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Papillary carcinoma of the thyroid. Tall-cell variant with extensive lymphocyte infiltration.

Thirteen cases of tall-cell variant of papillary thyroid carcinoma (PTC) showing extensive lymphocyte and plasma cell infiltration within the fibrous stalks of the papillary architecture were compared with age-, sex-, and tumor size-matched cases of ordinary tall-cell variant without extensive lymphocyte infiltration and also with cases of PTC of the conventional type. All cases of the tall-cell variant of PTC with extensive lymphocyte infiltration exhibited the histologic features of chronic thyroiditis. Dissemination of tumor cells with the thyroid was significantly less frequent than in control cases, but there was no difference between the incidences of lymph node metastasis. Immunohistochemically, the lymphocytes infiltrating the carcinoma focus were mainly CD20+, CD45+, and CD45RO+ cells, that is, basically the same as those found in foci of chronic thyroiditis. No tumor recurrence was observed during the mean follow-up period of 3 years 8 months. The results of this study suggest that the tall-cell variant of PTC with extensive lymphocyte infiltration has less aggressive characteristics and a more favorable prognosis.

Adult↗

Endometrial stromal nodules and endometrial stromal tumors with limited infiltration: a clinicopathologic study of 50 cases.

Experience with endometrial stromal nodules (ESNs) is limited, and no series has been published since the frequent misdiagnosis of highly cellular leiomyomas as ESNs was highlighted. Additionally, although the entirely well-circumscribed margin of most ESNs readily allows a separation from endometrial stromal sarcomas with their typical permeative invasion, some tumors have greater irregularity of their margin than allowable for an ESN following the guidelines of Tavassoli and Norris, but without the typical, and usually extensive, infiltration of endometrial stromal sarcomas. These have been diagnosed by us descriptively as endometrial stromal tumors with limited infiltration. Three cases of this type and 47 ESNs that occurred in patients from 31 to 86 years (mean 53 years) were analyzed. The tumors were typically fleshy and at least in part yellow and ranged from 1.2 to 22 cm (mean 7.1 cm). Seven tumors had one to six focal margin irregularities; in four tumors these did not extend >3 mm beyond the main border of the tumor and were up to three in number. The other three (endometrial stromal tumors with limited infiltration) had four to six irregularities extending up to 9 mm beyond the main border of the tumor. Most neoplasms were densely cellular, but nine were hypocellular with areas that were fibrous, hyalinized, myxoid, edematous, or combinations thereof. The tumor cells almost always had scant cytoplasm, but in one tumor many cells had abundant eosinophilic cytoplasm. There was minimal cytologic atypia. Forty-four tumors had mitotic rates of up to 5 per 10 high power fields, but six had higher rates. Typical arterioles, some of which had hyalinized walls in nine cases, were numerous in all 50 tumors but were conspicuous on low-power examination in only 22. Larger, sometimes thick-walled vessels were seen in 37 tumors but were much less conspicuous than in highly cellular leiomyomas and were often present near the margin of the tumor. The cleft-like spaces of highly cellular leiomyomas were not a feature of these tumors. Twenty-three tumors showed variable degrees of smooth muscle differentiation and sex cord-like differentiation occurred in 12. Cysts were present in 17 tumors and infarct-type necrosis in 34, the latter sometimes causing initial concern for a malignant neoplasm. Follow-up information, available for 32 patients, including five patients whose tumor had some margin irregularity, ranged up to 214 months (mean 43.5 months). All patients were alive with no recurrence. Follow-up information was unfortunately not available for the two tumors with the greatest degree of infiltration. The major conclusions of our study are as follows: ESNs are characteristically soft and yellow; thorough sampling of their margin is mandatory; smooth muscle metaplasia is common and irregular interdigitation of stromal neoplasia with metaplastic smooth muscle may erroneously suggest myometrial infiltration; although typically densely cellular about 20% of ESNs are hypocellular and often fibrous; cellular neoplasms are often punctuated by hyaline plaques; sex cord-like differentiation, broad zones of necrosis and rarely epithelioid cells may complicate the microscopic appearance; typical arterioles are an important microscopic finding but are not always striking, particularly on low-power evaluation; the tumors may have a component of large blood vessels more typical of highly cellular leiomyomas, but they are not as conspicuous as in the latter and the clefts that are frequent in highly cellular leiomyomas are not a feature of ESNs.

