bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of frozen section diagnoses of breast lesions after introduction of a national programme in mammographic screening
Authors: Scheiden R , Sand J , Tanous A M , Knolle U , Capesius C , Wagnon M Ch , Faverly D 
Published: March 2003

Accuracy of frozen section diagnoses of breast lesions after introduction of a national programme in mammographic screening Aims: By introducing mammography screening programmes, the size of the detected breast lesions became smaller and the histopathological interpretation problems greater. The study’s aim was to analyse the risks and possible limitations of the frozen section method. Methods and results: Frozen section consultations of breast lesions (n=559) 2 years before and 6 years after launching a national mammographic screening programme in 1992 were evaluated in regard of the benign/malignant ratio, tumour size, preoperative frozen section results and final permanent section diagnoses. The breast frozen section examinations of 1990 compared with those from 1998 declined from 70.7% (299/423) to 62.2% (260/418) (P < 0.01), the benign/malignant ratio from 1.09 to 0.54 (P < 0.0001), the rate of the conclusive, correct frozen section diagnoses from 96.3% to 91.9% (P < 0.03). The sensitivity dropped from 92.3% to 87.6%, the negative predictive value from 95.7% to 88.3%, whereas the negative likelihood ratio rose from 0.08 to 0.12. The ‘small’ (≤ 10 mm) invasive breast carcinomas increased from 14.2% to 22.3% (P < 0.01) and the ‘in situ’ carcinomas from 2.1% to 6.6% (P < 0.05). Conclusions: The declining sizes of breast tumours (≤ 10 mm), especially from radiologically detected lesions and sometimes without a macroscopic correlate, create new limitations and changing indications in the histopathological interpretation. Considering the performance of new diagnostic methods (i.e. large core needle biopsies), frozen sections of surgical specimens should not be the primary diagnostic procedure for breast lesions and should be performed only after other preoperative methods have failed.
Pedunculated peritoneal surface polyps in pseudomyxoma peritonei syndrome
Authors: Sugarbaker P H , Yan H , Shmookler B 
Published: March 2003

Pedunculated peritoneal surface polyps in pseudomyxoma peritonei syndrome Aims: Pseudomyxoma peritonei syndrome is a rare disease that originates from an adenomatous lesion of the appendix that, from pressure, perforates to gain access to the free peritoneal cavity. The relative sparing of the small bowel surfaces allows for complete cytoreduction even though many kilograms of mucinous tumour exist at other sites within the abdomen and pelvis. The purpose of this study was to examine the mechanism whereby the small bowel remains free of gross tumour and peritoneal surface polyps form. Methods and results: Peritoneal surface polyps were harvested and examined grossly and histologically. A hypothesis for their formation on small bowel and small bowel mesentery was proposed. Polyps are known to be associated with repeated motion of enteric contents moving past adenomatous tissue so that, over time, an elongated stalk is created. We have repeatedly observed pedunculated polyps on the peritoneal surface of the small bowel in patients with pseudomyxoma peritonei syndrome. No other site within the peritoneal cavity has had a pseudomyxoma polyp located upon its surface. Conclusions: The peristaltic motion of the small bowel causes adherent adenomatous tissue to develop a stalk on the peritoneal surface. Motion not only creates polypoid lesions but also repeatedly clears mucinous tumour cells from the small bowel surface. With pseudomyxoma peritonei and with other types of cancerous dissemination, prevention of adherence by motion may interfere with the implantation of malignant cells.
CD9 immunohistochemical staining of breast carcinoma: unlikely to provide useful prognostic information for routine use*
Authors: Jamil F , Peston D , Shousha S 
Published: March 2003

