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PubMed1997

Massive crystal-storing histiocytosis associated with low-grade malignant B-cell lymphoma of MALT-type of the parotid gland.

Massive crystal deposition is unusual in lymphoproliferative disorders. In this report, a mucosa-associated lymphoid tissue (MALT) low-grade B-cell lymphoma of the parotid gland containing large numbers of crystal-storing histiocytes is described. The patient, an 81-yr-old female, presented with a history of long-standing left parotid gland enlargement. FNA cytology of the tumor showed a lymphoplasmacytic infiltrate and sheets of large benign histiocytes with abundant eosinophilic intracytoplasmic inclusions. Paraffinsection immunohistochemistry performed on the cell block demonstrated that the histiocytic cells were immunoreactive for the KP-1 (CD-68) antibody and monotypic for cytoplasmic IGM and L-light chain. The cytological diagnosis was consistent with a low-grade B-cell lymphoma with plasmacytic differentiation associated with crystal-storing histiosis. A periparotid lymph node was biopsied and showed involvement by a monocytoid B-cell lymphoma with plasmacytic differentiation and crystal-storing histiocytosis in the pericapsular region.

Aged↗
PubMed1998

Isolated pleural effusion with hematopoietic cells of mixed lineage in a patient receiving granulocyte-colony-stimulating factor after high-dose chemotherapy.

A 43-yr-old woman with recently diagnosed breast carcinoma presented with a right pleural effusion after a cycle of adjuvant, high-dose chemotherapy supported by peripheral blood progenitor cells (PBPC) and granulocyte-colony-stimulating factor (G-CSF, Filgrastim). Cytologic examination of the pleural aspirate yielded highly cellular material composed predominantly of cells of myeloid and macrophage/monocytic lineages. Despite clinical concern of a malignant effusion, the combination of cytologic and immunophenotypic examination yielded the correct diagnosis of a nonneoplastic effusion related to underlying pleural inflammation and possibly the administration of G-CSF.

Adult↗
PubMed1998

Cytologic features of "dry-type" cutaneous leishmaniasis.

Exfoliative cytology smears from the lesions of 179 patients with cutaneous leishmaniasis due to Leishmania tropica were studied with specific reference to cellular reactions and their effect on the parasite. Aggregates of the parasite (so-called Leishmania Donovan bodies) were present within macrophages and in some fibroblasts. The nature of the inflammatory reaction to the disease was studied by performing differential counts of the inflammatory cells present in the smears. These were correlated with the number of Leishman Donovan bodies. There was an inverse relationship between the number of Leishman Donovan bodies and the percentage of small lymphocytes, neutrophils, and type I macrophages. It is postulated that aggregates of activated macrophages (designated types II and III) and the Leishmanian milieu (sticky matrix) protect the amastigote Leishmania parasites from being eradicated by the inflammatory and immune reaction. The cytoplasmic blebbing of the parasitophorous vacuoles and cell to cell connection of the activated histiocytes could be shown by the CD-68 immunostaining of the tissue biopsy.

Adolescent↗
PubMed1998

Transthoracic fine-needle aspiration cytology of inflammatory pseudotumor, fibrohistiocytic type: a case report with immunohistochemical studies.

Inflammatory pseudotumor, fibrohistiocytic type, also called benign fibrous histiocytoma, is a rare reactive entity usually found incidentally on routine chest roentgenography. We present a case of inflammatory pseudotumor, fibrohistiocytic type, initially diagnosed by fine-needle aspiration (FNA) cytology in a 39-yr-old woman with a history of breast carcinoma. Cytomorphologic characteristics were confirmed by a cell block examination and immunohistochemical findings. The differential diagnoses of the fine-needle aspiration cytology of this type of inflammatory pseudotumor are discussed.

Adult↗
PubMed1996

A novel technique for quantitative detection of mRNA expression in human bone derived cells cultured on biomaterials.

