bluuebunny/crossref_metadata_2025_split huggingface dataset:
Familial multiple gastrointestinal stromal tumours with associated abnormalities of the myenteric plexus layer and skeinoid fibres
Authors: Handra‐Luca A , Fléjou J‐F , Molas G , Sauvanet A , Belghiti J , Degott C , Terris B 
Published: March 2003

Familial multiple gastrointestinal stromal tumours with associated abnormalities of the myenteric plexus layer and skeinoid fibres Aims: Multiple familial gastrointestinal stromal tumours are rare. We report the third family with two cases of multiple gastrointestinal stromal tumours showing skeinoid fibres. Associated abnormalities of the myenteric plexus layer are described and new hypotheses for the histogenesis of gastrointestinal stromal tumours are formulated. Methods and results: Multiple gastrointestinal stromal tumours developed in the duodenum and proximal jejunum were removed from mother and son. No history of a specific syndrome or of mastocytosis was known. Light microscopy revealed typical gastrointestinal stromal tumours with skeinoid fibres. An unusual abnormality of the myenteric plexus layer, showing a diffuse spindle cell hyperplasia, was noted in the macroscopically normal digestive wall. No abnormalities of the ganglion cells were associated. Tumours and the spindle cell hyperplasia showed similar morphological and immunohistochemical features with expression of CD34 and CD117 antigens. Follow‐up revealed recurrences in the mother. Conclusion: The morphological characteristics of these two cases of familial gastrointestinal stromal tumours and of the associated abnormalities of the myenteric plexus layer, help to better explain the histogenesis of multiple familial gastrointestinal stromal tumours. The hyperplasia of the myenteric plexus could be considered a risk factor for recurrent tumours.
DNA topoisomerase IIα expression correlates with cell proliferation but not with recurrence in intracranial meningiomas
Authors: Konstantinidou A E , Patsouris E , Korkolopoulou P , Kavantzas N , Mahera H , Davaris P 
Published: March 2003

DNA topoisomerase IIα expression correlates with cell proliferation but not with recurrence in intracranial meningiomas Aims: To assess the value of topoisomerase IIα (TopoIIα) as a novel proliferation‐associated molecule, by correlating its immunohistochemical expression with Ki67 (MIB‐1), cell proliferating cell nuclear antigen (PCNA) and mitotic index in meningiomas. Furthermore, to investigate its relation to standard clinicopathological parameters and patients’ outcome. Methods and results: This retrospective study comprised a consecutive series of 57 patients with primary intracranial benign and atypical meningiomas. Six tumours recurred (10.5%) following complete surgical resection, within a follow‐up period ranging from 21 to 108 months (median 60 months). Archival formalin‐fixed paraffin‐embedded sections were stained with standard immunohistochemical methods. The lower proliferation indices were obtained with TopoIIα and the higher ones with PCNA. TopoIIα labelling index (LI) ranged from 0.1% to 10% (median 0.5%) and, along with Ki67 and PCNA LI, increased with malignancy grade (P=0.049, P=0.045 and P < 0.001, respectively), displaying though a significant overlapping between grades. A significant positive correlation was shown between TopoIIα and Ki67 (P < 0.001) or PCNA (P=0.032). In univariate and multivariate survival analysis, TopoIIα failed to predict meningioma recurrence and did not affect disease‐free survival. Only tumour size and Ki67 LI provided significant prognostic information in this regard. Conclusions: TopoIIα expression may be useful as a novel proliferation marker in meningiomas, presenting several advantages over the markers currently in use, notably providing a better estimate of the number of cycling cells and a more uniform nuclear staining pattern. However, it fails to discriminate between benign and atypical neoplasms and does not provide prognostic information beyond that obtained by Ki67.
Lobular endocervical glandular hyperplasia is a metaplastic process with a pyloric gland phenotype
Authors: Mikami Y , Hata S , Melamed J , Fujiwara K , Manabe T 
Published: March 2003

