bluuebunny/crossref_metadata_2025 huggingface dataset:
Stromelysin, gelatinase A and TIMP‐1 in prosthetic interface tissue: a role for macrophages in tissue remodelling
Authors: HEMBRY R.M. , BAGGA M.R. , REYNOLDS J.J. , HAMBLEN D.L.
Published: April 2007

Aseptic loosening of prosthetic components is the most important long‐term complication of total joint replacement. To investigate the underlying destructive mechanisms, periprosthetic tissues from both well‐fixed and loosened sites from six patients, undergoing surgery for aseptic loosening of knee or hip prostheses, were analysed in detail by immunohistochemical methods for the presence, of matrix metalloproteinases and tissue inhibitor of metalloproteinases‐1 (TIMP‐1). The tissues contained small numbers of cells positive for either collagenase, stromelysin, gelatinase A or TIMP‐1; these were randomly distributed, neither specifically next to the bone interface nor to wear particles, and the number of positive cells did not correlate with macroscopic observations at operation. Gelatinase A was co‐localized in cells with prolyl‐4‐hydroxylase, an enzyme involved in collagen synthesis. The predominant cell type in these tissues was shown to be the macrophage by the use of cell marker antibodies. Dual localization was not technically possible but the results strongly suggest that monocyte/macrophages were the primary source of gelatinase A and TIMP‐1. Stromelysin was immunolocalized on connective tissue matrix in four patients, and gelatinase A in one patient, and were also observed in tissues in which there was no evidence of cellular synthesis of these enzymes. This suggests that secretion had taken place previously, resulting in enzyme bound to matrix for some time. Taken together, these data indicate that localized focal connective tissue remodelling occurs in periprosthetic tissues from both well fixed and loosened sites.
Immunohistochemical detection of O‐acetylated sialomucins in intestinal metaplasia and carcinoma of the stomach
Authors: MULLEN P.J. , CARR N. , MILTON J.D. , RHODES J.M.
Published: April 2007

Eighty‐two selected gastric mucosal biopsy or resection specimens were stained both conventionally, to classify subtypes of intestinal metaplasia and carcinoma, and immunohistochemically with a mouse monoclonal antibody (MMM‐17), raised against normal human colonic mucin, which has an affinity for di‐ and/or tri‐O‐acetylated sialomucin. The aims of the study were to reassess the prevalence of O‐acetylated sialomucins in normal, metaplastic and carcinomatous gastric mucosa and to investigate whether the production of these mucins by intestinal metaplasia is related to its associated mucosal pathology. O‐acetylated sialomucins were not seen in normal mucosa. They were, however, prevalent in all sub‐types of metaplastic (64.8%) and carcinomatous (42.9%) mucosa. Type 1 intestinal metaplasia was significantly more likely to contain this type of mucin if Helicobacter pylori infection was identifiable in the adjacent gastric mucosa (81.0% v. 38.5%, P < 0.025). Type 3 showed a similar, albeit nonsignificant, relationship (100% v. 62.5%). O‐acetylated sialomucins are, therefore, much more prevalent in gastric intestinal metaplasia and carcinoma than previously recognized by conventional staining techniques. The production of this type of mucin by intestinal metaplasia may reflect an adaptive response to alterations in the luminal environment such as an increase in bacterial content.
Role of complement in renal tubular damage
Authors: KHAN T.N. , SINNIAH R.
Published: April 2007

Deposition of immunoglobulins, complement proteins C1q, C3c, C3d, C4, C5, C6, C7, C8, C9, and terminal complement complex neoantigens in the renal tubulointerstitium was studied in serial sections by immuno‐fluorescence microscopy. Renal tissue from 45 cases with various glomerular diseases, including 8 controls, was studied. The patients were divided into groups; one with tubulointerstitial lesions (24 cases) and the other without (13 cases). The immunoproteins were deposited mainly in the tubular basement membrane and blood vessels. Compared with controls there was a significantly increased staining score for C5 to C9 in the tubular basement membrane in both disease groups. However, the increase in terminal complement complex neoantigens score was significant only in the disease group with tubulo interstitial lesions. The changes in C3d score were not significant. Serial sections showed consistent and heavy ribbon‐like deposits of complement proteins C3d, C5 to C9, and terminal complement complex neoantigens in corresponding locations of the segments of tubular basement membrane, mainly in the disease group with tubulointerstitial lesions and especially in the damaged tubules. These findings suggest that in situ activation of the complement cascade leads to the deposition of terminal complement complex neoantigens. Complement activation in the basal area of the tubules may, therefore, be an important pathogenetic mechanism in tubulointerstitial damage.
Pathological prognostic factors in breast cancer. IV: Should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma
Authors: PEREIRA H. , PINDER S.E. , SIBBERING D.M. , GALEA M.H. , ELSTON C.W. , BLAMEY R.W. , ROBERTSON J.F.R. , ELLIS I.O.
Published: April 2007