A nonisotopic and quantitative in situ hybridization technique was adapted to investigate the effect of biomaterials on the cellular expression of mRNA from human bone derived cells (HBD cells). HBD cells were cultured for 24 or 48 h on tissue culture plastic, alumina, and ion modified alumina. Osteocalcin, osteopontin, alkaline phosphatase, type I collagen alpha 1, and type I collagen alpha 2 mRNAs were quantified. Protein expression for collagen types I, III, and V, and for anti-human macrophages CD68 (DAKO-CD68, KP1) and CD68 (PG-M1), and anti-human myeloid/histiocyte antigen (DAKO-MAC 387) were determined immunohistochemically using monoclonal antibodies. At 24 and 48 h, levels of mRNA for alkaline phosphatase and osteonectin were greater than mRNA levels for osteopontin, osteocalcin, collagen type I alpha 1, and collagen type I alpha 2 for cells grown on the three substrata. However, at 48 h mRNA levels for alkaline phosphatase and osteonectin were significantly higher on the modified ceramic substrata relative to the native alumina. HBD cells appear to express CD68-KP1 when cultured for 24 h. The techniques provide a sensitive and reproducible assay to evaluate gene and protein expression of cells grown on different substrata.

Alkaline Phosphatase↗
PubMed1999

The characterization of macrophages and osteoclasts in tissues harvested from revised total hip prostheses.

The differentiation and maturation of macrophages and osteoclasts at the prosthetic interface in cases of implant loosening are poorly understood. Using histochemical and immunohistochemical staining methods, we compare macrophage differentiation in tissues from revised hip replacements in patients with specific clinical-radiological appearances. Periprosthetic tissues were harvested from 12 cemented acetabular and 12 cemented femoral components in 24 patients undergoing revision hip replacement. The prostheses were all radiographically and clinically loose. Six acetabular and six femoral components demonstrated radiographic ballooning osteolysis. Serial 6 microm frozen sections of the periprosthetic tissues were processed with hematoxylin and eosin for general tissue morphology, and analyzed for the presence of tartrate resistant acid phosphatase (TRAP, an osteoclast marker). Immunoperoxidase staining using monoclonal antibodies to CD68 (macrophages and osteoclasts) and CD51 (the alpha chain of the vitronectin receptor, an osteoclast marker) was also performed. Approximately 8-30% of the total cells in the tissues were positive for TRAP and the vitronectin receptor, and comprised a subset of the CD68 positive macrophages and macrophage polykaryons. However, there were no statistically significant differences between specific groups (femoral vs. acetabular, osteolysis vs. no osteolysis) for the numbers or percentages of macrophages or osteoclast-like cells. Once prosthetic loosening has occurred, few differences in the macrophage-osteoclast profile of tissues from different periprosthetic locations, with and without osteolysis, are noted. This suggests a final common biologic pathway for periprosthetic bone resorption, once implant loosening has transpired.

Acid Phosphatase↗
PubMedDate not supplied

The analysis of S100A9 and S100A8 expression in matched sets of macroscopically normal colon mucosa and colorectal carcinoma: the S100A9 and S100A8 positive cells underlie and invade tumor mass.

The expression of calcium-binding protein S100A9 was investigated in 23 matched sets of colorectal carcinoma and normal colon mucosa using two-dimensional gel electrophoresis. We found that, from a group of 23 patients, the level of S100A9 protein, in comparison with matched normal colon mucosa, was significantly increased in malignant tissues of 16 patients (70%). Furthermore, an additional protein, identified by matrix-assisted laser desorption/ionization - mass spectrometry (MALDI-MS) as S100A8, exhibited an increased expression in the same specimens of malignant tissues as the S100A9 protein. The immunohistological analysis revealed the accumulation of S100A9 positive cells, macrophages and polymorphonuclear leukocytes along the invasive margin of colorectal carcinoma. The S100A8 protein was found to be produced in the same location. The possible participation of both proteins and, especially, its heterodimeric complex calprotectin in colorectal carcinoma regression could be taken into account.

Antigens, CD↗
PubMed2001

Successful treatment of refractory anemia by high-dose methylprednisolone associated with an increment in CD68-positive cells in bone marrow.