Lobular endocervical glandular hyperplasia is a metaplastic process with a pyloric gland phenotype Aims: Lobular endocervical glandular hyperplasia of the uterine cervix is a rare pseudoneoplastic lesion of the uterine cervix, described recently. Our aim was to characterize the clinicopathological and immunohistochemical features of lobular endocervical glandular hyperplasia, to elucidate its pyloric gland phenotype, and to distinguish it from adenoma malignum of the uterine cervix. Methods and results: Nine cases of lobular endocervical glandular hyperplasia were studied histologically and immunohistochemically. The average age of the nine patients was 48.8 years (range 38–64 years). Six cases were found incidentally, whereas in three cases a watery vaginal discharge and imaging studies suggested adenoma malignum preoperatively. Microscopically, lobular endocervical glandular hyperplasia ranged from 1 mm to 20 mm (mean 6.8 mm) in the largest horizontal extent and 1 mm to 10 mm (mean 3.9 mm) in depth, and was characterized by lobular arrangements of small glands composed of low columnar cells with pale eosinophilic cytoplasm and bland nuclei. Three cases showed a pseudo‐invasive growth. Intracytoplasmic mucin was predominantly PAS‐positive, and seven cases showed immunoreactivity for M‐GGMC‐1, an antibody that reacts with pyloric gland‐type mucin. Only focal and faint reactivity for CEA was seen, and ER was negative in all cases. The cytokeratin profile was CK7+/20– in all cases, in keeping with their Müllerian derivation. All three lesions examined contained chromogranin‐positive endocrine cells. After surgery all patients are well without recurrent disease (mean follow‐up was 48.4 months). Conclusions: Lobular endocervical glandular hyperplasia is a morphologically distinct pseudoneoplastic glandular lesion, which has unique phenotypic characteristics shared by pyloric glands of the stomach. Although most are found incidentally, some cases may show clinical and radiological features resembling those of adenoma malignum.
Malignant mesenchymoma of the uterus, arising in a leiomyoma
Authors: Bakker M A den , Hegt V Noordhoek , Sleddens H B F M , Nuijten A S M , Dinjens W N M 
Published: March 2003

Malignant mesenchymoma of the uterus, arising in a leiomyoma Aims: To document and find evidence for the rare occurrence of malignant progression of a benign uterine leiomyoma with divergent mesenchymal differentiation. In a 54‐year‐old female a large pedunculated tumour was encountered which had suddenly increased in size and had apparently arisen at the site of a subserosal uterine leiomyoma first described 19 years earlier. The tumour seemed histologically diverse in its composition. The possibility of malignant progression of the benign leiomyoma with divergent mesenchymal differentiation was entertained. Methods and results: In the resected tumour, smooth muscle, osseous and adipose components were identified and these were assessed using recognized histological criteria of malignancy. In addition to a benign smooth muscle component, malignant leiomyosarcomatous tissue was seen in addition to a malignant osseous component and a malignant adipose component. The tumour thus met the criteria of a malignant mesenchymoma. The relationship of the different components of the tumour was analysed by immunohistochemistry and with molecular loss of heterozygosity (LOH) analysis. In the osseous and leiomyosarcomatous components a similar LOH pattern was observed. The adipose component showed a distinct LOH pattern. Retention of smooth muscle differentiation in the osseous component was demonstrated by desmin immunostaining. Conclusion: Malignant transformation of benign uterine leiomyoma may rarely occur. Mesenchymal stem cells underlying these tumours may show divergent mesenchymal differentiation.
The TSC‐2 product tuberin is expressed in lymphangioleiomyomatosis and angiomyolipoma
Authors: Johnson S R , Clelland C A , Ronan J , Tattersfield A E , Knox A J 
Published: March 2003

The TSC‐2 product tuberin is expressed in lymphangioleiomyomatosis and angiomyolipoma Aims: Lymphangioleiomyomatosis is categorized by proliferation of abnormal smooth muscle cells (LAM cells) in the lungs and lymphatics and the presence of angiomyolipomas. Recently mutations in the tuberous sclerosis complex‐2 gene (TSC‐2) have been described in LAM cells and angiomyolipomas. The TSC‐2 protein tuberin is a tumour suppressor and its loss may result in cellular proliferation. We used immunohistochemistry to test the hypothesis that uncontrolled cellular proliferation in lymphangioleiomyomatosis is the result of reduced tuberin protein expression. Methods and results: Tissue from normal lung, normal kidney, lymphangioleiomyomatosis and angiomyolipomas was immunostained with three separate anti‐tuberin antibodies. Tuberin staining in normal tissues was similar to that previously described. Surprisingly, tuberin was strongly expressed in the LAM cells of all cases of lymphangioleiomyomatosis and angiomyolipoma at a greater level than in normal smooth muscle cells. The perivascular cells of angiomyolipomas, however, did not stain for tuberin. Conclusions: Our results suggest that a loss of tuberin protein in LAM cells is not the cause of the cellular proliferation seen in lymphangioleiomyomatosis. Lymphangioleiomyomatosis may result either from the expression of a mutant tuberin with abnormal function, as a result of mutations in functionally related proteins, or from more than one mechanism.
Lymph nodes in gastric B‐cell lymphoma: pattern of involvement and early histological changes
Authors: Ko Y H , Han J J , Noh J H , Ree H J 
Published: March 2003

