SEARCH · PubMed Health

Results for “Infiltrative”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

PubMed2001

Effects of social isolation on ehrlich tumor growth and tumor leukocyte infiltration in mice: evidence of participation of the submaxillary salivary gland.

OBJECTIVE: Considering previous studies on stress and Ehrlich tumor growth from our laboratory and also known cell growth and behavior-related properties of submaxillary salivary gland products, we studied the effects of stress by social isolation, in combination or not with sialectomy (submaxillary gland ablation), on growth and leukocyte infiltration into Ehrlich adenocarcinomas. METHODS: 5 x 10(7) tumor cells/ml were inoculated into the footpads of mice and tumor growth was evaluated by measuring paw thickness on alternate days. Ten days after inoculation, tumors were harvested and processed for immunocytochemical analysis of tumor-infiltrating leukocytes (TIL) and nerve-like growth factor (NGF)/epidermal growth factor (EGF)-positive tumor cells. T and B lymphocyte, NK cell and macrophage percentages were calculated. RESULTS: Sialectomy slightly reduced tumor growth and caused a significant increase in NK cell infiltration of tumors (p < 0.05). Social isolation caused a highly significant enhancement of both tumor growth (p < or = 0.05) and percentage of macrophages infiltrating tumors (p < 0.05). Sialectomized isolated animals showed few significant changes in tumor growth rate (p < or = 0.05), but presented increased percentages of NK cells, macrophages and B lymphocytes (p < 0.05). A reduction in the percentage of NGF+ tumor cells was also observed (p < 0.05). All of these effects were seen only in 8-month-old mice, but not in younger animals. CONCLUSION: A possible link between salivary gland factors, tumor growth and TIL patterns was considered, suggesting that growth factors may modulate tumor leukocyte infiltration as well as tumor growth rate.

Animals↗

PubMedDate not supplied

Interleukin-2 immunotherapy of murine cytomegalovirus retinitis during MAIDS correlates with increased intraocular CD8+ T-cell infiltration.

AIDS-related human cytomegalovirus retinitis continues to be an important sight-threatening disease in AIDS patients who do not respond to highly active antiretroviral therapy. We have shown previously that systemic cytokine immunotherapy with interleukin-2 (IL-2) will protect against experimental murine cytomegalovirus (MCMV) in mice with a murine retrovirus-induced immunodeficiency syndrome (MAIDS). Since IL-2 serves as a Th1 immunoregulatory cytokine, we hypothesized that IL-2-induced protection against MCMV retinitis during MAIDS would correlate with a measurable increase in the number of natural killer (NK) cells and/or CD8+ T cells that infiltrate the eye in response to MCMV infection of the retina. We therefore performed a study to quantify and compare the number of NK cells and CD8+ T cells that infiltrate MCMV-infected eyes in untreated and IL-2-treated mice with MAIDS at 3 days and 5 days after subretinal MCMV inoculation. Double-label flow cytometric analysis revealed the detection of measurable numbers of both NK cells and CD8+ T cells in MCMV-infected eyes of untreated MAIDS mice destined to develop retinitis. In contrast, IL-2 immunotherapy during MAIDS correlated with a 10-fold increase by day 5 after inoculation in the number of CD8+ T cells in MCMV-infected eyes destined to be resistant to retinitis. However, IL-2 immunotherapy during MAIDS had no appreciable effect on the number of NK cells that infiltrated MCMV-infected eyes. Taken together, our findings suggest that function of cytotoxic lymphocytes that infiltrate the eye may be more important than absolute numbers of cytotoxic lymphocytes that infiltrate the eye when assessing the protective effects of IL-2 immunotherapy on MCMV retinitis during MAIDS.

AIDS-Related Opportunistic Infections↗

PubMed2006

Hypertension induces oxidative stress but not macrophage infiltration in the kidney in the early stage of experimental diabetes mellitus.

