or recipient origin of AMs was determined by IHC and in situ hybridization. ED1+ AMs in allogeneic transplants increased by more than 25-fold from Days 1 to 5. In addition, large, peribronchial/perivascular infiltrates developed containing numerous ED1+ cells. Although AMs in normal rat lungs are CD163-, AMs up-regulated CD163 between Days 4 and 5, reaching maximum values on Day 6. Lymphocytes were less numerous than macrophages. About 16% of the AMs and 10% of the peribronchial/perivascular macrophages were in the S-phase of the cell cycle on Day 2 post-transplantation. No differences in the frequency of BrdU+ macrophages were obvious between isografts and allografts. AMs of donor origin increased in number considerably during allograft rejection. In conclusion, the cellular infiltrate in lung allografts is dominated by macrophages, which exhibit an unusual phenotype and a strong capacity for mitotic self-renewal.

Animals↗

PubMed1993

Cytolytic T cells with Th1-like cytokine profile predominate in retroorbital lymphocytic infiltrates of Graves' ophthalmopathy.

Lymphocytic infiltration of muscular and connective tissues of the retroorbital (RO) space is a histological hallmark of Graves' ophthalmopathy (GO). We have characterized some phenotypical and functional features of T cells derived from RO infiltrates of four GO patients who were submitted to orbital decompression. Fragments of RO tissue were cultured for 7 days in IL-2-conditioned medium in order to generate T cell lines of in vivo activated T cells. Phenotypical analysis of freshly isolated peripheral blood (PB) lymphocytes both from patients and four healthy controls showed a predominance of CD4+ T cells (CD4/CD8 ratios 1.9:2.5), whereas RO-derived T cell lines displayed almost equal proportions of CD4+ and CD8+ cells (CD4/CD8 ratios 0.9:1.2). RO T cell lines and PB T cells from patients and controls were then cloned using a high-efficiency cloning procedure. The phenotypical and functional features of 153 T cell clones (TCC) derived from RO infiltrates were examined and compared with those of 166 and 236 TCC derived from the PB of patients and controls, respectively. CD4/CD8 ratios ranged from 0.8-1.4 in the series of RO-derived TCC and from 1.9-2.2 in the corresponding series of PB-derived TCC. Assessment of lectin-dependent cytolytic activity showed similar proportions of cytotoxic clones in TCC derived from the PB of patients (37%) and controls (38%); most of the cytolytic TCC was CD8+. In contrast, the proportion of cytolytic RO TCC was markedly higher (106/153 = 69%), including 100% of CD8+ and the majority (59/79 = 75%) of CD4+ clones. When compared to TCC derived from the PB of both patients and controls, RO TCC showed remarkably high proportions of both CD8+ and CD4+ clones with a Th1-like cytokine profile, as documented by their ability to secrete IL-2, IFN-gamma, and tumor necrosis factor-alpha (TNF-alpha), but not IL-4 or IL-5. This study provides evidence that cytolytic T cells with Th1 profile of cytokine production predominate in RO infiltrates of GO, a pattern quite similar to those previously described in thyroid infiltrates of Hashimoto's thyroiditis or Graves' disease. The peculiar cytokine secretion profile of RO T cells may be of importance in the pathogenesis of both the tissue alterations and fibrogenic process observed in GO.

Adult↗

PubMed1992

A comparison between preincisional and postincisional lidocaine infiltration and postoperative pain.

We conducted a randomized, double-blind trial to compare the efficacy of preincisional and postincisional wound infiltration with 1% lidocaine (40 mL) on the postoperative pain of 37 patients scheduled for elective inguinal herniotomy. The demand for additional postoperative analgesics occurred earlier in those who received lidocaine infiltration after incision (165 min) than in those who received preincisional lidocaine (225 min, P less than 0.05). The preincisional lidocaine infiltration group also had fewer patients requiring supplemental analgesics (58%) than the postincisional group (94%) (P less than 0.05). We conclude that preincisional infiltration of the surgical wound with lidocaine is a more effective method of providing postoperative analgesia than is postincisional infiltration.

Adolescent↗

PubMed1986

Immunohistochemical analysis of infiltrating lymphocytes in central nervous system tumors.