Adult↗

A study of the effects of epinephrine infiltration on delayed bleeding in a rat flap model.

Infiltrating the operative site prior to incision with an epinephrine solution will provide vasoconstriction and a dryer operative field. However, some surgeons fear that as the vasoconstrictive effects of the epinephrine subside, smaller vessels will rebleed and a hematoma may result. In this study, 51 rats were operated with two flaps. The ventral pedicled flap, based on the inferior superficial epigastric arteries, and the McFarlane dorsal skin flap were utilized. The perimeter of all flaps was infiltrated with one of the following test infusions: (1) no infiltrate (control group), (2) 1% lidocaine hydrochloric acid (HCl), (3) 2% lidocaine HCl, (4) 1% lidocaine HCl and epinephrine 1:100,000, and (5) 0.5% lidocaine HCl and epinephrine 1:200,000. Flaps were replaced in their beds. Animals were sacrificed 24 hours postoperatively. Flaps were raised at 26 hours and the coagulum weighed. No statistically significant difference was found between the weights of the coagulum of the infiltrated flaps versus the noninfiltrated flaps. Statistical power calculations on the main study flap yielded values greater than 80%. This suggests that the difference in delayed bleeding between noninfiltrated flaps and flaps infiltrated with various combinations of lidocaine and epinephrine was insignificant.

Anesthesia, Local↗

Adoptive immunotherapy involving recombinant human M-CSF and R24 anti-melanoma antibody induces human T-cell infiltration into human melanoma xenografts.

Directed motion toward and infiltration of tumor masses by effector cells is essential for successful adoptive immunotherapy. A human/SCID mouse chimeric system was used to examine whether an antitumor antibody and recombinant human monocyte colony-stimulating factor (rhM-CSF) could promote human T-cell infiltration of a human tumor in vivo. Fourteen days after subcutaneous injection of the human melanoma cell line M-14 into SCID recipients, several adoptive immunotherapy regimens were initiated using activated human T cells, an anti-melanoma monoclonal antibody (MoAb) (R24), and rhM-CSF. Effects on tumor growth and human T-cell infiltration into the tumor were assessed. Compared with other treatment groups, only mice treated with the combination of activated human T cells, anti-tumor MoAb, and rhM-CSF demonstrated a significant cellular infiltrate in the melanoma. Immunohistology demonstrated human T cells present in the tumor up to 7 days after injection. Groups treated with rhRANTES or rmGM-CSF in place of rhM-CSF exhibited markedly less human T-cell infiltration. Additionally, only mice treated with human T cells, R24, and rhM-CSF demonstrated a significant antitumor response in vivo. This model suggests that activated human T cells can be specifically targeted to in vivo tumor sites by combined treatment with an antitumor antibody and rhM-CSF.

Animals↗

Marginal corneal infiltrates: a possible new manifestation of sinus histiocytosis with massive lymphadenopathy.

PURPOSE: To describe unilateral deep marginal corneal infiltrates and chronic anterior uveitis in a young patient with sinus histiocytosis and massive lymphadenopathy. METHODS: A 20-year-old man with a painless enlargement of his cervical lymph nodes was followed for five years after debulking of these nodes on the right side for right chronic anterior uveitis and deep marginal corneal infiltrates. RESULTS: Histological sections of cervical lymph node confirmed the diagnosis of sinus histiocytosis with the typical emperipolesis. The uveitis partially responded to topical corticosteroid treatment but tended to recur upon its withdrawal. The marginal corneal infiltrates resolved gradually over a period of five years. CONCLUSIONS: Marginal corneal infiltrates and uveitis may presumably be associated with sinus histiocytosis. Patients with sinus histiocytosis should also be screened for rare ocular involvement, such as uveitis and corneal infiltrates.

Adult↗

Uterine leiomyomas with lymphoid infiltration simulating lymphoma. A report of seven cases.