CD9 immunohistochemical staining of breast carcinoma: unlikely to provide useful prognostic information for routine use Aims: CD9, a cell membrane glycoprotein, is found in a variety of tumour cells and is believed to regulate cell motility and possibly cell growth. It has been reported that the absence of CD9 is associated with increased aggressiveness of breast carcinoma, but no detailed studies of the distribution of CD9 in normal and abnormal breast tissue are available. This investigation was aimed at studying the distribution of CD9 in a wide variety of breast biopsies including normal, benign, and malignant cases, and assessing its usefulness as a prognostic marker in breast cancer. Methods and results: Sections of 113 breast biopsies from female and male patients including 10 normal, 23 benign, and 80 malignant cases were examined. The monoclonal antibody CD9 (Novacastra Ltd, Newcastle‐upon‐Tyne, UK) was used with the avidin–biotin complex immunoperoxidase technique. The results were assessed semiquantitatively using a four scale system of 3+, 2+, 1+ and negative. All normal and benign epithelial cells were strongly stained (3+). In female breast carcinomas, 40% were 3+, 49% were 2+, and 11% were 1+. Both cases of male breast carcinomas scored 3+. For female breast cancers, the results were then correlated to tumour grade, the presence or absence of lymph node metastases, and oestrogen and progesterone receptor status. No significant statistical correlation was found with any of these parameters. We then examined 11 axillary lymph nodes with metastases from some of the above cases. Three of these cases had a CD9 score of 3+, seven were 2+, and one was 1+. The metastatic tumours in all 11 cases were strongly stained (3+). Conclusions: Immunostaining for CD9 is unlikely to provide any useful additional prognostic information for clinical purposes.
Photoreceptor cell differentiation in retinoblastoma demonstrated by a new immunohistochemical marker mucin‐like glycoprotein associated with photoreceptor cells (MLGAPC)
Authors: Tsuji M , Goto M , Uehara F , Kaneko A , Sawai J , Yonezawa S , Ohba N 
Published: March 2003

Photoreceptor cell differentiation in retinoblastoma demonstrated by a new immunohistochemical marker mucin‐like glycoprotein associated with photoreceptor cells (MLGAPC) Aims: For further understanding of specific differentiation in retinoblastoma, we studied the expression of newly detected mucin‐like glycoprotein associated with photoreceptor cells (MLGAPC), which is specific for photoreceptor cells of retina and analogous to interphotoreceptor matrix proteoglycan‐1 (IMPG1). Methods and results: Surgically enucleated retinoblastomas (n=21; undifferentiated type, n=15, differentiated type, n=6) were immunohistochemically studied with a polyclonal antibody against MLGAPC, and 17/21 cases (81%) showed positive staining of tumour cells. We classified various staining patterns and structures into four groups: type 1 showing a granular intracellular scattered staining pattern with round small cells; type 2 showing a reticular staining pattern between spindle‐shaped tumour cells; type 3 showing radiating staining from the centre of Homer–Wright rosettes; type 4 showing ring‐shaped, radiating and granular staining associated with Flexner–Wintersteiner rosettes. Eleven of 15 undifferentiated retinoblastomas (73%) showed type 1 or 2, and all the six differentiated cases showed type 3 or 4. Image analysis of immunostaining revealed an increase in MLGAPC‐positive area from 0.48% in undifferentiated cases to 1.60% in differentiated cases, and a negative correlation was shown between mitotic frequency and MLGAPC‐positive area. Conclusions: This study proved MLGAPC as a valuable marker of retinoblastoma, and that photoreceptor differentiation takes place even in `undifferentiated' retinoblastoma.
Expression of human mucin genes in normal kidney and renal cell carcinoma
Authors: Leroy X , Copin M‐C , Devisme L , Buisine M‐P , Aubert J‐P , Gosselin B , Porchet N 
Published: March 2003

Expression of human mucin genes in normal kidney and renal cell carcinoma Aims: Human mucins are large O‐glycoproteins expressed by epithelial cells. Mucins are thought to be implicated in cell protection, cell adhesion and signalling. The aim of this study was to investigate the expression of the human mucin genes (MUC1–4, 5AC, 5B, 6–7) in normal kidney and renal cell carcinoma. Methods and results: We analysed by in‐situ hybridization, immunohistochemistry and reverse transcriptase‐polymerase chain reaction (RT‐PCR) the expression of these genes in normal adult kidney (n=14) and renal cell carcinomas (n=29). MUC1, MUC3 and MUC6 were expressed both in normal kidney and in renal carcinomas. In normal kidney, MUC1 was expressed in the distal convoluted tubules and in collecting ducts, whereas MUC3 was restricted to the proximal tubules. MUC4 was strongly expressed in epithelial urothelial cells of pyelocalyceal cavities. MUC6 was only detected by RT‐PCR. In renal carcinoma, we showed a heterogeneous expression of MUC1 and MUC3 with an over‐expression of MUC3 in renal clear cell carcinoma. The level of MUC3 expression by in‐situ hybridization was associated with the nuclear grade in clear cell carcinoma. Conclusions: This study is the first large series investigating human mucin gene expression in the kidney. MUC1, MUC3 and MUC6 are expressed in normal and tumour kidney. The over‐expression of MUC3 in renal cell carcinomas favours its implication in renal tumorigenesis.
Wide spectrum screening keratin as a marker of metaplastic spindle cell carcinoma of the breast: an immunohistochemical study of 24 patients
Authors: Adem C , Reynolds C , Adlakha H , Roche P C , Nascimento A G 
Published: March 2003