Refractory anemia has a relatively low incidence of the subsequent development of acute leukemia and a relatively long survival among the myelodysplastic syndromes (MDS). We observed hematological improvement due to high-dose methylprednisolone in 9 of 18 patients with refractory anemia. The patients' age range was from 28 to 78 years old (mean age: 54), including 14 male and 4 females. A complete response was obtained in 5 patients, minimal response in 4 patients, and no response in 9 patients. Laboratory data of peripheral blood counts and differential counts of bone marrow aspirates were not different, except that fewer chromosomal abnormalities (P = 0.086) were observed in the responder group. Side effects were seen in two patients but were controllable. Overall survival was significantly longer in the responder group (Log-rank P = 0.040, Wilcoxon P = 0.045). The overall survival of responders did not reach the median and 85% of the patients were alive after 180 months, while the median overall survival of the nonresponders was 61.8 months. Disease progression was more frequently seen in the non-responder group (P = 0.045). Furthermore, we investigated retrospectively immunohistochemical bone marrow staining, and a significantly higher percentage of CD68-positive (22.6% +/- 7.1%) and CD45RA-positive cells was observed in the responder group compared to the non-responder group (6.5% +/- 1.3%). Our present results indicate that high-dose methylprednisolone is valuable as a primary treatment before other immunosuppressive treatments, because of its ease of use. High efficacy with high-dose methylprednisolone is expected, especially in patients in which increments in CD68-positive cells in bone marrow are observed.

Adult↗
PubMed2001

Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis: implications for pathogenesis.

The monocyte chemotactic proteins (MCPs) form a distinct structurally related subclass of C-C chemokines. MCPs select specific target cells due to binding to a distinct set of chemokine receptors and because of their effects on monocytes, and may participate in the process of granuloma formation during bacterial and/or mycobacterial infections. The aetiology of primary biliary cirrhosis (PBC) is still unclear, although bacterial infection and autoimmune processes have been implicated. In this study, the expression of three of the most potent monocyte chemoattractants, MCP-1, -2, and -3, was examined in patients with PBC and the data were compared with results for other liver diseases including primary sclerosing cholangitis (PSC), chronic viral hepatitis C, hepatic sarcoidosis, and normal liver. MCP-1 was expressed mainly in biliary epithelial cells of all liver specimens, irrespective of the cause of disease. Some mononuclear leukocytes in the portal tract expressed MCP-1 in all the disease groups examined and there were no significant differences in frequency between these groups. In contrast, more than 80% of PBC livers showed MCP-2- and MCP-3-positive mononuclear leukocyte infiltration in portal tracts, particularly around the bile ducts, whereas such cells were far less frequent in the other disease groups or in normal livers. Epithelioid granulomata of PBC patients contained MCP-2- and MCP-3-positive cells at their edge. In double staining experiments, more than 60% of the MCP-positive mononuclear cells co-expressed CD68, suggesting that a proportion of MCP-2- and MCP-3-positive cells are derived from monocytes. These monocytes expressing MCP-2 and MCP-3 may be responsible for the chemotactic activity of more monocytes. Such an expression pattern of MCP-1, -2 and -3 in portal tracts seems to be distinctive for PBC. This pattern underlines the importance of MCP-1, -2, and -3 in the recruitment of monocytes and possibly T lymphocytes into portal tracts, around the injured bile ducts, and into epithelioid granulomata in PBC. The data further implicate bacterial materials derived from bile in the overall pathogenesis of PBC.

Adult↗
PubMed1994

Dermatofibroma: superficial fibrous proliferation with reactive histiocytes. A multiple immunostaining analysis.

BACKGROUND: Dermatofibroma (DF) is a superficial form of benign fibrous histiocytoma, composed of a mixture of fibroblastic cells and histiocytic cells. The histogenesis of this lesion is a matter of controversy. METHODS: Forty-five cases of DF were investigated by single and multiple immunostaining techniques, using panel of 12 antibodies including proliferating cell nuclear antigen (PCNA), vimentin, and macrophage/histiocyte markers (HAM56 and CD68). RESULTS: Double immunostaining demonstrated that 58% of the DF cells simultaneously expressed PCNA and vimentin, whereas only 5% were PCNA+/HAM56+, and 2% were PCNA+/CD68+. By triple-stain for PCNA, vimentin, and HAM56, 56% of the DF cells were PCNA+/vimentin+/HAM56-, but only a few cells were PCNA+/HAM56+/vimentin+/-. Of the PCNA positive cells, 88% were vimentin+HAM56- and 10% were HAM56+ vimentin-/+. The cells positive for CD68 showed similar distribution to that of HAM56+ cells, though there were fewer of the former than the latter in most cases. These results suggest that the majority of the proliferating cells in DF express vimentin but not histiocytic markers. Morphologically, the PCNA+/vimentin+/HAM56- (or CD68-) cells exhibited a spindle-shaped configuration resembling fibroblasts, whereas most of the HAM56+/CD68+ cells possessed abundant rounded cytoplasm and were similar to normal histiocytes. CONCLUSIONS: The present study suggests that the proliferative compartment of DF cells is composed chiefly of mesenchymal/fibroblastic lineage, accompanied by varying numbers of normal reactive histiocytes.