Seven women, 35-50 years of age, had uterine leiomyomas with lymphoid infiltration. The leiomyomas ranged from 2 to 12 cm in greatest dimension and contained a variably dense infiltrate of small lymphocytes with scattered larger lymphoid cells and occasionally, numerous plasma cells; germinal centers were identified in some cases and ranged from large and florid to inconspicuous; rarely, eosinophils were present. Most of the tumors contained focal to extensive areas of sclerosis. In all the cases in which adjacent myometrium was available for examination, the lymphoid infiltrate was confined to the leiomyoma or was present to only a minor extent in the adjacent myometrium. Significant lymphoid infiltration of uterine leiomyomas, which appears to be a reactive process, has not been described previously. The polymorphous nature of the infiltrate and its confinement to the leiomyoma distinguish it from malignant lymphoma.

Adult↗

CT of chronic infiltrative lung disease: prevalence of mediastinal lymphadenopathy.

OBJECTIVE: Our goal was to determine the prevalence of mediastinal lymph node enlargement at CT in patients with diffuse infiltrative lung disease. MATERIALS AND METHODS: The study was retrospective and included 175 consecutive patients with diffuse infiltrative lung diseases. Diagnoses included idiopathic pulmonary fibrosis (IPF) (n = 61), usual interstitial pneumonia associated with collagen vascular disease (CVD) (n = 20), idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) (n = 22), extrinsic allergic alveolitis (EAA) (n = 17), and sarcoidosis (n = 55). Fifty-eight age-matched patients with CT of the chest performed for unrelated conditions served as controls. The presence, number, and sites of enlarged nodes (short axis > or = 10 mm in diameter) were recorded. RESULTS: Enlarged mediastinal nodes were present in 118 of 175 patients (67%) with infiltrative lung disease and 3 of 58 controls (5%) (p <0.001). The prevalence of enlarged nodes was 84% (46 of 55) in sarcoidosis, 67% (41 of 61) in IPF, 70% (14 of 20) in CVD, 53% (9 of 17) in EAA, and 36% (8 of 22) in BOOP. The mean number of enlarged nodes was higher in sarcoidosis (mean 3.2) than in the other infiltrative diseases (mean 1.2) (p <0.001). Enlarged nodes were most commonly present in station 10R, followed by 7, 4R, and 5. CONCLUSION: Patients with infiltrative lung disease frequently have enlarged mediastinal lymph nodes. However, in diseases other than sarcoid, usually only one or two nodes are enlarged and their maximal short axis diameter is <15 mm.

Adult↗

Fatty infiltration of the liver in severely burned pediatric patients: autopsy findings and clinical implications.

BACKGROUND: Trauma induces hypermetabolic responses that are characterized by the mobilization of all available substrates. The marked increase of peripheral lipolysis after a burn can lead to the development of fatty liver, which has been associated with immunodepression and increased mortality. METHODS: All autopsies of pediatric burn patients between January 1988 and January 1998 were reviewed. Patient demographics, hospital course, cause of death, and hepatic and septic macroscopic and microscopic findings were recorded. RESULTS: Thirty-seven pediatric patients (4 +/- 1 years old) were included in the study. The mean burn size was 69% +/- 5% total body surface area burned. Eighty percent of the patients presented with fatty infiltration of the liver. Liver weight/body weight ratio was 77 +/- 5 gm/kg, representing 2.1 times the liver weight of age- and sex-matched controls (p < 0.001). Patients with severe fatty infiltration of the liver had a higher incidence of sepsis (p < 0.001). CONCLUSION: Fatty infiltration of the liver is a common condition in fatal burns. Severe fatty infiltration of the liver is associated with an increased incidence of sepsis, although a causative effect could not be found. It is notable that fatty infiltration of the liver occurred in the complete absence of parenteral nutrition.

Burns↗

Immunophenotypic analysis of the inflammatory infiltrates in herniated intervertebral discs.