Wide spectrum screening keratin as a marker of metaplastic spindle cell carcinoma of the breast: an immunohistochemical study of 24 patients Aims: Metaplastic spindle cell carcinomas may be difficult to distinguish histologically from other spindle cell lesions in the breast. Variable staining with cytokeratin immunomarkers has been reported for metaplastic carcinomas. We evaluated the diagnostic utility of anti‐cytokeratin polyclonal antibody, wide spectrum screening keratin, to assess spindle cell breast lesions. Methods and results: Twenty‐four patients with spindle cell breast carcinoma and 31 patients with benign or malignant spindle cell tumours were studied using a panel of antibodies directed against multiple cytokeratins (AE1/AE3, CAM5.2, wide spectrum screening keratin), epithelial membrane antigen (EMA), and vimentin. Sites of origin for the 31 controls included breast, bone, and soft tissue. All but one (95.8%) metaplastic carcinomas stained positively with wide spectrum screening keratin. Only rare or focal immunoreactivity was observed with AE1/AE3 in four cases; however, sensitivity of AE1/AE3 was improved in 13 cases using steam EDTA as an antigen retrieval technique. Three cases were immunoreactive with CAM5.2 and eight cases were immunoreactive with EMA. All control cases lacked immunoreactivity with the cytokeratin panel and EMA. The spindle cells in the metaplastic breast tumours (88%) and in the controls (97%) stained with vimentin. Conclusions: Wide spectrum screening keratin may be the most useful and convenient antibody in differentiating metaplastic spindle cell carcinoma from other spindle cell lesions in the breast.
Extra‐abdominal desmoid fibromatosis: two familial cases with synchronous and metachronous multicentric hyalinizing nodules
Authors: Watanabe K , Ogura G , Tajino T , Suzuki T 
Published: March 2003

Extra‐abdominal desmoid fibromatosis: two familial cases with synchronous and metachronous multicentric hyalinizing nodulesAims:  Extra‐abdominal desmoid fibromatosis is an uncommon tumour. We present here two exceptional familial cases of extra‐abdominal desmoid fibromatosis, one of which was synchronous and metachronous.Methods and results:  The first patient was a 37‐year‐old woman who had noted a tumour growing on the dorsum of her right foot when she was 12 years old. She underwent excision of the tumour but in the following year the tumour recurred locally and grew into multiple nodules. Subsequently, multicentric tumours appeared in her knee, distal and posterior aspects of her thigh, right back and right anterior shoulder. Polyostotic fibrous dysplasia of the femur and cranium was found on radiological examination. The second patient was a 74‐year‐old man, the uncle of the first patient. He underwent an excisional operation of a tumour on the internal malleolus surface of his fibula when he was 46 years old. The tumour recurred 7 years later and was excised. His post‐operative course has been uneventful. The histology of the primary and recurrent tumours was distinctive and consistently showed hyalinizing scar‐like features.Conclusions:  Familial cases of extra‐abdominal desmoid fibromatosis with extensive multicentric lesions and distinctive hyalinizing scar‐like features are described. Recently, attenuated familial adenomatous polyposis with familial desmoid fibromatosis has been recognized, and familial desmoid fibromatosis without adenomatous polyposis may also be one of its variants. Although the present cases have no history of colon polyposis or carcinoma, monitoring of the intestinal tract would seem to be indicated.
Replenishment of RANTES mRNA expression in activated eosinophils fromatopic asthmatics
Authors: Velazquez J. R. , Lacy P. , Moqbel R. 
Published: March 2003