Adolescent↗
PubMed1998

Asymptomatic synovitis precedes clinically manifest arthritis.

OBJECTIVE: It has been hypothesized that asymptomatic synovitis may precede clinical manifestations of arthritis in the earliest phase of rheumatoid arthritis (RA). To obtain more insight into this disease phase, we investigated the immunohistologic features of synovial tissue (ST) from the knee joints of rhesus monkeys with induced arthritis and from RA patients with both clinically involved and clinically uninvolved knee joints. METHODS: Serial ST biopsy specimens from the knee joints of 4 rhesus monkeys that had been immunized with type II collagen and ST from 10 RA patients were investigated. Eight patients without inflammatory joint disease served as controls. RESULTS: In ST from immunized monkeys, an influx of macrophages was observed well before the occurrence of arthritis. Signs of inflammation were also demonstrated in ST from clinically uninvolved knee joints of all RA patients evaluated. The ST was characterized in particular by infiltration with macrophages and by the expression of macrophage-derived cytokines. CONCLUSION: The findings support the view that asymptomatic synovitis precedes clinically manifest arthritis in both early and established RA. This implies that the debut of RA already represents a chronic phase of the disease.

Aged↗
PubMed1999

Expression of the activation antigen CD97 and its ligand CD55 in rheumatoid synovial tissue.

OBJECTIVE: Fibroblast-like synoviocytes (FLS) express decay-accelerating factor (CD55) at high levels. Recently, it was found that CD55 is a specific cellular ligand for the 7-span transmembrane receptor CD97. The objective of this study was to define the expression of this receptor-ligand pair in synovial tissue (ST) to provide more insight into the interaction between FLS and surrounding cells. METHODS: Antibodies against CD97 and CD55 were used for immunohistologic analysis of synovial biopsy specimens from 16 patients with rheumatoid arthritis (RA) and 15 patients with osteoarthritis (OA). In addition, an enzyme-linked immunosorbent assay system was used to determine the expression of soluble CD97 (sCD97) in synovial fluid (SF) from 30 patients with RA, 13 with OA, and 10 with reactive arthritis (ReA). RESULTS: In both RA and OA ST sections, strong expression of CD55 was confirmed on FLS in the intimal lining layer, where it was also found that all macrophages expressed CD97. The percentage of macrophages that expressed CD97 was lower in the synovial sublining (P = 0.005). The mean levels of sCD97 in SF were significantly higher in RA patients than in patients with OA or ReA (P < 0.0001). CONCLUSION: These results suggest that FLS are able to interact with macrophages via the CD97/CD55 receptor-ligand system. In this respect, the CD97/CD55 pair may account for the specific architecture of the intimal lining layer and may be of primary importance in maintaining and amplifying synovial inflammation. The specific increase in sCD97 levels in RA SF might be related to the presence of activated proteolytic systems or to the increase in synovial mass, rather than a consequence of local receptor-ligand interaction.

Adult↗
PubMed2000

Expression of osteopontin messenger RNA and protein in rheumatoid arthritis: effects of osteopontin on the release of collagenase 1 from articular chondrocytes and synovial fibroblasts.

