bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microscopic colitis with giant cells
Authors: Libbrecht L , Croes R , Ectors N , Staels F , Geboes K 
Published: March 2003

Microscopic colitis with giant cells Aims: Collagenous colitis and lymphocytic colitis are the two types of microscopic colitis with specific morphological features. In this report we describe a new histopathological subtype of microscopic colitis. Methods and results: Colonoscopy in four patients with chronic watery diarrhoea showed no macroscopic abnormalities. The random biopsies from the colon showed subepithelial multinucleated giant cells in combination with the features of collagenous colitis in three patients and lymphocytic colitis in one patient. These multinucleated giant cells were positive for CD68. The density of macrophages was highest in the most superficial part of the lamina propria. In one patient, a previous biopsy showed features consistent with collagenous colitis without multinucleated giant cells. Treatment with budesonide led to the disappearance of diarrhoea in all four patients. Conclusions: The clinical and histopathological features of the four presented patients indicate that there exists a histopathological subtype of microscopic colitis characterized by the presence of subepithelial multinucleated giant cells, which probably arise from fusion of subepithelial macrophages. Analysis of more patients with this histopathological subtype of microscopic colitis is necessary to determine whether they also form a clinically distinct group.
Clinicopathological prognostic factors in soft tissue leiomyosarcoma: a multivariate analysis
Authors: Miyajima K , Oda Y , Oshiro Y , Tamiya S , Kinukawa N , Masuda K , Tsuneyoshi M 
Published: March 2003

Clinicopathological prognostic factors in soft tissue leiomyosarcoma: a multivariate analysis Aims: Prognostic factors affecting survival in cases of leiomyosarcoma of soft parts were investigated in this study. Methods and results: A retrospective study of 267 patients was carried out. This group comprised 142 females (53%) and 125 males (47%), whose ages ranged from 7 to 95 years (median 58 years). One hundred and five cases were superficially situated (arising from the skin or subcutis), while the remaining 162 cases were deeply situated (subfacial). Nineteen were cases of pleomorphic leiomyosarcoma where the diagnosis had been amended from malignant fibrous histiocytoma to leiomyosarcoma whilst under review. Of the 167 patients with follow‐up data, 83 died of leiomyosarcoma. In univariate analysis, depth, tumour size (≥50 mm), mitotic rate of >20 per 10 high‐power fields (HPF), tumour necrosis of >50% and a high stage according to the most recent American Joint Committee on Cancer (AJCC) staging for soft tissue sarcoma were found to lessen significantly the rate of survival (log rank test; P < 0.05). However, in multivariate analysis (Cox's proportional hazards model), tumour size and high AJCC stage were the only factors that were correlated independently with decreased survival. Conclusions: This study indicates that the most reliable prognostic parameters are tumour size and AJCC stage in leiomyosarcoma.
Intraepidermal cytokeratin 7 immunoreactive cells in the non‐neoplastic nipple may represent interepithelial extension of lactiferous duct cells
Authors: Yao D X , Hoda S A , Chiu A , Ying L , Rosen P P 
Published: March 2003

Intraepidermal cytokeratin 7 immunoreactive cells in the non‐neoplastic nipple may represent interepithelial extension of lactiferous duct cells Aims: The interpretation of cytokeratin 7 (CK7)‐positive cells in the epidermis of the nipple has been controversial. These cells have been described in Paget's disease of the nipple, and they have also been cited as benign `Toker' cells or as Merkel cells. Having observed CK7+ cells in histologically unremarkable nipple biopsies, we sought to assess the distribution of CK7+ cells in Paget's disease of the nipple and in histologically unremarkable nipple. Methods and results: Representative sections from 37 cases of Paget's disease of the nipple and 32 cases of histologically unremarkable nipple were obtained. The histologically unremarkable nipple sections were taken from prophylactic mastectomies (n=17) and from autopsies of patients who did not have breast cancer (n=15). CK7 immunostaining was performed on sections from formalin‐fixed paraffin blocks. Sequential sections were immunostained with antibodies to low‐molecular weight cytokeratin‐CAM 5.2 and HER‐2/neu. CK7+ cells were present in the epidermis around the opening of the lactiferous ducts in Paget's disease (95%) and in histologically unremarkable nipple (45%) cases. CK7+ cells diminished in number with increasing distance from the orifice of the lactiferous ducts. The lactiferous duct epithelium in Paget's disease and in histologically unremarkable nipple was CK7+ in all specimens when this element was present. CAM5.2 immunostaining had a similar but weaker pattern of reactivity. HER‐2/neu reactivity was seen in 68% cases of Paget's disease and was negative in all cases of histologically unremarkable nipple. Tumour cells in two cases of Paget's disease were CK7−. In one of these, the underlying breast carcinoma was also CK7−, the only CK7− tumour in this series. In the other case, the normal lactiferous duct was CK7+ and no underlying carcinomatous tissue was available to study. Conclusions: The presence of CK7+ cells does not equate to Paget's disease of the nipple. Intraepidermal CK7+ cells in the non‐neoplastic nipple can be a manifestation of interepithelial extension of benign lactiferous duct cells. The increased presence of CK7+ cells in Paget's disease probably results either from neoplastic transformation of native intraepithelial lactiferous duct cells or form direct extension/migration of neoplastic cells into the nipple. The distribution of CK7 immunoreactive cells in the nipple epidermis can be helpful in the diagnosis of Paget's disease of the nipple.
Sinonasal haemangiopericytoma‐like tumour: a sinonasal glomus tumour or a haemangiopericytoma?
Authors: Tse L L Y , Chan J K C 
Published: March 2003