To investigate cell-mediated immune responses to central nervous system tumors, we immunohistochemically analyzed 32 operative specimens, including 19 primary tumors, 5 recurrent tumors, and 8 metastases, for the presence of infiltrating T lymphocytes. In 1 patient, an additional sample of normal brain was studied. Using monoclonal antibodies against T lymphocyte surface markers with a peroxidase technique on frozen sections, we determined that a mild lymphocytic response was present in 3 of 7 primary glial tumors, 1 of 4 recurrent glial tumors, and in 3 of 9 primary meningiomas. The predominant subset was Leu 2, or suppressor/cytotoxic. In contrast, 5 of 7 intracranial metastatic tumors and 1 extracranial metastasis showed marked infiltration with an overall Leu 3, or helper/inducer, predominance. The remainder of the specimens, including 1 recurrent meningioma, 3 neurinomas, and the normal brain sample, were free of infiltrates. Permanent sections revealed an overall pattern of lymphocytic infiltration similar to that of frozen sections. Although additional studies such as electron microscopy are required to establish definitively the lymphocytic nature of the infiltrates, these results support the concept of the ability of the body to mount a cell-mediated response against central nervous system tumors and imply a differential response to primary and secondary tumors.

Adolescent↗

PubMed1982

Effect of tubulin-binding agents on the infiltration of tumour cells into primary hepatocyte cultures.

The influence of tubulin-binding agents on the infiltration of murine MB6A lymphosarcoma and TA3 mammary carcinoma cells into primary rat hepatocyte cultures was studied. Colchicine, nocodazole and vinblastine reduced the number of infiltrating lymphosarcoma cells, probably by interfering with the adhesion of these cells to the exposed hepatocyte surface. However, the subsequent infiltration of cells that did adhere was not affected or even slightly stimulated. The reduced adhesion appears to be due to an effect on both the MB6A cells and the hepatocytes. In contrasts, adhesion of TA3 cells was not reduced and infiltration was markedly enhanced by these agents, due to an effect on the TA3 cells but probably not on the hepatocytes. These observations support previously described morphological evidence for differences between the infiltration mechanisms of the two tumour cell types. It is concluded that the system within the hepatocytes involved in adhesiveness of the exposed surface to MB6A cells is distinct from that mediating other types of adhesion. The tendency of TA3 cells to invaginate hepatocytes may be due to disturbances in tubulin-dependent processes.

Animals↗

PubMed1995

Involvement of leukotriene B4 in zymosan-induced rat pleurisy: inhibition of leukocyte infiltration by the 5-lipoxygenase inhibitor T-0757.

The role of leukotriene B4 (LTB4) in leukocyte infiltration in zymosan-induced rat pleurisy was investigated by studying the effects of 5-lipoxygenase inhibitors, T-0757 and AA-861, and a cyclooxygenase inhibitor, indomethacin, on leukocyte infiltration and LTB4 levels in the inflammatory exudate of rat pleurisy induced by intrapleural injection of zymosan (20 mg/rat). T-0757 and AA-861 inhibited the infiltration of leukocytes, mainly neutrophils, 3 h after injection of zymosan at a dose of 100 mg/kg, p.o., but indomethacin did not do so at a dose of 5 mg/kg, p.o. LTB4 was detected in the exudate 1 h after zymosan injection, and its level peaked at 3 h (45.4 +/- 8.6 ng/rat) and decreased thereafter. These LTB4 levels were depressed by T-0757 and AA-861 in a dose-dependent manner. T-0757 completely prevented LTB4 production at a dose of 100 mg/kg. These observations suggest that the inhibition of leukocyte infiltration is mediated by the inhibition of LTB4 production, and that LTB4 is one of the main chemical mediators of leukocyte infiltration in zymosan-induced rat pleurisy.

Amides↗

PubMed2001

Effect of hypercholesterolemia on macrophage infiltration after balloon injury to rabbit iliac artery.