Lymph nodes in gastric B‐cell lymphoma: pattern of involvement and early histological changes Aims: This study aims to analyse the histological pattern of nodal involvement in gastric B‐cell lymphoma and to detect early involvement of the lymph nodes. Methods and results: Histological findings of 37 resected primary gastric lymphomas with 1313 regional lymph nodes were analysed. The primary tumour was classified into four groups: MALT lymphoma, MALT lymphoma with a minor large B‐cell lymphoma (<20%), large B‐cell lymphoma with MALT lymphoma, and large B‐cell lymphoma without MALT lymphoma. Histological patterns of nodal involvement were divided into sinusoidal, subsinusoidal/marginal, follicular, and diffuse patterns. Semi‐nested polymerase chain reaction (PCR) analysis for IgH gene rearrangement was performed. Nodal involvement was found in 2/13 (15%) MALT lymphomas, 5/6 (83%) MALT lymphomas with a minor large B‐cell lymphoma, 9/12 (75%) large B‐cell lymphomas with MALT lymphoma, and 6/6 (100%) large B‐cell lymphomas without MALT lymphoma. The MALT lymphoma and MALT lymphoma with a minor large B‐cell lymphoma showed a predominantly sinusoidal and subsinusoidal pattern, whereas diffuse pattern predominated in large B‐cell lymphomas without MALT lymphoma and large B‐cell lymphomas with MALT lymphoma. The follicular pattern was least common, being observed in 10.2% of large B‐cell lymphomas without MALT lymphoma and large B‐cell lymphomas with MALT lymphoma. Sinusoidal obliteration with permeation of small monocytoid cells into subsinusoidal zone is a characteristic finding suggesting early nodal involvement of MALT lymphoma. Conclusions: Histological patterns of nodal involvement in gastric B‐cell lymphoma vary according to the histological grade. Immunostaining for CD20 with or without PCR analysis for IgH gene rearrangement would be a useful ancillary method to confirm lymphomatous involvement.
Expression of intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 in human crescentic glomerulonephritis
Authors: Moon K C , Park S Y , Kim H W , Hong H K , Lee H S 
Published: March 2003

Expression of intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 in human crescentic glomerulonephritisAims:  In glomerulonephritis, intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) may play important roles in the formation of crescents. These studies are designed to evaluate the expression patterns of ICAM‐1 and VCAM‐1 in human crescentic glomerulonephritis and to determine the cellular origin of adhesion molecules in the crescentic lesions.Methods and results:  We examined the expression of ICAM‐1 and VCAM‐1 proteins in renal biopsies with cellular (n=7), fibrocellular (n=9) or fibrous (n=4) crescentic glomerulonephritis, and six controls by immunohistochemistry. mRNA expression of ICAM‐1 and VCAM‐1 was further evaluated by RNA in‐situ hybridization. Cytokeratin or CD68 immunohistochemistry was performed on the same sections, where in‐situ hybridization had been carried out. In cellular crescents, ICAM‐1 and VCAM‐1 proteins were over‐expressed to a similar extent. Of the three types of crescents, the extent of ICAM‐1 immunopositivity was the greatest in the cellular crescents and decreased towards the fibrous crescents (P < 0.05). Yet the extent of VCAM‐1 immunoreactivity was not different between the types. Fibrous crescents still contained some epithelial cells and showed only VCAM‐1 expression. In the glomeruli with cellular or fibrocellular crescents, the extent of ICAM‐1 immunopositivity in the glomerular tufts was significantly larger than that of VCAM‐1 (P < 0.05). In an in‐situ hybridization study, the mRNA expression patterns of ICAM‐1 and VCAM‐1 paralleled their protein expressions. A double‐labelling study showed that the signal for ICAM‐1 and VCAM‐1 mRNAs was mainly present in cytokeratin‐positive and CD68‐negative cells in the crescentic lesions.Conclusions:  These results suggest that glomerular parietal epithelial cells in cellular crescents up‐regulate both ICAM‐1 and VCAM‐1, and that some epithelial cells retained in fibrous crescents persistently over‐express VCAM‐1, but not ICAM‐1. They also suggest that ICAM‐1 is involved in early leucocyte recruitment into glomeruli in crescentic glomerulonephritis.
Follicular baso‐squamous melanocytic tumour of the skin
Authors: Riccioni L , Cenacchi G , Ragazzini T , Collina G 
Published: March 2003