SummaryEosinophils have been shown to express the gene encoding regulated upon activation, normal T‐cell expressed and secreted (RANTES), a potent eosinophilotactic chemokine. RANTES protein expression in eosinophils has previously been shown to be up‐regulated by a number of agonists, including complement‐dependent factors (C3b/iC3b) and interferon‐γ (IFN‐γ). We hypothesized that gene expression of RANTES is regulated in these cells by eosinophil‐specific agonists. We analysed RANTES mRNA expression by reverse‐transcription polymerase chain reaction (RT‐PCR) in human peripheral blood eosinophils obtained from mild atopic asthmatics following stimulation over time. In resting eosinophils, a low level of RANTES mRNA was found to be constitutively expressed in all the atopic donors tested in this study (n = 6). Following stimulation with C3b/iC3b (serum‐coated surfaces), eosinophils released measurable levels of RANTES, while sustained transcript expression was detected for up to 24 hr of stimulation. In contrast, IFN‐γ (5 ng/ml) transiently and significantly (P < 0·05, n = 3) depleted relative amounts of RANTES PCR product (compared with β2‐microglobulin) after 1–4 hr of stimulation. RANTES transcript was again detectable after 24 hr of IFN‐γ incubation, suggesting that the pool of RANTES mRNA had been replenished. Other eosinophil‐active cytokines, interleukin‐3 (IL‐3), IL‐4, IL‐5 and granulocyte–macrophage colony‐stimulating factor, did not appear to modulate RANTES mRNA expression after 1 hr of incubation. The effect of IFN‐γ on RANTES mRNA was reversed by cycloheximide, suggesting that IFN‐γ may act by increasing the rate of translation of RANTES mRNA. These findings indicate that IFN‐γ may induce a rapid and transient effect on the translation and replenishment of RANTES mRNA in eosinophils. This novel observation supports the notion that eosinophils have the potential to replenish their stored and released bioactive proteins.
Interactions between hormone‐mediated and vaccine‐mediated immunotherapy for pulmonary tuberculosis in BALB/c mice
Authors: Hernandez‐Pando R. , Pavon L. , Orozco E. H. , Rangel J. , Rook G. A. W. 
Published: March 2003

SummaryProblems of logistics, compliance and drug resistance point to an urgent need for immunotherapeutic strategies capable of shortening the current 6‐month chemotherapy regimens used to treat tuberculosis, or of supplementing ineffective therapy. In this study we sought to define the mechanism of action of two immunotherapies, both of which have previously been shown to prolong survival. Secondly, we wished to identify any clinically useful synergy between these therapies. In BALB/c mice infected via the trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of partial resistance dominated by type 1 cytokines plus tumour necrosis factor‐α (TNF‐α) and interleukin‐1 (IL‐1), followed by a phase of progressive disease. This progressive phase is accompanied by increasing expression of IL‐4, and diminished expression of IL‐1 and TNF‐α. Animals in this late progressive phase of the disease (day 60) were treated with two injections (day 60 and day 90) of 0·1 or 1·0 mg of heat‐killed Mycobacterium vaccae, or with 3β,17β‐androstenediol (AED; 25 µg subcutaneously three times/week), or with both therapies. We show here using four techniques in parallel (morphometry, immunohistochemistry with automated cell counting, semiquantitative reverse transcription–polymerase chain reaction and enzyme‐linked immunosorbent assays of cytokines in lung extracts) that treatment with M. vaccae causes a switch back towards a type 1 cytokine profile, restoration of expression of IL‐1α and TNF‐α, and a switch from pneumonia to granuloma. This is very similar to the changes previously seen after treatment with AED. However, there was no evidence for synergy between M. vaccae and AED.
Poly‐guanosine motifs costimulate antigen‐reactive CD8 T cells while bacterial CpG‐DNA affect T‐cell activation via antigen‐presenting cell‐derived cytokines
Authors: Lipford G. B. , Bendigs S. , Heeg K. , Wagner H. 
Published: March 2003

SummaryPathogen‐derived pattern recognition ligands like lipopolysaccharide (LPS) and bacterial cytidine–guanosine (CpG)‐DNA not only activate dendritic cells and macrophages but are also mitogenic for B cells. Less clear are the claimed effects of CpG‐DNA on T cells, which range from direct activation, costimulation, or indirect transient activation via antigen‐presenting cell (APC)‐derived interferon type I (IFN type I). Here we demonstrate that CpG‐DNA sequence specifically triggers macrophages to produce IFN type I, interleukin (IL)‐12, IL‐6 and tumour necrosis factor (TNF), but lacks the ability to directly costimulate T cells. Strikingly, poly‐guanosine (poly‐G) extensions to CpG‐containing oligonucleotides (ODN) abolished the macrophage stimulatory potential yet generated T‐cell costimulatory activities. In fact, independently of CpG‐motifs, poly‐G‐ODN displayed the ability to costimulate T cells. Costimulation was operative on CD8 T cells but not CD4 T cells. Poly‐G‐mediated costimulation resulted in IL‐2‐driven T‐cell proliferation and induced cytolytic T cells. Overall the data imply that poly‐G motifs costimulate antigen reactive CD8 T cells, while CpG‐DNA motifs fail to do so but may affect T‐cell activation via APC derived cytokines such as IFN type I.
Structure/function studies of human decay‐accelerating factor
Authors: Brodbeck W. G. , Kuttner‐Kondo L. , Mold C. , Medof M. E. 
Published: March 2003