STUDY DESIGN: The herniated portion of the lumbar disc was analyzed immunohistochemically for inflammatory infiltrates to determine their immunophenotype. OBJECTIVE: To investigate the pathomechanism behind spontaneous regression of herniated discs. SUMMARY OF BACKGROUND DATA: Spontaneous regression of herniated intervertebral discs has been increasingly reported. The inflammatory response of the host has been suggested as a factor in this phenomenon. However, whether the inflammation is induced from direct chemical irritation of the nucleus pulposus material or whether it is secondary to an autoimmune response to the nucleus pulposus remains controversial. METHODS: The herniated portion of the disc was collected from 38 patients who underwent surgery for lumbar disc herniation. Thin cryostat sections were made, and the extent to which inflammatory cells had infiltrated the disc specimen was defined. Then the immunophenotype of cellular infiltrates in the herniated disc specimens was assessed by immunostaining using a series of antibodies for lymphocyte, monocyte, macrophage, and dendritic cell markers. RESULTS: The inflammatory infiltrates in 14 of the 38 herniated discs were subjected to immunohistochemical analysis. None of them expressed the immunophenotypic markers of the lymphocyte (CD20, CD45RO, CD4, CD8, TCRgammadelta), mature monocyte (CD33), or dendritic cell (CD1a, CD80, CD86, S100). Abundant infiltration of CD68-positive cells that lacked CD33 but had a variable amount of CD11b, CD11c, and CD40 likely represents a process of differentiation from monocytes to macrophages. CONCLUSIONS: These findings are consistent with an immunophenotype of inflammatory responses to tissue injury or chemical irritation rather than antigen-specific immune responses. Therefore, understanding the mechanism of tissue repair is fundamentally important in the management of patients with disc herniations.

Adult↗

Suppressor cell activity of cells infiltrating rat renal allografts prolonged by perioperative administration of extracted histocompatibility antigen and cyclosporine.

Suppressor T cells were identified in situ within renal allografts of hosts rendered unresponsive by perioperative administration of donor histocompatibility antigen, which was extracted from donor spleen cells with 3M KCl, combined with cyclosporine (Ag-CsA). Infiltrating cells harvested from Buffalo (BUF, RT1b) renal allografts ten days after transplantation into Wistar-Furth (WFu, RT1u) rats treated with a single i.v. injection of 5 mg 3M KCl-extracted donor antigen (Ag) combined with a three day course of CsA inhibited the mixed lymphocyte culture (MLC) reaction between normal responder WFu and irradiated BUF cells (79.3% suppression, P less than 0.001), but not third-party Brown-Norway (BN, RT1n) stimulator cells (-5.4% suppression, NS). The suppressor effect was not due to cytolysis: the infiltrating cells did not lyse 51Cr-labeled concanavalin A (Con-A) blastoid BUF cells, as did the infiltrating cells from nonimmunosuppressed recipient allografts undergoing rejection responses toward BUF (49% specific cytolysis, E/T = 25), but not third-party BN, target cells five days after transplantation. The suppressor cells were nonadherent to plastic dishes and sensitive to monoclonal antibodies (Mab) W3/13 HLK (pan-T cells: % suppressor -17.9) or cytotoxic/suppressor cells with Mab OX-8 (-5.0% suppression), but not W3/25 (helper; 48.6% suppression, P less than 0.025). Moreover, adoptive transfer of 10(6) infiltrating cells from Ag-CsA-treated recipient allografts into virgin WFu hosts prolonged primary BUF graft survival from 7.2 to 14.0 days (P less than 0.05), but not third-party BN grafts (treated MST = 11.9 +/- 3.9 days versus untreated MST = 11.0 +/- 2.9 days, NS). On the other hand, infiltrating cells from CsA-only-treated recipient allografts could not transfer this effect (MST = 7.7 +/- 0.5 days, P less than 0.01). Finally, retransplantation of the BUF allograft from the Ag-CsA treated rat to a syngeneic, virgin WFu host ten days after primary transplantation yielded prolonged survival with MST 11.4 +/- 2.3 versus control primary graft survival in untreated animals of 7.2 +/- 0.6 days (P less than 0.001). BUF allografts from treated WFu hosts retransplanted into third-party BN rats did not display prolonged graft survival (MST = 9.2 +/- 1.1 days) compared with primary BUF grafts in untreated BN recipients (MST = 9.2 +/- 2.0 days, NS). The presence of suppressor T cells both in the spleen and in situ in renal allografts following Ag-CsA treatment suggests that local mechanisms may augment systemic elements to control the generation of alloimmunity.

Animals↗

Immunohistochemical study of the cells infiltrating human renal allografts by the ABC and the IGSS method using monoclonal antibodies.