Sinonasal haemangiopericytoma‐like tumour: a sinonasal glomus tumour or a haemangiopericytoma? Aims: Sinonasal haemangiopericytoma‐like tumour is controversial with regard to its nosologic nature. This study aims to investigate its relationship with glomus tumour and haemangiopericytoma. Methods and results: Six cases of sinonasal haemangiopericytoma‐like tumours identified in our files were reviewed for clinicopathological features, and compared with five cases each of soft tissue glomus tumour and meningeal haemangiopericytoma. Immunohistochemical studies for muscle‐specific actin, smooth muscle actin, desmin and CD34 were performed. Sinonasal haemangiopericytoma‐like tumour demonstrated a uniform histological appearance with bland‐looking short, spindly cells forming sheets and short fascicles. The tumour cells were interspersed with slit‐like, round and ectatic blood vessels. Actin immunoreactivity was demonstrated in all six cases, although occasionally patchy. The histological appearance and immunohistochemical phenotype of sinonasal haemangiopericytoma‐like tumour were very similar to and focally indistinguishable from glomus tumour. Meningeal haemangiopericytoma, in contrast, was characterized by high tumour cellularity, random nuclear orientation, presence of staghorn vasculature and lack of immunohistochemical evidence of myogenic differentiation. Conclusions: We conclude that sinonasal haemangiopericytoma‐like tumour is biologically close to or identical to glomus tumour, but is not related to haemangiopericytoma.
Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma
Authors: Mathers M E , Pollock A M , Marsh C , O'Donnell M 
Published: March 2003

Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma Aims: The histopathological diagnosis of chromophobe renal cell carcinoma can present a diagnostic challenge, as these tumours can resemble either conventional renal cell carcinoma or oncocytoma. The aim of this study was to determine whether cytokeratin 7 expression is of practical use in the distinction of these three entities. Methods and results: A total of 40 cases previously diagnosed as either chromophobe renal cell carcinoma, conventional renal cell carcinoma or oncocytoma were identified. A representative section of each was stained with H&E and cytokeratin 7. Following independent review of the cases by three pathologists, a consensus diagnosis for each case was reached and the pattern of cytokeratin 7 staining was assessed. There were 12 cases of chromophobe renal cell carcinoma in the study, all of which showed a characteristic peripheral membrane pattern of staining for cytokeratin 7. Seventeen of the 18 cases of conventional renal cell carcinoma studied were negative for cytokeratin 7, while one case showed weak focal staining of <5% of the cells. The 10 cases of oncocytoma showed patchy weak to moderate cytoplasmic expression of cytokeratin 7, without the characteristic peripheral membrane accentuation seen in the chromophobe carcinomas. Conclusions: Immunohistochemical staining for cytokeratin 7 appears to be a useful adjunct in the diagnosis of chromophobe renal cell carcinoma, and in distinguishing this tumour from both oncocytoma and conventional renal cell carcinoma.
Extrauterine placental site trophoblastic tumour in association with a lithopedion
Authors: El Hag I A , Ramesh K , Kollur S M , Salem M 
Published: March 2003