Both hypercholesterolemia and vascular injury have been reported to induce macrophage infiltration, but their combined effect and the mechanism by which hypercholesterolemia enhances the infiltration remain to be clarified in vivo. To evaluate the effect of hypercholesterolemia on macrophage infiltration after vascular injury, the iliac arteries of hypercholesterolemic (HC) and normocholesterolemic (NC) rabbits were examined 2h, 1 day, 3 days, 7 days, and 14 days after balloon injury using immunohistochemical staining for macrophages, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1. Nuclear factor kappa-B (NF-kappaB) activation was also evaluated in fresh frozen iliac arteries using the electrophoretic mobility shift assay method. The fundamental difference between HC and NC was the amount of macrophage infiltration seen in HC from 7 days after balloon injury. Two out of 4 HC iliac arteries on the 7th day, and 3 out of 4 HC iliac arteries on the 14th day were positively stained with ICAM-1 in regenerated endothelium and neointima, whereas there were no positively stained NC iliac arteries. Neither HC nor NC tissues showed positive staining with VCAM-1. NF-kappaB was activated in HC 7 and 14 days after balloon injury, but not in NC. In conclusion, in vivo hypercholesterolemia induces macrophage infiltration after balloon injury and it is mediated by increased NF-kappaB activation promoting ICAM-1 expression.

Animals↗

PubMed2005

Growth kinetics and integrin expression of fibroblasts infiltrating devitalised patellar tendons are different from those of intrinsic fibroblasts.

We compared the biological characteristics of extrinsic fibroblasts infiltrating the patellar tendon with those of normal, intrinsic fibroblasts in the normal tendon in vitro. Infiltrative fibroblasts were isolated from the patellar tendons of rabbits six weeks after an in situ freeze-thaw treatment which killed the intrinsic fibroblasts. These intrinsic cells were also isolated from the patellar tendons of rabbits which had not been so treated. Proliferation and invasive migration into the patellar tendon was significantly slower for infiltrative fibroblasts than for normal tendon fibroblasts. Flow-cytometric analysis indicated that expression of alpha5beta1 integrin at the cell surface was significantly lower in infiltrative fibroblasts than in normal tendon fibroblasts. The findings suggest that cellular proliferation and invasive migration of fibroblasts into the patellar tendon after necrosis are inferior to those of the normal fibroblasts. The inferior intrinsic properties of infiltrative fibroblasts may contribute to a slow remodelling process in the grafted tendon after ligament reconstruction.

Animals↗

PubMed2004

Taking the 'ouch' out - effect of buffering commercial xylocaine on infiltration and procedure pain - a prospective, randomised, double-blind, controlled trial.

AIMS: To compare the effect of buffered commercial 1% xylocaine (with 1:200,000 adrenaline) and the unbuffered commercial 1% xylocaine (with 1:200,000 adrenaline) preparation on pain during infiltration and procedure. PATIENTS AND METHODS: A randomised, double blind controlled trial involving 85 patients who underwent bilateral vasectomy under local infiltration anaesthesia. RESULTS: Each patient served as his own control by receiving the buffered commercial preparation on one side and unbuffered commercial preparation on the other. Linear analogue pain scores during infiltration and procedure were recorded and analysed. The study demonstrated that pain perceived by the patient both during infiltration and the procedure was significantly lower when buffered commercial xylocaine was used as compared to the pain perceived with the use of unbuffered commercial xylocaine. CONCLUSIONS: Use of buffered xylocaine is a simple, inexpensive and significantly effective way of reducing pain during infiltration and in surgical procedures performed under local anaesthesia.

Adult↗

PubMed2005

Delineation of patterns of bone marrow mast cell infiltration in systemic mastocytosis: value of CD25, correlation with subvariants of the disease, and separation from mast cell hyperplasia.

In most cases, the diagnosis of systemic mastocytosis (SM) is based on histomorphologic evaluation of the bone marrow. We analyzed mast cell (MC) infiltration patterns in 57 cases of SM and 31 cases of mast cell hyperplasia (MCH). Tryptase immunohistochemical analysis was used for MC detection and CD25 to distinguish neoplastic from normal MCs. The following infiltration patterns were found: I, diffuse interstitial; II, focal, dense; III, focal, dense with an additional diffuse component, located preferentially around focal infiltrates; IV, focal, dense with an additional diffuse component evenly distributed throughout; and V, diffuse, dense. In 29 cases of MCH, MCs formed the type I pattern. The majority of SM cases exhibited patterns II to V; type IV was the most frequent (n = 36). Type V was seen in 3 cases of MC leukemia and 1 case of smoldering SM. In 1 case of SM, type I infiltration was found; the SM diagnosis was based on 3 minor SM criteria. Our data show that the infiltration pattern in SM correlates with the disease subtype and should be recognized as an important aspect in the histomorphologic evaluation of the bone marrow.