Sixty renal allograft tissues obtained from 29 patients were stained with hematoxylin and eosin. These tissues were histologically classified into 4 patterns according to the distribution pattern of the infiltrating cells: normal, focal, focal-diffuse, and diffuse types. Clinical signs of acute rejection were observed in 88% of the patients with the diffuse type infiltration, and 83% of those with the focal-diffuse type infiltration but in only 13% of those with the focal type infiltration. Twenty-four renal allografts were analyzed by the ABC and the IGSS methods using monoclonal antibodies. The number of T cells (Leu 1) accounted for about 80% of the total number of infiltrating cells; 2-8% of the cells were B cells (Leu 12); about 10% were NK/K cells (Leu 7); and 4-6% were monocytes/macrophages (Leu M3). As to helper/inducer T cell (Leu3a) and killer/suppressor T cell (Leu2a), which are T lymphocyte subsets, there were more Leu3a- than Leu2a-positive cells in focal type tissue, but there were more Leu2a- than Leu3a-positive cells in focal-diffuse and diffuse type tissue. In most cases that developed clinical signs of acute rejection, there were more Leu2a- than Leu3a-positive cells. The Leu3a/Leu2a ratio in most of the AZA-administered cases dropped immediately after the transplantation and maintained a low value, but in the CSA-administered cases it decreased gradually post-transplant.

Adolescent↗

Kinetics of intragraft cytokine expression, cellular infiltration, and cell death in rejection of renal allografts compared with acceptance of liver allografts in a rat model: early activation and apoptosis is associated with liver graft acceptance.

BACKGROUND: Liver transplants in the rat strain combination PVG-to-Dark Agouti are spontaneously tolerated, whereas kidney transplants in the same strain combination are rejected in 7-9 days. METHODS: To identify organ-specific differences that might yield further information about the mechanism of tolerance induction in this strain combination, liver or kidney grafts, spleen, and draining lymph nodes were harvested at days 1, 3, 5, and 7, and examined by immunohistochemistry, terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay, and reverse transcriptase-polymerase chain reaction for interferon-gamma, interleukin (IL)-2, IL-4, and IL-10. RESULTS: Renal allograft rejection was associated with the progressive development of an intense mononuclear cell infiltrate. Markers of lymphocyte activation and cytokine up-regulation appeared from day 3, and many apoptotic parenchymal cells were noted on days 5-7, at the peak of rejection. Conversely, liver allograft tolerance was associated with more rapid infiltration by activated T cells and earlier increases in cytokine expression, but with a more limited degree of cellular infiltration. Concurrent with the early activation, high levels of apoptosis were found in areas of leukocyte infiltrate, paralleling the disappearance of activated T cells from the graft between days 3 and 5. CONCLUSIONS: Apoptosis of infiltrating leukocytes in liver allografts may represent an important process in the induction of spontaneous liver transplant tolerance and may underlie the abortive nature of the effector response observed within tolerated livers. In contrast, activated cells in renal allografts in the same strain combination survive and proliferate, express high levels of cytokines, and are efficient in bringing about graft destruction.

Animals↗

Human T cells infiltrate and injure pig coronary artery grafts with activated but not quiescent endothelium in immunodeficient mouse hosts.

BACKGROUND: We have previously demonstrated that human artery grafts transplanted to immunodeficient mice are infiltrated and injured by unsensitized allogeneic human T cells. We extended our investigations to human anti-porcine xenoresponses in this model. METHODS: Pig coronary artery segments were interposed into the infrarenal aorta of severe combined immunodeficiency/beige mice. After 7 days, certain recipients were reconstituted with human leukocytes and/or treated with proinflammatory cytokines. The grafts were harvested after 1-70 days and examined by histology, immunohistochemistry, and morphometry. RESULTS: Pig artery grafts from untreated mice had no evidence of injury, leukocytic infiltrate, or endothelial cell activation up to 70 days postoperatively, despite deposition of murine complement. Host reconstitution with human peripheral blood mononuclear cells resulted in a discrete population of circulating T cells that did not infiltrate or injure the grafts up to 28 days after adoptive transfer. Administration of porcine interferon-gamma for up to 28 days sustained the expression of graft vascular cell adhesion molecule-1 and major histocompatibility complex antigens, but did not initiate recruitment of human leukocytes. In contrast, treatment with human tumor necrosis factor for 7 days induced the de novo expression of porcine E-selectin by graft endothelial cells and elicited human T cell infiltration and human peripheral blood mononuclear cell-dependent vascular injury. CONCLUSIONS: The human peripheral blood mononuclear cell-severe combined immunodeficiency/beige mouse model identifies a significant difference between human T cell allogeneic and xenogeneic responses in vivo. Xenografts with quiescent endothelium are not infiltrated or injured by T cells under the same conditions in which allografts are rejected. Activation of pig coronary artery endothelial cells by human tumor necrosis factor, but not porcine interferon-gamma, elicits cellular xenoresponses.