Aim:  We describe an unusual case of extrauterine placental site trophoblastic tumour located in pouch of Douglas in association with a lithopedion.Methods and results:  A 35‐year‐old female presented with acute abdomen and peritonitis following rectal perforation. The patient gave a history of 5 months amenorrhoea followed by vaginal bleeding 5 years prior to admission. At laparotomy, a lithopedion was found in pouch of Douglas with rectal perforation and peritonitis. The lithopedion was removed, rectal perforation was sutured and a colostomy was performed. The colostomy was closed later and tumour was seen in the colostomy wound as well as attached to the lithopedion removed previously. The patient presented with a repeated episode of rectal perforation and the tumour had spread to colon, small intestine, omentum, mesentery and right ovary.Conclusion:  A high‐grade malignant placental site trophoblastic tumour with aggressive clinical course occurred at an extrauterine site. It complicated calcified abdominal pregnancy and resulted in repeated rectal perforation and peritonitis.
High expression of markers of apoptosis in Langerhans cell histiocytosis
Authors: Petersen B L , Rengtved P , Bank M I , Carstensen H 
Published: March 2003

Aims:  Langerhans cell histiocytosis is a rare disease with clonal proliferation of dendritic histiocytes, occurring most frequently in infancy and early childhood. In the localized form (single system), the disease is self‐limiting, but in the cases of multisystem disease a third of the patients develop organ dysfunction. In these cases the prognosis is poor. Our objective has been to study the immunohistochemical expression of Fas and Fas‐ligand (Fas‐L) in order to determine whether the level of expression of these proteins could predict the outcome of the disease. We also wanted to determine the number of apoptotic cells to compare with the expression of Fas and Fas‐L.Methods and results:  We analysed the expression of Fas and Fas‐L in 76 infiltrates from 49 paediatric patients with Langerhans cell histiocytosis. We also compared the results with the expression of the tumour suppressor protein p53 and the number of cells in apoptosis detected with TUNEL. Langerhans cell histiocytosis cells showed strong expression of p53 and in some cases co‐expression of Fas and Fas‐L. The expression of Fas‐L was significantly higher in infiltrates from patients with single‐system disease. The actual number of pathological Langerhans cells in apoptosis as estimated by TUNEL was low.Conclusions:  The low number of TUNEL‐reactive cells can be explained by the rapid turnover of apoptotic cells in the tissue, not leaving the apoptotic cells long enough in the tissue to be detected. The co‐expression of Fas and Fas‐L in some Langerhans cells can lead to an autocrine apoptotic shortcut, mediating the death of the double‐positive cells. Our findings suggest that apoptosis mediated through the Fas/Fas‐L pathway may contribute to the spontaneous regression of lesions in single‐system disease. A delicate balance between autocrine death and survival of Langerhans cells may have been disturbed in patients with multisystem lesions.
Exploring the feasibility of an anti‐idiotypic cocaine vaccine: analysis of the specificity of anticocaine antibodies (Ab1) capable of inducing Ab2βanti‐idiotypic antibodies
Authors: Schabacker D. S. , Kirschbaum K. S. , Segre M. 
Published: March 2003

SummaryConventional vaccination with the cocaine molecule conjugated to a protein carrier is a new approach in the treatment of addiction. Experimentally, this strategy has been shown to alter the pharmacokinetics as well as the psychostimulant effect of a cocaine challenge. The purpose of this study was to investigate whether a more stable and less controversial molecule, an anti‐idiotypic antibody, which mimics the configuration of the cocaine molecule (Ab2β), could be successfully used instead of cocaine. Two cocaine conjugates that presented different areas of the cocaine molecule to the immune system were used to produce monoclonal antibodies specific for cocaine (Ab1). Several anti‐idiotypic antibodies were then produced. Four were identified as Ab2β, or internal images of the antigen; when injected into BALB/c mice, they elicited an anticocaine response. The anticocaine response elicited by one of the four Ab2β (K1–4c) was sufficient to significantly reduce the level of cocaine that targeted the brain following cocaine challenge, compared with the level of cocaine found in the brain of control animals immunized with irrelevant antibody. In conclusion, the possibility of an anti‐idiotypic vaccine seems to be worth pursuing.
Regulation of T‐cell apoptosis: a mixed lymphocyte reaction model
Authors: O'flaherty E. , Wong W.‐K. , Pettit S. J. , Seymour K. , Ali S. , Kirby J. A. 
Published: March 2003