OBJECTIVE: Osteopontin (OPN) is an extracellular matrix protein that has been implicated in the interactions between tumor cells and host matrix, including those involved in invasion and spread of tumor cells. Because joint destruction in rheumatoid arthritis (RA) is mediated by the invasive growth of synovial tissue through its attachment to cartilage, we examined the expression of OPN in the synovia of patients with RA and the effect of OPN on the production of collagenase 1 in rheumatoid synovial fibroblasts and articular chondrocytes. METHODS: The expression of OPN messenger RNA (mRNA) and protein in synovia from 10 RA patients was examined by in situ hybridization and immunohistochemistry. Synovial fibroblasts from RA patients and articular chondrocytes from patients without joint disease were cultured in the presence of various concentrations of OPN, and levels of collagenase 1 in the culture supernatants were measured by enzyme-linked immunosorbent assay. RESULTS: The expression of OPN mRNA and protein was observed in 9 of 10 specimens obtained from patients with RA. OPN was expressed in the synovial lining and sublining layer and at the interface of cartilage and invading synovium. Double labeling revealed that the majority of OPN-expressing cells were positive for the fibroblast-specific enzyme prolyl 4-hydroxylase and negative for the macrophage marker CD68, while only a few, single OPN-expressing cells were positive for CD68 at sites of synovial invasion into cartilage. OPN staining was not observed in lymphocytic infiltrates or leukocyte common antigen (CD45)-positive cells. Three of 3 cultures of human articular chondrocytes secreted detectable basal amounts of collagenase, with a dose-dependent increase upon OPN stimulation, while synovial fibroblast cultures produced much lower levels of collagenase, with only 2 of 4 fibroblast cultures responding in a dose-dependent manner. CONCLUSION: These findings suggest that OPN produced by synovial fibroblasts in the synovial lining layer and at sites of cartilage invasion not only mediates attachment of these cells to cartilage, but also contributes to matrix degradation in RA by stimulating the secretion of collagenase 1 in articular chondrocytes.

Aged↗
PubMed2001

Localization of 3-nitrotyrosine to rheumatoid and normal synovium.

OBJECTIVE: To determine the localization of 3-nitrotyrosine (3-NT), a footprint marker of peroxynitrite (ONOO-) and other reactive nitrogen species, to the inflamed human synovium and to compare this with normal synovial and nonsynovial tissue of human and animal origin. METHODS: Monoclonal and polyclonal antibodies were used to investigate for 3-NT, inducible nitric oxide synthase (iNOS), macrophage marker CD68, and the vascular smooth muscle marker alpha-actin by avidin-biotin immunocytochemistry. RESULTS: In the inflamed synovium, 3-NT was found in the vascular smooth muscle and macrophages. In normal human synovium, 3-NT was present in the vascular smooth muscle and some lining cells and was not associated with immunoreactivity for iNOS. Similarly, 3-NT could be demonstrated in the vascular smooth muscle cells of normal rats and iNOS knockout mice. It was not present in the vascular smooth muscle of healthy, nonsynovial tissue. CONCLUSION: The synovial vasculature in histologically normal human and naive rodent synovium was alone among the normal tissues studied in exhibiting iNOS-independent immunoreactivity for 3-NT. These findings suggest a physiologic role for ONOO- in normal synovial vascular function.

Actins↗
PubMed2001

Predominance of Th1 immune response in diffuse proliferative lupus nephritis.

OBJECTIVE: Lupus nephritis, which shows various histologic patterns, is a serious complication of systemic lupus erythematosus (SLE). We previously demonstrated the importance of Thl cell-mediated immune response in patients with diffuse proliferative lupus nephritis (DPLN). The aim of this study was to examine the relationship between the peripheral blood Th1/Th2 balance and the intrarenal immune response. METHODS: The Th1:Th2 ratio in peripheral blood was measured by intracellular staining for cytokines with flow cytometry. Immunohistochemical analysis of renal biopsy specimens was performed to clarify the characterization of local infiltrating cells in 3 groups of subjects: SLE patients with World Health Organization (WHO) class IV nephritis (DPLN) (group I; n = 13), SLE patients with WHO class V nephritis (group II; n = 9), and patients with minor glomerular lesions (group III; n = 7). In addition, the histologic activity index and chronicity index were evaluated and correlated with the Th1:Th2 ratio. RESULTS: Immunohistochemical studies showed higher numbers of CD68+ macrophages, CD3 + T cells, and interferon-gamma-positive cells in group I than in groups II or III. Renal tissues from patients in group I also showed up-regulation of expression of osteopontin and CD40, with a small number of infiltrating T cells expressing interleukin-4. Overall, the Thl:Th2 ratio in group I patients (SLE with DPLN) was high and correlated significantly with the histologic activity index, but not with the chronicity index. CONCLUSION: We have identified a predominance of Thl-type response in both peripheral and renal tissues of patients with DPLN, suggesting that the peripheral blood Thl:Th2 ratio directly reflects the local histopathologic findings. In patients with lupus nephritis, the peripheral blood Th1:Th2 ratio could be useful as a parameter that reflects the renal histologic activity or the strength of the local Thl response.