BACKGROUND: The combination of diabetes and hypertension increases the incidence and severity of kidney disease in an additive manner. Inflammatory and oxidative stress mechanisms contribute to renal damage in both diabetes and hypertension. Therefore, we investigated whether renal macrophage infiltration and oxidative stress events are additive from the beginning in diabetic animals with coexisting hypertension. METHODS: Diabetes was induced in spontaneously hypertensive rats (SHRs) and their genetically normotensive control Wistar Kyoto (WKY) rats by streptozotocin injection at 12 weeks of age for 10 days, and the effects of hyperglycemia on renal macrophage infiltration and oxidative stress were evaluated. RESULTS: Blood pressure was higher in SHR than in WKY groups. Markers of oxidative stress-induced DNA and protein modification, 8-hydroxy- 2'-deoxyguanosine (8-OHdG) and nitrotyrosine, respectively, and the antioxidant glutathione levels were found to be similar in WKY-control and WKY-diabetic groups. However, 8-OHdG was significantly elevated (p = 0.014), the nitrotyrosine level tended to be elevated (p = 0.068) and the glutathione level was significantly reduced (p = 0.034) in the SHR-diabetic group compared to the SHR-control group. On the other hand, glomerular and tubulointerstitial macrophage infiltration was significantly higher in both WKY-diabetic and SHR-diabetic groups than the respective control groups. CONCLUSIONS: A short duration of diabetes mellitus induces renal oxidative stress in the presence of hypertension; however, renal macrophage infiltration becomes evident in early diabetes regardless of the presence or absence of hypertension. We conclude that the combination of diabetes and hypertension adversely affects oxidative stress in the kidney, but the combination has no additive effect on renal macrophage infiltration, at least in early diabetes.

Animals↗

PubMed1997

Mechanism of infiltration and activation of glomerular monocytes/macrophages in IgA nephropathy.

Glomerular deposits of fibrin-related antigens (FRA), C3c, membrane attack complex (MAC) were examined by the immunoperoxidase method on 176 renal biopsy specimens from 120 cases with IgA nephropathy including 56 cases with sequential biopsies. On 47 sets of repeated renal biopsy specimens, the glomerular infiltration of the following immune cells was examined by the indirect immunoperoxidase method; immune cells positive for C3bi receptor (C3biR; CR3/CD11b, CR4/CD11c), HLADR antigen and several leukocyte surface markers (CD45R, CD3, CD15 and CD68). Twenty-four-hour urine protein (UP) at the renal biopsy was also evaluated. The glomerular deposition of FRA was inversely correlated with C3c/MAC deposition (p < 0.00001). Most cases (163 of 176) were classified into the following two types; type C with dominant deposition of C3c (97 cases) and type F with dominant deposition of FRA (66 cases), except for 13 cases with equivalent deposits of C3c and FRA (7 cases, type B) and without C3 or FRA deposits (6 cases, type O). In 56 rebiopsied cases, apparent conversion from type F or C into the other was observed only in one case though a few cases in type C lost or reduced C3c deposition to an equivocal type at the follow-up biopsy, which were included in type C', an expanded category of type C. In the whole cases, the glomerular infiltration of immune cells was significantly correlated with FRA deposition (p < 0.0002) but not with C3c. Glomerular CD11c+ cells were significantly correlated with C3c deposition in type C' (p < 0.0001), but not in type F. Glomerular HLADR positive immune cells were significantly correlated with glomerular CD3+ T cells in type F (p < 0.001), but not in type C'. In type C', UP was significantly correlated with glomerular CD11c+ cells (p < 0.0001) but not with CD 15+ or HLADR+ cells. On the other hand, in type F, UP was significantly correlated with CD 15+ and HLADR+ cells (p < 0.001) but not with CD11c+ cells. These results suggested that there are multiple pathways in inducing glomerular infiltration of immune cells in IgA nephropathy. In type C, local activation of complements might primarily induce immune cell infiltration through C3biR and these C3biR+ cells are involved in inducing proteinuria. On the other hand, in type F, in which complement activation is weak, immune cells might infiltrate directly through their Fc receptor or MHC class II antigens, and might be activated by T-cell/macrophage interaction to induce proteinuria.

Adult↗

PubMed1989

Fine-needle aspiration biopsy sampling in renal transplantation: interstitial cellular infiltrates and major histocompatibility complex class-II antigen expression in renal tubular cells.