SummaryDespite the capacity for antigen‐specific activation and rapid clonal expansion, homeostatic mechanisms ensure that the mature immune system contains a relatively stable number of T cells. In recent years, it has become apparent that this stability is a consequence of apoptotic death of most of the specific T cells generated during an immune response. Clearly this process must be tightly regulated in order to retain sufficient T‐cell progeny to mediate an effective response, whilst allowing the rapid deletion of these cells at the end of the response to prevent lymphadenopathy and cross‐reactive autoimmunity. In this study, the factors that regulate the sensitivity of T cells to apoptosis were investigated in vitro after the induction of primary T‐cell activation within a mixed lymphocyte reaction (MLR). It was found that activated T cells rapidly acquire the expression of both Fas and Fas ligand (FasL) on their surface and contain high levels of the precursor form of the pro‐apoptotic enzyme, caspase 8 (FLICE). However, these T cells were resistant for up to 5 days to apoptosis following the stimulation of Fas; a maximal apoptotic response was observed after 7 days. This time point coincided with a marked reduction in expression of the FLICE inhibitory protein (FLIP) and maximal activity of caspase 8. At time points beyond day 7, the number of viable cells in the MLR decreased further despite a reduction in the expression of FasL. However, the expression of interleukin‐2 (IL‐2) at these late time points was low, resulting in a decrease in expression of the anti‐apoptotic protein Bcl‐2. This can produce apoptosis by allowing leakage of cytochrome‐c from mitochondria resulting in direct activation of the caspase cascade. In this study, it is shown that T cells are resistant to apoptosis for the first 5 days after activation as a consequence of insensitivity of the Fas pathway and the presence of intracellular Bcl‐2. After between 5 and 7 days, the cells become sensitive to Fas‐mediated apoptosis while retaining Bcl‐2 expression. At later time points, Fas ligation is reduced but the cells respond to a decreased availability of IL‐2 by reducing Bcl‐2 expression; this encourages further apoptosis by allowing the direct activation of caspase enzymes.
Mechanisms of pertussis toxin‐induced myelomonocytic cell adhesion: role of CD14 and urokinase receptor
Authors: Li H. , Wong W. S. F. 
Published: March 2003

SummaryPertussis toxin (PTX) has been shown previously to promote myelomonocytic cell adhesion in serum. The aim of the present study was to identify, using transforming growth factor‐β1 and 1,25‐(OH)2 vitamin D3 (TGF‐β1/D3)‐primed U937 cells, the PTX‐binding site(s) and the adhesion molecule(s) responsible for PTX‐induced myelomonocytic cell adhesion. Monoclonal antibodies (mAbs) directed against CD14, CD11b, CD18 or urokinase receptor (uPAR) significantly inhibited PTX‐induced primed U937 cell adhesion in serum in a concentration‐dependent manner. However, only anti‐CD14 and anti‐CD18 mAbs were able to prevent the myeloid cells from binding to PTX‐coated plates and significantly inhibited a PTX‐induced rise of [Ca2+]i in primed U937 cells. A receptor‐isolation study showed that biotinylated PTX recognized a 48 000‐molecular weight protein in primed U937 cell lysates, which could be specifically blocked by excess unlabelled PTX or by anti‐CD14 mAb. On the other hand, mAb directed against uPAR significantly blocked PTX‐induced myeloid cell adhesion to serum and to immobilized vitronectin, a major extracellular matrix protein in serum. Taken together, our data suggest that PTX may bind to cell‐surface CD14 to induce myelomonocytic cell adhesion to vitronectin in serum via uPAR activation, which may represent a pathogenetic mechanism for the respiratory tract infection induced by Bordetella pertussis.
Human and rodent decay‐accelerating factors (CD55) are not species restricted in their complement‐inhibiting activities
Authors: Harris C. L. , Spiller O. B. , Morgan B. P. 
Published: March 2003