Adult↗
PubMed2001

Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions.

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that causes motor, sensory, and cognitive deficits. The present study characterized demyelinated lesions in the cerebral cortex of MS patients. One hundred twelve cortical lesions were identified in 110 tissue blocks from 50 MS patients. Three patterns of cortical demyelination were identified: Type I lesions were contiguous with subcortical white matter lesions; Type II lesions were small, confined to the cortex, and often perivascular; Type III lesions extended from the pial surface to cortical layer 3 or 4. Inflammation and neuronal pathology were studied in tissue from 8 and 7 patients, respectively. Compared to white matter lesions, cortical lesions contained 13 times fewer CD3-positive lymphocytes (195 vs 2,596/mm3 of tissue) and 6 times fewer CD68-positive microglia/macrophages (11,948 vs 67,956/mm3 of tissue). Transected neurites (both axons and dendrites) occurred at a density of 4,119/mm3 in active cortical lesions, 1,107/mm3 in chronic active cortical lesions, 25/mm3 in chronic inactive cortical lesions, 8/mm3 in myelinated MS cortex, and 1/mm3 in control cortex. In active and chronic active cortical lesions, activated microglia closely apposed and ensheathed apical dendrites, neurites, and neuronal perikarya. In addition, apoptotic neurons were increased significantly in demyelinated cortex compared to myelinated cortex. These data support the hypothesis that demyelination, axonal transection, dendritic transection, and apoptotic loss of neurons in the cerebral cortex contribute to neurological dysfunction in MS patients.

Adolescent↗
PubMed1994

Distribution of macrophages in the mouse uterus from one day to three months after parturition, as defined by the immunohistochemical localization of the macrophage-restricted antigens F4/80 and macrosialin.

BACKGROUND: The morphology of placental detachment sites and the distribution of macrophages were studied in the mouse uterus from day 1 to 3 months post partum. METHODS: Uterine morphology was studied using H&E and Mallory's Trichrome staining. Macrophages were identified using the macrophage-restricted antigens F4/80 and FA/11 and the leukocyte beta 2-integrin CR3 (Mac-1) which is also expressed by neutrophils. RESULTS: The post-partum wound was infiltrated by large numbers of CR3+ F4/80+ FA/11+ macrophages, and CR3+ neutrophils. The wound resolved rapidly and no inflammatory infiltrate or necrotic tissue was seen by day 5 post partum. The area of the detachment wound and the site of the metrial gland of pregnancy resolved into a structure, here called a post-partum nodule, which persisted for at least three months. The post-partum nodule consisted of an outer layer of collagen around a group of nodule-specific cells which could be divided into haemosiderin- and lipid-bearing phenotypes. The lipid-bearing nodule cells were not found after day 20 post partum. Nodule cells were FA/11+ at all times and also expressed leukocyte common antigen. Expression of CR3 and F4/80 was found on nodule cells up to day 9-10 post partum. CR3 expression was found only occasionally after day 10. F4/80 expression was downregulated from day 9-10 to day 20 but was found consistently after day 20. Implantations of second and subsequent pregnancies are known not to occur in the immediate vicinity of post-partum nodules and nodules from successive pregnancies were seen to be separate within the uterus. CONCLUSIONS: Since the endometrial area in the immediate vicinity of nodules is inimical to implantation and nodules consist of a group of macrophages, it can be implied that nodule macrophages are exerting some influence on the endometrium in their vicinity.

Animals↗