Animals↗

Effect of a subanesthetic dose of intravenous ketamine and/or local anesthetic infiltration on hemodynamic responses to skull-pin placement: a prospective, placebo-controlled, randomized, double-blind study.

Insertion of cranial pins for stabilization of the head can result in a marked hypertensive response, which may adversely affect cerebral hemodynamics. The efficacy of a subanesthetic dose of intravenous ketamine (0.5 mg/kg) and/or lidocaine infiltration (1%) at pin fixation sites before pinning was studied in a prospective, double-blind, placebo-controlled, randomized trial of 40 patients. The subjects were divided into four groups of 10. Patients belonging to the placebo and lidocaine groups received intravenous normal saline (NS), followed by local infiltration with NS at pin insertion sites in the placebo group and 1% lidocaine in the lidocaine group. Patients belonging to the ketamine and ketamine-lidocaine groups received intravenous ketamine followed by local infiltration with NS in the ketamine group, and lidocaine infiltration in the ketamine-lidocaine group. Heart rate (HR) and invasive mean blood pressure (MBP) were recorded before intravenous medication and then at various time intervals until 15 minutes after pin fixation. Intergroup comparison of MBP and HR by 2-way analysis of variance revealed a significant difference between the groups and various time points (P < .05). Post hoc analysis revealed maximum increase in MBP each hour in the placebo group. Mean blood pressure response in the ketamine group was similar to the placebo group. Significant attenuation of MBP and HR was observed in the lidocaine and ketamine-lidocaine groups (P < .05). A minimal increase in HR was observed in the lidocaine-ketamine group. The current study demonstrates maximum attenuation of hemodynamic responses when a subanesthetic dose of intravenous ketamine (0.5 mg/kg) is administered with 1% lidocaine infiltration.

Adolescent↗

The value of clonality in the diagnosis and follow-up of patients with cutaneous T-cell infiltrates.

The diagnosis of early stages of cutaneous T-cell lymphoma (CTCL) is often difficult, especially for lesions that are at the borderline between reactive and neoplastic skin T-cell infiltrates. T-cell monoclonality in these lesions is considered by some to be an important prognostic factor of neoplastic evolution, whereas others claim that clonality can also be found in benign skin infiltrates and is therefore of limited diagnostic value. To address this controversy, the authors analyzed retrospectively eight patients with lymphocytic skin lesions who progressed to CTCL, and three patients with recurrent T-cell lymphocytic infiltrates who had not developed CTCL. From a total of 65 biopsies of eight progressing patients, 32 were diagnosed as histologically malignant and 33 were diagnosed as benign or borderline. The authors found clonality by either polymerase chain reaction or Southern blot analysis in 88% of malignant and in 79% of nonmalignant lesions. None of the 37 biopsies of non-progressing patients was clonal. These results indicate strongly that the presence of monoclonality in T-cell skin infiltrates is related closely to the risk of developing CTCL. The value of clonality as a marker of malignancy is supported by the absence of T-cell clonal populations in all infiltrates from patients who had not progressed to lymphoma.

Blotting, Southern↗

In-situ immunophenotyping study of hepatic-infiltrating cytotoxic cells in chronic active hepatitis C.