The dynamics of major histocompatibility complex (MHC) class-II (DR) antigen products in renal tubular cells and cellular infiltrations in the interstitium of the kidney following renal transplantation without immunosuppressive therapy are presented. DR antigen in 27 normal kidneys and in 18 of 19 kidneys transplanted as autograft showed no DR-antigen expression on their tubular cells. These DR-antigen-negative tubular cells could be induced to express the antigen during courses of untreated rejection both in primary (n = 6) and repeat (n = 4) allografts. Parallel to the increasing DR-antigen expression in the allograft, the autologous kidney expressed this antigen with the same time dependency and with the same intensity. Graft infiltrating cells were evaluated by daily fine-needle aspiration biopsy and core biopsy. Induction of DR antigen was associated with a significant infiltration of blastogenic cells and monocytes/macrophages in the allograft. During rejection of the allograft no cellular infiltrate was noted in the autograft, but during an initial time period after allograft removal cellular infiltrates were seen. Following both courses of rejection DR antigen returns to negative by 6-8 days as did blastogenic cells and monocytes/macrophages in the autograft interstitium. Inducible antigen expression in normally DR-antigen-negative allograft parenchymal cells during rejection is shown to depend on inflammatory cells in the graft. The antigen expression is not restricted to the tissue transplanted, but also affects autologous tissue of the host organism.

Animals↗

PubMed1996

Restricted usage of T-cell receptor Valpha-Vbeta genes in infiltrating cells in aortic tissue of patients with Takayasu's arteritis.

BACKGROUND: Infiltration by perforin-secreting killer lymphocytes, such as T cells and natural killer cells, has been shown to be involved in the pathogenesis of vascular cell damage in Takayasu's arteritis. METHODS AND RESULTS: To investigate the immunological mechanisms involved, especially the nature of T-cell infiltration in Takayasu's arteritis as well as atherosclerosis, we analyzed the expression of T-cell receptor (TCR) Valpha and Vbeta genes in infiltrating cells in the aortic tissue of patients with Takayasu's arteritis and the atherosclerotic aortic aneurysm by polymerase chain reaction (PCR). We also analyzed the expression of cytokine genes by PCR. We found that the repertoires of TCR Valpha as well as Vbeta gene transcripts in Takayasu's arteritis were restricted. The infiltrating cells expressing Valpha2, Valpha16, Valpha17, Vbeta7, and Vbeta13.1 were found in 3 of 4 patients. In contrast, TCR Valpha-Vbeta repertoires in atherosclerotic aortic aneurysm were polyclonal. There was no significant difference in the pattern of cytokine gene expression between the two diseases. CONCLUSIONS: The restricted usage of TCR Valpha as well as Vbeta genes by infiltrating T cells in Takayasu's arteritis may indicate that a specific antigen in the aortic tissue was targeted. Our findings provide the evidence that distinct immunological mechanisms are involved in the pathogenesis of Takayasu's arteritis and atherosclerotic aortic aneurysm.

Aged↗

PubMed1999

Nitric oxide synthase gene therapy rapidly reduces adhesion molecule expression and inflammatory cell infiltration in carotid arteries of cholesterol-fed rabbits.

BACKGROUND: Hypercholesterolemia reduces nitric oxide bioavailability, manifested by reduced endothelium-dependent vascular relaxation, and also induces vascular adhesion molecule expression and inflammatory cell infiltration. We have previously shown that gene therapy with NO synthase in hypercholesterolemic rabbits substantially reverses the deficit in vascular relaxation. In the present study, we show that NO synthase gene therapy rapidly and substantially reduces vascular adhesion molecule expression, lipid deposition, and inflammatory cell infiltration. METHODS AND RESULTS: Thirty male New Zealand White rabbits were maintained on a 1% cholesterol diet for 11 to 13 weeks, then underwent carotid artery gene transfer with Ad.nNOS or Ad.betaGal (recombinant adenoviruses expressing neuronal NO synthase or beta-galactosidase, respectively), or received medium alone in a sham procedure. Arteries were harvested at 1 and 3 days after gene transfer, and the following parameters were determined by immunohistochemical and image-analysis techniques: intercellular adhesion molecule-1, vascular cell adhesion molecule-1, lipid deposition by oil red O staining, lymphocyte infiltration (CD43-positive cells), and monocyte infiltration (RAM-11-positive cells). In Ad.nNOS-treated arteries, all markers were significantly decreased relative to Ad. betaGal or sham-treated arteries within 3 days after gene transfer. Ad.nNOS had a particularly striking impact on monocyte infiltration; as early as 24 hours after gene transfer, Ad.nNOS-treated arteries had >3-fold fewer monocytes than Ad.betaGal- or sham-treated arteries. CONCLUSIONS: NO synthase gene therapy rapidly ameliorates several markers of atherosclerosis in the cholesterol-fed rabbit.

Animals↗

PubMed1999

Monocyte infiltration and adhesion molecules in a rat model of high human renin hypertension.