Aims: We describe a previously unrecognized pigmented tumour of the skin and suggest a possible relationship with the follicular bulb.Methods and results: A pigmented epithelial neoplasm clinically simulating a malignant melanoma of the skin was present in a 92‐year‐old woman, on her left leg. It was composed of three cell types: squamous cells with trichilemmal keratinization, basaloid cells and dendritic melanocytes. The presence of three cell types was confirmed by immunohistochemistry and electron microscopy.Conclusions: The tumour showed differentiation towards the hair follicular bulb and the descriptive term of follicular baso‐squamous melanocytic tumour is suggested.
Up‐modulation of interferon‐γ mediates the enhancement of spontanous cytotoxicity in prolactin‐activated natural killer cells
Authors: Matera L. , Contarini M. , Bellone G. , Forno B. , Biglino A. 
Published: March 2003

SummaryProlactin (PRL) has been shown to participate in lymphocyte activation. In particular, the constitutive natural killer (NK) and the lymphokine‐activated killer (LAK) cytotoxicity of CD56+ CD16+ cells is increased by its physiological to supraphysiological concentrations. As PRL has been shown to up‐regulate the production of interferon‐γ (IFN‐γ) by peripheral blood mononuclear cells, we studied its effect on IFN‐γ production by NK cells as a possible mechanism of autocrine activation of cytotoxicity. Released and intracellular IFN‐γ, as well as IFN‐γ mRNA expression, were increased by pituitary and recombinant human PRL, which stimulated optimal NK and LAK cytotoxicity. Treatment with blocking anti‐IFN‐γ monoclonal antibody (mAb) selectively affected PRL‐increased killing of K562 targets, demonstrating that PRL‐mediated enhancement of spontaneous cytotoxicity depends, at least in part, on up‐regulation of IFN‐γ.
Regulation of epidermal Langerhans cell migration by lactoferrin
Authors: Cumberbatch M. , Dearman R. J. , Uribe‐luna S. , Headon D. R. , Ward P. P. , Conneely O. M. , Kimber I. 
Published: March 2003

SummaryLactoferrin (LF) is a member of the transferrin family of iron‐binding glycoproteins to which several anti‐inflammatory functions have been ascribed. LF has been shown to down‐regulate expression of the pro‐inflammatory cytokine tumour necrosis factor‐α (TNF‐α), although the possibility has been raised that the activity of LF in this regard was indirect and secondary to its ability to bind to and inactivate the bacterial lipopolysaccharide (LPS) used to induce cytokine production. However, the identification of putative membrane receptors for LF raises the possibility that the interaction of LF with its receptor may be one important route through which this protein exerts anti‐inflammatory activity. In the present investigations the biological properties of LF have been examined in a model of cutaneous immune function where the allergen‐induced migration of epidermal Langerhans cells (LC) from the skin and their subsequent accumulation as dendritic cells (DC) in skin‐draining lymph nodes are known to be dependent upon the de novo synthesis of TNF‐α, but independent of exogenous LPS. Consistent with the protein having direct anti‐inflammatory properties, it was found that the intradermal injection of recombinant murine LF (either iron‐saturated or iron‐depleted LF) inhibited significantly allergen (oxazolone) ‐induced LC migration and DC accumulation. That these inhibitory effects were secondary to the inhibition of local TNF‐α synthesis was suggested by the findings that first, LF was unable to inhibit LC migration induced by intradermal injection of TNF‐α itself, and second, that migration stimulated by local administration of another epidermal cytokine, interleukin 1β, which is also dependent upon TNF‐α production, was impaired significantly by prior treatment with LF. Finally, immunohistochemical analyses demonstrated the presence of LF in skin, associated primarily with keratinocytes. Collectively these data support the possession by LF of direct immunomodulatory and/or anti‐inflammatory activity, probably associated in this case with inhibition of cytokine production. Furthermore, the results suggest that as a constituent of normal skin, LF may play a role in homeostatic regulation of cutaneous immune function.
Lack of metallothionein‐I and ‐II exacerbates the immunosuppressive effect of ultraviolet B radiation and cis‐urocanic acid in mice
Authors: Reeve V. E. , Nishimura N. , Bosnic M. , Michalska A. E. , Choo K. H. A. 
Published: March 2003