OBJECTIVE: Beside the hypothesis of a direct viral cytopathy, several lines of evidence argue in favour of hepatic damage triggered by immune-mediated mechanisms in hepatitis C virus (HCV) infection. The intrahepatic localization of HCV antigen-specific cytotoxic T-lymphocytes (CTLs) to disease sites has been described; however, very few data are available about the degree and the role of hepatic-infiltrating natural killer (NK) cells in chronically HCV-infected subjects. DESIGN: In a series of percutaneous needle liver biopsies obtained from 35 consecutive untreated patients with chronic active hepatitis C, we performed an in-situ immunophenotyping study to evaluate the degree of cytotoxic NK cell infiltration as compared to CTLs, the hepatocyte expression of human major histocompatibility complex antigens class I and class II (HLA-I and HLA-II), and cell adhesion molecules (CAM) in the context of liver inflammatory infiltrates. The data were correlated with the histological activity index (HAI) of disease. RESULTS: In-situ immunophenotyping analysis of CAM provided evidence for the intrahepatic expression of leucocyte adhesion molecules (CD11a and CD2) and their corresponding ligands on hepatocytes (CD54 and CD58) in all cases. A significant parallel expression of CD11a and CD54 as well as CD2 and CD58 structures, restricted to hepatic lobules within the disease sites, was also observed, even if their induction exhibited different degrees of correlation with biological and/or histological activities. A membranous pattern of HLA-I and HLA-II antigen expression on hepatocyte clusters was found in all tissue samples, although HLA-I expression was significantly higher than HLA-II. Moreover, lymphocyte subset analysis displayed a CD8+ T-cell lobular infiltration within inflammatory and/or spotty necrosis areas in all cases, while CD4+ T-cells were confined to the portal and periportal levels. A few scattered CD56+ and CD16+ NK cells, mainly distributed at periportal areas within inflammatory and/or necrotic foci, were detected in 7/35 (20%) and in 5/35 (14.2%) cases, respectively. On the other hand, CD8+ T-cell lobular expression exhibited a linear correlation with HAI (r: 0.698, P < 0.01). Finally, cytotoxic cell infiltration degree did not correlate with HCV serotypes. CONCLUSION: Our findings suggest a limited role for NK cells in the immune mechanism of liver injury in chronic active hepatitis C, while providing further support for the involvement of CD8+ T-cells at disease sites.

Adult↗

Eosinophil infiltration and activation at the gastric ulcer margin in rats.

BACKGROUND: Recruitment and activation of eosinophils have been studied intensely in asthma and other allergic diseases. Less is known about the infiltration and behaviour of eosinophils during gastric ulcer healing. AIM: To examine the tissue infiltration and activation of eosinophils in the ulcer margin at different time points after ulcer induction (days 1-15). METHODS: Eosinophil peroxidase (EPO) staining and transmission electron microscopy (TEM) were used to observe eosinophil infiltration and activation in rats with acetic-acid-induced ulcer in the oxyntic mucosa. The distribution of macrophages was evaluated by immunocytochemistry using the macrophage-specific antibodies ED1 and ED2. RESULTS: There was a prominent increase in eosinophils around the ulcer margin at day 1 after ulcer induction, which peaked at day 5. TEM revealed characteristic signs of eosinophil activation, including cytolysis and piecemeal degranulation. Eosinophil cytolysis was the major form of activation, seen most frequently at day 5. A few scattered apoptotic eosinophils could also be observed. In normal controls and sham-operated rats, activated eosinophils were detected rarely. The distribution pattern of infiltrated eosinophils closely resembled that of macrophages at the ulcer margin. However, in the central part of the granulation tissue (at day 5) only macrophages could be found. CONCLUSIONS: There is marked infiltration and signs of activation of eosinophils together with macrophages at the margin of newly formed ulcers.

Animals↗

Interactions between angiotensin II and NF-kappaB-dependent pathways in modulating macrophage infiltration in experimental diabetic nephropathy.

NF-kappaB-dependent pathways play an important role in macrophage infiltration and kidney injury. NF-kappaB is regulated by angiotensin II (AII). However, the role of this pathway in diabetic nephropathy has not been clearly delineated. First, the activation of NF-kappaB, monocyte chemoattractant protein-1 (MCP-1), and macrophage infiltration in the diabetic kidney were explored, in a temporal manner. The active subunit of NF-kappaB, p65, was elevated in the diabetic animals in association with increased MCP-1 gene expression and macrophage infiltration. Second, the effects of treatment for 4 wk with the AII type 1 receptor antagonist valsartan, the AII type 2 receptor antagonist PD123319, or pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB and on these parameters were assessed. These treatments were associated with a reduction in p65 activation, MCP-1 gene expression, and macrophage infiltration. These findings demonstrate a role for activation of NF-kappaB, in particular the p65 subunit, in the pathogenesis of early renal macrophage infiltration in experimental diabetes. In the context of the known proinflammatory effects of AII, it is postulated that the renoprotection conferred by angiotensin II receptor antagonism is at least partly related to the inhibition of NF-kappaB-dependent pathways.

Angiotensin II↗