Hypertension and kidney damage in the double transgenic rat (dTGR) harboring both human renin and human angiotensinogen genes are dependent on the human components of the renin angiotensin system. We tested the hypothesis that monocyte infiltration and increased adhesion molecule expression are involved in the pathogenesis of kidney damage in dTGR. We also evaluated the effects of long-term angiotensin-converting enzyme (ACE) inhibition, AT1 blockade, and human renin inhibition on monocyte recruitment and inflammatory response in dTGR. Systolic blood pressure and 24-hour albuminuria were markedly increased in 7-week-old dTGR as compared with age-matched normotensive Sprague Dawley rats. We found a significant monocyte/macrophage infiltration in the renal perivascular space and increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the interstitium, intima, and adventitia of the small renal vessels. alphaLbeta2 integrin and alpha4beta1 integrin, the corresponding ligands for ICAM-1 and VCAM-1, were also found on infiltrating monocytes/macrophages. The expression of plasminogen activator inhibitor-1 and fibronectin in the kidneys of dTGR were increased and distributed similarly to ICAM-1. In 4-week-old dTGR, long-term treatment with ACE inhibition (cilazapril), AT1 receptor blockade (valsartan), and human renin inhibition (RO 65-7219) (each drug 10 mg/kg by gavage once a day for 3 weeks) completely prevented the development of albuminuria. However, only cilazapril and valsartan were able to decrease blood pressure to normotensive levels. Interestingly, the drugs were all equally effective in preventing monocyte/macrophage infiltration and the overexpression of adhesion molecules, plasminogen activator inhibitor-1, and fibronectin in the kidney. Our findings indicate that angiotensin II causes monocyte recruitment and vascular inflammatory response in the kidney by blood pressure-dependent and blood pressure-independent mechanisms. ACE inhibition, AT1 receptor blockade, and human renin inhibition all prevent monocyte/macrophage infiltration and increased adhesion molecule expression in the kidneys of dTGR.

Angiotensinogen↗

PubMed1996

Analysis of heart-infiltrating T-cell clonotypes in experimental autoimmune myocarditis in rats.

Experimental autoimmune myocarditis (EAM) resembles the lethal giant cell myocarditis seen in humans, and the recurrent forms lead to dilated cardiomyopathy (DCM). EAM in rats induced by a subcutaneous injection of cardiac myosin has been shown to be a T cell-mediated autoimmune disease. Alpha beta T cells have proved to be important by the observation that antibodies to alpha beta T-cell receptor (TCR) prevent disease progression. Alpha beta cells recognize antigenic peptides bound to major histocompatibility (MHC) molecules by alpha beta TCR, and complementarity determining region 3 (CDR3) is considered the most important region for antigen recognition. To elucidate the nature of this T cell-mediated myocarditis, we analyzed TCR V beta chains of heart-infiltrating T cells. In the early state of EAM, none of 22 TCR V beta chain transcripts seemed to be dominant by reverse transcription-polymerase chain reaction analysis of total RNA and flow cytometric analysis. On the other hand, single-strand conformation polymorphism analysis of TCR V beta 8.2, V beta 8.5, V beta 10, and V beta 16 cDNA amplified by polymerase chain reaction encompassing the CDR3 revealed oligoclonal expansion in heart-infiltrating T cells isolated from animals at various disease stages. cDNA encoding V beta CDR3 from heart-infiltrating and pericardial effusion T cells in rats with EAM revealed more restricted sequences than did cells from rats with normal spleens. Clones from distinct lesions of the same animal were identical, and clones from heart-infiltrating and pericardial effusion T cells from the same animal showed overlap. Thus, CDR3 of the TCR beta chain may be important in rat EAM, and heart infiltrating T cells are considered to recognize the specific antigen.

Amino Acid Sequence↗

PubMed1995

Modulation of cytokine-induced eosinophil infiltration by phosphodiesterase inhibitors.