SummaryThe decay‐accelerating factor (DAF) contains four complement control protein repeats (CCPs) with a single N‐linked glycan positioned between CCPs 1 and 2. In previous studies we found that the classical pathway regulatory activity of DAF resides in CCPs 2 and 3 while its alternative pathway regulatory activity resides in CCPs 2, 3 and 4. Molecular modelling of the protein predicted that a positively charged surface area on CCPs 2 and 3 (including KKK125–127) and nearby exposed hydrophobic residues (L147F148) on CCP3 may function as ligand‐binding sites. To assess the roles of the N‐linked glycan and the above two sets of amino acids in the function of DAF, we mutated N61 to Q, KKK125–127 to TTT and L147F148 to SS. Following expression of the mutated cDNAs in Chinese hamster ovary cells, the glycosylphosphatidylinositol (GPI)‐anchored mutant proteins were affinity purified and their functions were assessed. In initial assays, the proteins were incorporated into sheep and rabbit erythrocytes and the effects of the mutations on regulation of classical and alternative C3 convertase activity were quantified by measuring C3b deposition. Since DAF also functions on C5 convertases, comparative haemolytic assays of cells bearing each mutant protein were performed. Finally, to establish if spatial orientation between DAF and the convertases on the cell surface played any role in the observed effects, fluid‐phase C3a generation assays were performed. All three assays gave equivalent results and showed that the N‐linked glycan of DAF is not involved in its regulatory function; that L147F148 in a hydrophobic area of CCP3 is essential in both classical and alternative pathway C3 convertase regulation; and that KKK125–127 in the positively charged pocket between CCPs 2 and 3 is necessary for the regulatory activity of DAF on the alternative pathway C3 convertase but plays a lesser role in its activity on the classical pathway enzyme.
Interleukin‐8 fails to induce human immunodeficiency virus‐1 expression in chronically infected promonocytic U1 cells but differentially modulates induction by proinflammatory cytokines
Authors: Tiemessen C. T. , Kilroe B. , Martin D. J. 
Published: March 2003

SummaryThis study addresses the role of interleukin (IL)‐8, a CXC‐chemokine, the level of which is reported to be raised in the peripheral circulation of human immunodeficiency virus‐1 (HIV‐1)‐infected individuals, during the induction of HIV‐1 expression from latency and during cytokine‐mediated HIV‐1 up‐regulation. IL‐8 at the higher concentrations tested (≥ 100 ng/ml) was unable to induce HIV‐1 expression in the chronically infected promonocytic U1 cell line, as measured by p24 antigen enzyme‐linked immunosorbent assay (ELISA), whereas at lower concentrations of 1 and 10 ng/ml, constitutive HIV‐1 expression was only marginally reduced. HIV‐1 replication in acutely infected U937 cells was also significantly reduced by IL‐8. The potent up‐regulation of HIV‐1 expression in U1 cells by tumour necrosis factor‐α (TNF‐α) remained unaffected by the addition of IL‐8. HIV‐1 induction by IL‐1β, IL‐6 and TNF‐β, cytokines grouped here as intermediate HIV‐1 inducers, was suppressed by IL‐8 at concentrations of 1 and 10 ng/ml. However, IL‐8 at 100 ng/ml did not significantly alter the effect of IL‐1β, synergized with IL‐6 in enhancing, and marginally suppressed TNF‐β‐induced HIV‐1 expression. IL‐8 suppressed granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and enhanced interferon‐γ (IFN‐γ)‐induced HIV‐1 expression in a dose‐dependent manner. Pretreatment of U1 cells with IL‐8 did not alter the IL‐8‐mediated effects on cytokine‐induced HIV‐1 expression, suggesting that this chemokine exerts its effect at the time of HIV‐1 induction or at a postinduction stage. Furthermore, IL‐8 was itself induced by cytokines that up‐regulate HIV‐1 expression in U1 cells and the levels produced correlated directly with the levels of p24 antigen produced, suggesting common pathways for cytokine induction of both HIV‐1 and IL‐8. These results show that IL‐8, typically a non‐inducer, can differentially modulate HIV‐1 expression in U1 cells and that this is dependent on the inducing cytokine and on the concentration of IL‐8.