Adult↗

PubMed1996

Pulmonary infiltrates following administration of paclitaxel.

The clinical spectrum of hypersensitivity reactions reported with paclitaxel has not included the occurrence of pulmonary infiltrates. This report describes three patients who developed transient pulmonary infiltrates after receiving paclitaxel. These infiltrates were noted 2 days to 2 weeks after administration of paclitaxel. The infiltrates resolved spontaneously in all the patients but one of them did receive steroid therapy. This syndrome of transient pulmonary infiltrates did not reoccur in the two patients who were rechallenged with paclitaxel. Physicians should be made aware of this unique occurrence during the course of treatment with paclitaxel.

Aged↗

PubMed1998

Pulmonary infiltrates in the surgical ICU: prospective assessment of predictors of etiology and mortality.

A prospective cohort study of 129 consecutive patients developing pulmonary infiltrates in the surgical ICU was conducted to determine the predictors and outcome of pulmonary infiltrates. Most common etiologies of pulmonary infiltrates were pneumonia (30%), pulmonary edema (29%), acute lung injury (15%), and atelectasis (13%). Enteral nutrition was associated with a significantly lower incidence of acute lung injury as compared with pneumonia (22% vs 58%, p = 0.012). Patients with liver disease were significantly more likely to have pulmonary infiltrates due to acute lung injury as compared with other etiologies (p = 0.02). Clinical pulmonary infection score (Pugin score) > 6 virtually excluded acute lung injury, pulmonary edema, or atelectasis as etiologies of pulmonary infiltrates. Nosocomial Haemophilus/pneumococcal pneumonia occurred significantly earlier in the ICU as compared with Gram-negative (p = 0.05) or methicillin-resistant Staphylococcus aureus pneumonia (p = 0.01). Pneumonia in trauma patients was significantly more likely to be due to Haemophilus/pneumococcus as compared with all other ICU patients (54% vs 0%, p = 0.0004). These data have implications for treatment of patients with nosocomial pneumonia in the ICU.

APACHE↗

PubMed2004

Normal pulmonary capillary blood volume in patients with chronic infiltrative lung disease and high pulmonary artery pressure.

STUDY OBJECTIVES: Pulmonary capillary blood volume (Qc), a component of diffusing capacity of the lung for carbon monoxide (Dlco), is increased in postcapillary pulmonary hypertension due to valve disease, but is decreased in primitive and thromboembolic pulmonary hypertension. This study was performed to evaluate which way pulmonary Qc is affected in patients with chronic infiltrative lung disease according to the value of systolic pulmonary artery pressure (SPAP). PATIENTS AND METHODS: Twenty-four patients who were nonsmokers and had chronic infiltrative lung disease secondary to connective tissue disease (12 patients), asbestosis (1 patient), sarcoidosis (5 patients), or of unknown origin (6 patients), and 8 control subjects underwent pulmonary function tests and Doppler echocardiography. MEASUREMENTS AND RESULTS: Total lung capacity, alveolar-arterial oxygen pressure difference, Dlco, and conductance of the alveolar-capillary membrane (Dm) did not differ between patients with low SPAP (LPAP) [ie, < 30 mm Hg] or high SPAP (HPAP). Patients with LPAP, but not HPAP, experienced significant decreases in pulmonary Qc, whatever the cause of the disease. There was a strong positive correlation between SPAP and Qc scaled by Dm to account for infiltrative disease severity (r = 0.68; p < 0.001). CONCLUSIONS: We thus conclude that pulmonary Qc is not decreased as expected in patients with chronic infiltrative lung disease and high pulmonary artery pressure. A high Qc/Dm ratio should encourage the physician to look for HPAP compatible with pulmonary hypertension, whatever the etiology of lung infiltrative disease.

Adult↗

PubMed1989

Sensitivity and specificity of electrocardiographic ST-T changes as markers of neoplastic myocardial infiltration. Echocardiographic correlation.