The effects of selective phosphodiesterase (PDE) isoenzyme inhibitors on eosinophil airway infiltration induced by intratracheal administration of recombinant human cytokines were investigated in the guinea pig. Recombinant human IL-5 and IL-8 elicited a concentration-dependent increase in the number of eosinophils in the bronchoalveolar lavage (BAL) fluid. In contrast, no effect was observed after intratracheal injection of recombinant human IL-3 or recombinant human RANTES. Pretreatment with the PDE IV inhibitors rolipram or Ro 20-1724 or the nonselective PDE inhibitor theophylline 1 h before intratracheal injection of IL-5 significantly reduced the number of eosinophils in the BAL fluid at 48 h. In contrast, the selective PDE III inhibitors milrinone and SK&F 94-836 and the PDE I/V inhibitor zaprinast did not inhibit the airway eosinophil infiltration induced by IL-5. Betamethasone also significantly inhibited the IL-5-induced eosinophil infiltration in BAL fluid. Administration of rolipram or betamethasone 1 h before IL-8 significantly reduced airway eosinophil infiltration. Because the selective PDE IV inhibitors markedly inhibited eosinophil infiltration in guinea pig airways induced by cytokines, it is suggested that PDE IV inhibitors have antiinflammatory effects in the airways and may be useful in the treatment of asthma.

Animals↗

PubMed1980

The prognosis of lung cancer originating as an infiltrate. Data from the Philadelphia Pulmonary Neoplasm Research Project.

In a periodic screening study of 6,027 older men, 121 developed lung cancer during the 10 yr of observation. The over-all 5-yr survival rate was 8%, but when the 121 men were subdivided according to the initial radiographic appearance of cancer, a group of 23 with ill-defined peripheral lesions that we labeled "infiltrates" had the best prognosis over the first 5 yr of follow-up. This advantage tended to disappear thereafter. The men whose tumors originated as infiltrates also had the highest resection rate and were detected most frequently within 7.5 months of a negative film. The infiltrates tended to be smaller than the well-defined peripheral tumors that we designated round lesions. In 8 of 13 instances with radiographic follow-up, the infiltrates assumed the appearance of round lesions or irregular masses. These observations suggested that the infiltrate is often a biologically earlier lesion than other radiographic forms of lung cancer.

Humans↗

PubMed1994

Interleukin-4-dependent pulmonary eosinophil infiltration in a murine model of asthma.

The establishment of animal models of asthma is critical to elucidate the mechanisms involved in the pathogenesis of the disease. In the present study, we have used a parasite antigen from Schistosoma mansoni eggs, which induces a TH2 response, to elicit a pulmonary inflammatory reaction that resolves after 3 to 4 days. Histologic examination of the lungs of soluble egg antigens (SEA) or saline vehicle-challenged mice demonstrated a large influx of cells in the antigen- but not vehicle-challenged mice, thus demonstrating an antigen-specific reaction. A characteristic influx of eosinophils could be detected as early as 8 h, with significant increases at 24 to 72 h after challenge. An assessment of the bronchial alveolar lavage (BAL) fluid demonstrated dominant neutrophil infiltration at 8 h, with a subsequent decrease to background by 48 h. In addition, peak monocyte infiltration occurred at 24 h, and peak eosinophil extravasation into the airway was shown at 48 h. The examination of leukocyte infiltrates in the interstitium in dispersed lung preparations again demonstrated early neutrophil and monocyte infiltration at 8 h after challenge, with increases in lymphocyte and eosinophil infiltrates at 24 h. Examination of interleukin-4 (IL-4) production in the BAL fluid demonstrated the presence of IL-4 early in the response, with levels peaking between 8 and 24 h after antigen challenge, with no detectable IL-4 in the saline vehicle-challenged mice. Mice treated with anti-IL-4 antibodies demonstrated a tenfold decrease in BAL eosinophil influx at 48 h after challenge and a reduction in total pulmonary leukocyte cellularity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1976

Tissue T and B cell infiltration of primary and metastatic cancer.

Immunofluorescent techniques were utilized to identify the types of infiltrating lymphocytes adjacent to human malignant tumors arising from a wide range of anatomic sites. 24 of 29 primary tumors and 5 of 8 metastatic lesions showed varying degrees of lymphocytic infiltration. T cells predominated in the infiltrates in primary tumors (mean 80%, range 50-100%) and this pattern was evident regardless of anatomic site or the presence or absence of metastatic spread. By contrast, B cells predominated at the margins of three of five tumor metastases. Mononuclear cells bearing the Fc receptor were not a prominent component of the infiltrates associated with either primary tumors or metastases, but tumor cell binding of fluoresceinated IgG aggregates was observed in 12 of 29 primary tumors. A significant reduction in peripheral blood T cell numbers occurred in a third of the patients studied. This decrease was not clearly related either to the extent of local tumor T cell infiltration or to the presence of disseminated disease. These preliminary findings provide a descriptive analysis of the local and systemic distributions of immunocompetent cells in cancer.