SummaryHomologous complement activation is restricted on cells by the complement regulators, decay‐accelerating factor (DAF), membrane cofactor protein (MCP) and CD59. These proteins act in concert with other membrane structures to protect cells from homologous complement attack. In contrast, cells are usually sensitive to heterologous complement attack. It has been suggested that species‐specific restriction of complement activation can be attributed to the inability of regulators to inhibit across species. We have investigated the capacities of human, rat and mouse analogues of DAF to regulate homologous and heterologous complement. Cells transfected with cDNA encoding these analogues were protected from heterologous complement attack. C3b‐deposition experiments indicated that whilst cells were best protected by DAF from the same species, all three analogues inhibited human, rat and mouse complement. Comparable results were obtained in haemolysis assays using soluble, recombinant forms of the proteins. Inhibition of the classical pathway (CP) was best achieved with homologous DAF, although human DAF also inhibited rat complement, rat DAF also inhibited human complement and mouse DAF inhibited complement from all species. Human DAF was the best inhibitor of alternative pathway (AP)‐mediated attack, inhibiting complement from all species. Mouse DAF inhibited mouse and rat AP, whilst rat DAF inhibited only rat AP. These data indicate that human and rodent analogues of DAF are not species restricted and highlights interesting differences in the capacity to regulate AP and CP. This has implications in broader fields of research, such as xenotransplantation, where cross‐species regulation of complement is of paramount importance.
T lymphocytes from granulocyte colony‐stimulating factor–/– mice produce large quantities of interferon‐γ in a chronic infection model
Authors: Mannering S. I. , Zhan Y. , Gilbertson B. , Lieschke G. J. , Cheers C. 
Published: March 2003

SummaryLittle is known about the role of granulocyte colony‐stimulating factor (G‐CSF) in the response to chronic bacterial infections. To address this we infected G‐CSF knock out (G‐CSF–/–) mice with Mycobacterium avium. Infection was not exacerbated in G‐CSF–/– mice despite a deficiency in the total bone marrow cells, colony‐forming haemopoietic cells, granulocytes and monocyte precursors in the bone marrow. Peritoneal cells from G‐CSF–/– produced less nitric oxide (NO) upon culture in vitro with antigen than did wild‐type (WT) cells. Unexpectedly, T cells from infected G‐CSF–/– mice were able to produce significantly more interferon‐γ (IFN‐γ) than the wild type (WT) controls. T cells from G‐CSF–/– mice still produced more IFN‐γ even when in vitro NO production was inhibited, while enzyme‐linked immunospot assay (ELISPOT) assays showed more IFN‐γ‐producing cells in the G‐CSF–/– mice. This was confirmed by intracellular cytokine staining (ICCS), which showed that there were more IFN‐γ producing T cells in vivo in the G‐CSF–/– than the WT controls following M. avium infection. It is possible that a deficit of NO in vivo allows T cells to develop a higher IFN‐γ‐producing phenotype. Thus we show a novel relationship between G‐CSF and IFN‐γ production by T cells revealed in this chronic bacterial infection model.
Reversal of ultraviolet radiation‐induced immune suppression by recombinant interleukin‐12: suppression of cytokine production
Authors: Schmitt D. A. , Walterscheid J. P. , Ullrich S. E. 
Published: March 2003

SummaryExposure to ultraviolet (UV) radiation, a complete carcinogen, suppresses the immune response. Data from a number of laboratories have indicated that one consequence of UV exposure is suppressed T helper type 1 (Th1) cell function with normal Th2 cell activation, resulting in a shift to a Th2‐like phenotype. The reversal of UV‐induced immune suppression and tolerance induction by recombinant interleukin‐12 (rIL‐12) supports this observation. The focus of this study was to determine the mechanism(s) by which rIL‐12 reverses UV‐induced immune suppression. Two possibilities were considered: up‐regulation of interferon‐γ (IFN‐γ) secretion by rIL‐12 and suppression of UV‐induced cytokine secretion by rIL‐12. To our surprise we found that the ability of rIL‐12 to overcome UV‐induced immune suppression was independent of its ability to up‐regulate IFN‐γ secretion. Rather, rIL‐12 suppressed the production of cytokines that are known to be important in UV‐induced immune suppression. Injecting UV‐irradiated mice with rIL‐12, or adding rIL‐12 to UV‐irradiated keratinocyte cultures suppressed IL‐10 secretion, in part by affecting the transcription of the IL‐10 gene. Furthermore, we found that rIL‐12 suppressed UV‐induced tumour necrosis factor‐α (TNF‐α) production. Because IL‐10 is involved in the UV‐induced suppression of delayed‐type hypersensitivity and TNF‐α in the UV‐induced suppression of contact allergy, these findings provide a mechanism to explain how rIL‐12 overcomes UV‐induced immune suppression in these related but different immune reactions. In addition, they suggest a novel mechanism by which rIL‐12 alters immune reactivity, direct suppression of cytokine secretion induced by UV radiation.