We evaluated the correlations between electrocardiographic ST-T changes (negative T waves, ST segment elevation) and echocardiographic diagnosis of neoplastic infiltration of the myocardium in 95 patients with neoplastic masses in contact with the heart. We compared echocardiographic results to computed tomography, nuclear magnetic resonance, surgery or autopsy data in 49 patients: the concordance was 86 percent. Significant ST-T changes were present in 77.7 percent of the patients with myocardial infiltration at echocardiography. The "false negatives" (normal ECG, nonspecific changes) were mainly related to infiltration limited to the right side of the heart; in some of these cases, the appearance of right bundle branch block was observed. The "false positives" (ST-T changes without echocardiographic signs of infiltration) were observed in the older patients and in those with pericardial effusion or other heart diseases. The ST segment elevation was a more specific sign of myocardial infiltration as compared to negative T waves (86 vs 47 percent). A progression or the disappearance of electrocardiographic and echocardiographic abnormalities was observed during follow-up in 24 cases. Serial electrocardiograms are useful for screening in clinical settings in neoplastic patients; the appearance of ST-T changes or of conduction disturbances should suggest the need for two-dimensional echocardiography in order to define the diagnosis.

Adolescent↗

PubMed2000

Parathyroid adenomas with pronounced lymphocytic infiltration: no evidence of autoimmune pathogenesis.

Pronounced lymphocytic infiltration in parathyroid adenoma is rare, with only six previously reported cases in the literature. The aims of this study are to review the features and investigate the pathogenesis of this rare entity. Two solitary parathyroid adenomas having this feature were reported, and the clinicopathologic features of all the documented cases were reviewed. The nature of the lymphoid infiltrate and the presence of Epstein-Barr virus (EBV) were analyzed to unveil the pathogenesis of this infiltrate. One adenoma was found in a 70-yr-old woman with primary hyperparathyroidism and valvular heart disease. The other was an autopsy finding in a 48-yr-old man who had presented with hypercalcemic crisis. The lymphoid cell population within the tumors was composed of B cells and different subsets of T cells. EBV was not detected in the infiltrates. The lymphocytic infiltrate in parathyroid adenoma is an unusual histologic entity. Its presence is unlikely to imply an autoimmune disorder. We hypothesize that the lesion may be a result of local tissue response to parathyroid adenoma.

Journal Article↗

PubMed1988

[Cell infiltration in various organ and dilatation of the urinary tubule in NON mice].

The non-obese non-diabetic (NON) mouse, which shows no glycosuria, is a subline of the non-obese diabetic (NOD) mouse. Cellular infiltrations in various organs were observed by light and electron microscopy in both sexes from 30 to 300 days after birth. These infiltrations were found in the kidney, pancreas, mandibular gland, parotid gland, exorbital lacrimal gland, and thyroid gland, but not in the adrenal gland, sublingual gland, testis and ovary. The infiltrating cells were mononuclear cells, mostly small lymphocytes. The population and frequency of these cellular infiltrations were weak generally; especially the infiltration into the pancreatic islet, which was very weak compared with that in NOD mice. Dilation of the proximal tubule occurred only in the females at 60 days or more after birth and it gradually increased with age. Numerous acidophil bodies appeared in the epithelial cells and the lumen of these dilated urinary tubules. These bodies were PAS-positive and stained with MT, and They had electron-dense complex structures.

Aging↗

PubMed1986

Cellular analysis in bronchoalveolar lavage fluids in infiltrative and fibrotic stages of idiopathic pulmonary fibrosis.

We performed cellular analysis of bronchoalveolar lavage fluids (BALF) from 20 patients in different stages of idiopathic pulmonary fibrosis (IPF) and compared the results with those from 16 controls and 10 sarcoidosis patients. Patients with IPF were divided into infiltrative and fibrotic groups as diagnosed by transbronchial lung biopsy and chest x-rays. Total cell numbers counted from BALF in IPF patients were not different from those from controls and were lower than in sarcoidosis patients (p less than 0.01). Lymphocytes in BALF were significantly higher in the infiltrative type IPF than in the fibrotic type (p less than 0.05), but there was no significant difference in fibrotic type IPF and control subjects. Numbers of neutrophils and eosinophils counts were not significantly different between infiltrative type and fibrotic type. The neutrophil count in fibrotic type IPF was higher than in control subjects (p less than 0.01) but not in infiltrative type IPF. 67Ga scintiscanning uptake correlated with the lymphocyte population (r = 0.65, p less than 0.01) but with neutrophils. These findings suggest that lymphocytes play a major role in the pathogenesis of the infiltrative type of IPF and that neutrophils are related to the development of fibrotic changes in IPF.

Adrenal Cortex Hormones↗