Adult↗

PubMed1993

Tissue infiltration in a CD8 lymphocytosis syndrome associated with human immunodeficiency virus-1 infection has the phenotypic appearance of an antigenically driven response.

HIV-1 infection may initiate to an HLA-associated response designated diffuse infiltrative lymphocytosis syndrome, characterized by increased numbers of circulating CD8 T cells that infiltrate salivary glands, lungs, gastrointestinal tract, and kidneys. Since this response could either be an antigenically driven process induced by HIV-1 or a lymphoproliferation of cells with neoplastic or unusual features, we sought to define the phenotype of the cellular populations, the nature of tissue derangement, and the tissue localization of virus in diffuse infiltrative lymphocytosis syndrome. Circulating CD8 T cells were greatly increased while CD4 T cell numbers remained in the range found in asymptomatic seropositive persons. The majority of CD8 and CD4 T cells in both blood and tissues had the memory phenotype of CD29+ (beta 1 integrin) and CD11a+/CD18 (beta 2 integrin) expression, but lacked markers of recent activation. A proportion of the circulating CD8 T cells also expressed CD57 (Leu 7) but not other markers of natural killer cells. HIV-encoded proteins were identified in tissue macrophages located in periacinar areas of the salivary glands. CD54 (intercellular adhesion molecule-1), a ligand for the CD11a integrin, was strongly expressed on postcapillary venule endothelium within lymphoid foci, and HLA-DR molecules were found on limited regions of ductular epithelium adjacent to lymphoid aggregates. These findings suggest that (a) the visceral lymphocytic infiltration in diffuse infiltrative lymphocytosis syndrome is an antigen-driven, and MHC-determined, host immune response to an element associated with HIV-1 infection, and (b) that the specific adhesive molecule interactions mediating the cellular influx, as well as the subsequent tissue damage, reflect altered patterns of gene expression in tissues undergoing an immune response.

AIDS-Related Complex↗

PubMed1995

Tensile properties of resin-infiltrated demineralized human dentin.

The ability of adhesive resins to restore the physical properties of demineralized dentin has not been well-documented. The unfilled resins that are used for adhesion have relatively low moduli of elasticity and limited ability to increase dentin stiffness, although they may increase the ultimate tensile strength of dentin. This study tested the hypothesis that resin infiltration of demineralized dentin can restore its tensile properties to those of mineralized dentin. Small (ca. 0.5 mm thick x 0.5 mm wide) specimens of demineralized human dentin were infiltrated with one of five different dentin bonding resins over many hours, to determine how these resins altered the tensile properties of dentin. Tensile stress and strain were measured in these and control (mineralized and demineralized) specimens until their ultimate failure. The results indicate that some adhesive resins, after infiltrating demineralized dentin, can restore and even exceed the ultimate tensile strength of mineralized dentin. These resins increased the modulus of elasticity of resin-infiltrated dentin to values equal to or greater than those of the resins but far below those of mineralized dentin. Although the conditions in this experiment were far removed from the manufacturer's recommendations or clinical practice, the results support the potential of resin infiltration for reinforcing dentin.

Acid Etching, Dental↗

PubMedDate not supplied

Acute liver failure as the initial manifestation of hepatic infiltration by a solid tumor: report of 5 cases and review of the literature.

BACKGROUND: Acute liver failure is a rare complication of metastatic liver disease with a high mortality. Recognition of malignant infiltration of the liver as the cause of acute liver failure could be a diagnostic challenge. PATIENTS: The medical files of 5 patients with acute liver failure due to metastatic liver disease collected over a 4-year period (1997-2000) in our department were reviewed. RESULTS: No patient had a past history of cancer. The interval from jaundice to encephalopathy ranged from 7 to 12 days (median, 10). Physical examination revealed hepatomegaly and deep jaundice in all patients. AST elevation ranged from 147 to 1870 IU/L (median, 716 IU/L) and ALT elevation from 74 to 556 IU/L (median, 138 IU/L). All patients died within 4-14 days (median, 7) of admission. None had papillary edema or decerebrate posture before death. Four patients had concurrent renal impairment. Liver imaging studies in 2 of the 5 patients were nondiagnostic and the malignant liver infiltration was confirmed postmortem. Liver histology in all cases showed massive tumoral infiltration of the hepatic sinusoids with diffuse replacement of hepatocytes. The primary tumors were colon, gastric, small cell lung, pancreas and cancer of unknown origin. CONCLUSIONS: Malignant infiltration of the liver should be taken into account in the differential diagnosis of rapidly progressive liver failure. Although effective chemotherapy has improved the survival of patients with metastatic liver disease, there has been no change in the course and outcome of acute liver failure due to malignant infiltration of the liver over the last 2 decades. A proper diagnosis by liver biopsy is mandatory to prevent such patients from being considered for liver transplant.