SummaryThe effect of a null mutation for the metallothionein (MT)‐I and ‐II isoforms in mice on the immunosuppressive action of ultraviolet B (UVB; 280–320 nm) radiation has been examined. Mice were exposed to a series of increasing daily UVB doses, each dose administered to the dorsum on 3 consecutive days. Erythema was assessed, and measured as its oedema component by the post‐irradiation dorsal skinfold thickness, but there was no effect of the null mutation (MT–/–) observed after 3 × 3·4 kJ/m2 of UVB radiation. Immune function was assessed by the contact hypersensitivity (CHS) response, which was initiated by sensitization on unirradiated abdominal skin, and thus demonstrated the systemic effects of dorsal treatments. In comparison with the wild‐type MT+/+ mouse, the MT–/– mouse was significantly more immunosuppressed by moderate daily UVB doses (1·75–5·9 kJ/m2). When topically applied cis‐urocanic acid (cis‐UCA) replaced UVB radiation as the immunosuppressive agent, contact hypersensitivity in MT–/– mice was again markedly more suppressed than in MT+/+ mice, in a dose‐responsive manner. The results infer that MT, which was shown immunohistochemically to be strongly induced in the epidermis of MT+/+ mice, but to be absent in MT–/– epidermis, has the potential to protect from photoimmunosuppression, and that the mechanism of action may be via the inactivation of the epidermal UVB‐photoproduct, cis‐UCA.
Repeat bacterial challenge in a subcutaneous chamber model results in augmented tumour necrosis factor‐α and interferon‐γ response, and suppression of interleukin‐10
Authors: Houri‐haddad Y. , Soskolne W. A. , Halabi A. , Barak V. , Shapira L. 
Published: March 2003

SummaryThe present study compared the effect of a single or a repeat challenge with the Gram‐negative pathogen Porphyromonas gingivalis on the local inflammatory response within subcutaneous chamber model in mice. Subcutaneous chambers were implanted 2 weeks prior to the final challenge. The repeat‐challenge (REP) group received two intrachamber bacterial injections 14 days apart, while the single‐injection group (SIN) received only a single bacterial challenge. Injection of saline was used as the control. The cellular contents of the chamber exudates were used for differential cell counts, and the supernatants were analysed for tumour necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), and interleukin (IL)‐10 levels. Immunoglobulin G1 (IgG1) and IgG2a levels to P. gingivalis in the exudates were also determined. The results showed that the leucocyte counts increased significantly post‐challenge, and the REP group showed the highest number of lymphocytes and neutrophils. Both P. gingivalis‐challenged groups exhibited significant increase in TNF‐α and IL‐10 levels at day 1 post‐challenge. TNF‐α levels in the chamber exudate were threefold higher in the REP group compared with the SIN group on day 1 post‐challenge (P < 0·05). In contrast, IL‐10 levels were significantly lower in the REP group 1 day post‐challenge compared with the SIN group. The REP group had significantly higher levels of IFN‐γ at baseline, and this difference remained significant 1 day post‐challenge. Analysis of antibody levels to P. gingivalis showed that while the control and the SIN groups had no anti‐P. gingivalis IgG in the chamber exudate during the 7‐day study period, the REP group showed high anti‐P. gingivalis IgG levels. In addition, the titres of IgG2a were fivefold higher than the IgG1 titres. The results showed that a repeat local challenge with P. gingivalis augmented the proinflammatory cytokines TNF‐α and IFN‐γ, while inhibiting the accumulation of the anti‐inflammatory cytokine IL‐10. This shift towards a T helper 1 (Th1)‐dominant response was reflected in the relatively high anti‐P. gingivalis IgG2a titres in the local inflammatory environment 7 days post‐challenge.
Nerve growth factor‐β induces mast‐cell marker expression during in vitro culture of human umbilical cord blood cells
Authors: Welker P. , Grabbe J. , Gibbs B. , Zuberbier T. , Henz B. M. 
Published: March 2003

SummaryNerve growth factor‐β (NGF) is known as a growth factor for human basophils and murine mast cells and has recently been shown to also up‐regulate mast cell characteristics in human leukaemic mast cells. We have examined here the effect of NGF on the differentiation of normal human mast cells from cord blood progenitors during culture with stem cell factor (SCF), NGF alone or in combination, or fibroblast supernatants. All these supplements induced mast cell immunoreactivity against tryptase, c‐Kit and FcεRIα, but none of the cells reacted against the basophil specific antibody 2D7 before or during culture. Intracellular tryptase activity increased as well, with maximal levels on combined culture with SCF and NGF. On reverse transcription–polymerase chain reaction (RT–PCR), cells lacked tryptase and chymase and expressed low levels of FcεRI and c‐Kit mRNA prior to culture, with marked up‐regulation of FcεRI and c‐Kit, and with de novo expression of mast‐cell specific α‐ and β‐tryptase by week 3, and of chymase by week 5. Only the TrkA and not the p75 NGF receptor was detected at m‐RNA and protein level, and only the TrkA NGF receptor was up‐regulated during NGF‐driven culture. These findings show therefore that, like SCF, NGF is another growth factor that can induce and regulate human mast‐cell development and differentiation.