Adenocarcinoma↗

PubMedDate not supplied

Islet allograft rejection in rats: a time course study characterizing adhesion molecule expression, MHC expression, and infiltrate immunophenotypes.

Wistar Furth (RT1u) islets transplanted under the renal capsules of streptozotocin-diabetic Lewis (RT1l) rats reject after 5-6 days of normoglycemia. Hand-picked WF islets (1500-2000) were transplanted under the kidney capsules of diabetic Lew or WF rats. Rats bearing iso- or allografts were killed on posttransplant days 2, 4, and 6. Serial frozen sections of grafts and controls were stained by immunoperoxidase for rat MAC-1, class II MHC, CD2, CD4, CD8, B-cells, VLA-4, LFA-1, L-selectin, ICAM-1, and VCAM-1. Infiltrating cells, parenchymal cells, and endothelial cells in five distinct compartments (i.e., peritoneal reflection, subcapsular perivascular space, islet grafts, graft-kidney interface, and kidney) were evaluated for expression of the various markers at each interval. Significant infiltrates arrived in three distinct waves in both iso- and allografts. First, macrophages blanketed the peritoneal capsular reflection and infiltrated by day 2. Second, the first wave of lymphocytes arrived in the edematous subcapsular soft tissue via capsular vessels by day 2 (allo > iso). Third, the second wave of lymphocytes arrived from the renal parenchyma to form a dense band at the graft-kidney interface and around grafts by days 4 and 6 (allo >>> iso); CD4+ cells vastly outnumbered CD8+ cells, with CD4+ cells being mobilized first and from interstitial vessels throughout the entire kidney. CD8+ cells emigrated only from renal interstitial vessels adjacent to the graft. Large numbers of L-selectin+, VLA-4+, and LFA-1+ cells were seen in the infiltrates with the most intensely staining cells being intravascular. B-cells composed a very small proportion of infiltrating cells in both allo- and isografts. Endothelial staining for ICAM-1 and VCAM-1 was prominent throughout. Both class II MHC and ICAM-1 expression were induced on renal tubular epithelial cells, but neither was found on islet parenchymal cells. In conclusion, this study shows that islet allograft rejection is more complex than previously realized.

Animals↗

PubMed2005

Effects of diabetes and hypertension on macrophage infiltration and matrix expansion in the rat kidney.

BACKGROUND: In experimental models of diabetes mellitus, aggravation of renal injury by concomitant hypertension has been described. Inflammatory mechanisms contribute to renal damage in both diseases. We investigated whether hypertension and diabetes mellitus act synergistically to induce macrophage infiltration and matrix expansion in the kidney. METHODS: Insulin-dependent diabetes mellitus was induced by streptozotocin injections to hypertensive mRen2-transgenic rats (TGR) and normotensive Sprague-Dawley control rats. Quantitative immunohistochemical examination of kidney tissue sections was used to measure macrophage infiltration and matrix expansion. The expression of MCP-1, Osteopontin, RANTES, ICAM-1 and VCAM-1 was evaluated by real-time RT-PCR. The localization of MCP-1 was studied by immunohistochemistry. RESULTS: Macrophage infiltration was present in the kidney of normotensive diabetic rats. Hypertensive rats exhibited a more marked infiltration of macrophages, regardless of whether diabetes was present or not. Gene expression of ICAM-1, VCAM-1 and RANTES was unaltered whereas Osteopontin and MCP-1 were induced by hypertension. Immunoreactive MCP-1 was slightly increased in diabetic rat kidney podocytes, and more markedly increased in hypertensive animals. Glomerular matrix accumulation was induced by diabetes and hypertension to a similar degree, and was highest in hypertensive, diabetic animals. CONCLUSION: Diabetes mellitus caused a mild, and angiotensin-dependent hypertension a more marked infiltration of macrophages in the kidney. Combination of both diseases led to additive effects on matrix expansion but not on inflammation. Hypertension appears to be a much stronger stimulus for inflammation of the kidney than STZ diabetes, at least in mRen2-transgenic rats.

Animals↗