In a study of 1529 patients with primary operable breast carcinoma we have assessed the effect of applying both histological grade and tumour type to determine their comparative value as prognostic factors in human breast cancer. The prognostic group the patient was placed in, based on histological type alone, was less accurate than using grade and type together for many tumours. The importance of performing histological grading of ductal/no special type carcinoma (50% of the women in this series) is confirmed in this series. The 10‐year‐survival varied from 76% for women with grade 1 carcinoma to 39% for those with grade 3 tumours. Some of the ‘special types’ of breast carcinoma including tubular, tubulo‐lobular, invasive cribriform and grade 1 mucinous carcinomas behaved as would be predicted, with a greater than 80% 10‐year‐survival in this series. Others, including grade 2 mucinous carcinomas, however, behaved less well with a 60% to 80% 10‐year‐survival. Indeed, many of the histological tumour types including tubular mixed, ductal/no special type, mixed ductal with special type and lobular carcinomas of classical, solid or mixed types showed a variation in behaviour that could not be predicted by typing alone. Histological grade and tumour type, when used together, more accurately predicted prognosis. In multivariate analysis of a larger group of 2658 cases of primary breast carcinomas (including the 1529 study cases) when histological grade, lymph node status and tumour size were entered, grade was the most important factor in predicting for survival. When histological type of carcinoma was included it was also found to be independently significant, although comparatively of less importance than grade. We conclude that tumours should be typed and graded in order to predict prognosis most accurately and to enable the choice of optimum treatment for women with primary breast carcinoma.
Smooth muscle tumours presenting as pleural neoplasms
Authors: MORAN C.A. , SUSTER S. , KOSS M.N.
Published: April 2007

Five smooth muscle tumours presenting as pleural neoplasms are presented. The patients were three women and two men aged between 21 and 69 years (mean = 45 years). Clinically, one patient presented with chest pain, one with empyema and the other three were asymptomatic. Two of the tumours were located in the left side of the chest cavity and three in the right side. In four cases, the lesions presented as solitary pleural‐based masses that varied in size from 10–18 cm in greatest dimension; in two of these cases, involvement of the diaphragm was present in addition to the pleural involvement. In one case, the tumour was seen to totally encase the right lung simulating the growth pattern of malignant mesothelioma. Histologically, three cases displayed an atypical spindle cell proliferation with marked cellular pleomorphism, mitoses and areas of hemorrhage and necrosis. The other two cases were characterized by a bland‐appearing smooth muscle proliferation of uncertain malignant potential composed of elongated cells with a moderate amount of eosinophilic cytoplasm and cigar‐shaped nuclei, lacking significant nuclear pleomorphism or mitotic activity. Immunohistochemical studies showed strong positivity for alpha‐smooth muscle actin in all cases, and for desmin in four of five cases, and a focal positive reaction for keratin in one case. Ultrastructural examination in one of the high‐grade tumours showed features of smooth muscle differentiation. Three of the patients were treated by complete surgical excision while, in the other two patients, the lesions were incompletely resected. Follow‐up ranging from 2–12 months has not shown evidence of recurrence in those patients with complete surgical resection, or metastasis in any of the patients. These cases appear to represent a previously undescribed form of primary pleural neoplasm. Because of the differences in biological behaviour compared with other types of pleural neoplasms, smooth muscle tumours should be included in the differential diagnosis of primary spindle cell tumours of the pleura.
Atypical polypoid adenomyomas of the uterus
Authors: FUKUNAGA M. , ENDO Y. , USHIGOME S. , ISHIKAWA E.
Published: April 2007

We performed a clinicopathological immunohistochemical, ultrastructural, and flow cytometric study on six cases of atypical polypoid adenomyoma of the uterus including one with an adenocarcinoma within it. The tumours occurred in nulliparous women aged 22–48 years (average, 33.0 years); three arose in the uterine corpus, and three in the endocervix. Histologically, they were composed of endometrial glands admixed with a stromal component of interlacing bundles of smooth muscle cells. The glands exhibited varying degrees of architectural and cytological atypia. Most of the stromal cells showed strong staining for HHF35, alpha‐smooth muscle actin, and vimentin, and some cells contained desmin. Electronmicroscopy, in one case, confirmed the presence of a well‐differentiated smooth muscle component. The stromal component may arise as a result of extensive metaplasia of endometrial stromal cells. Uninvolved endometrium showed ciliated cell metaplasia in three patients, and atypical complex hyperplasia in two. One patient had a well‐differentiated adenocarcinoma of endometrioid type arising in an endocervical atypical polypoid adenomyoma. All tumours had a diploid DNA content and relatively small S phase fraction (average, 6.23%). The follow‐up periods ranged from 4 to 42 months (average, 13.5 months), and all patients were alive and well. Although the histogenesis of atypical polypoid adenomyoma of the uterus remains uncertain, it is suggested that it may arise because of oestrogen‐related factors.
Keratin immunoreactivity in melanoma of soft parts (clear cell sarcoma)
Authors: MOOI W.J. , DEENIK W. , PETERSE J.L. , HOGENDOORN P.C.W.
Published: April 2007

Seven of 24 soft tissue melanomas were shown to express keratins using antibodies CAM 5.2, LP34 and MNF116. No clinical or histological differences were seen in these seven cases when compared with the 17 keratin negative cases.
Assessment of cell proliferation in normal and pathological bone marrow biopsies: a study using double sequential immunophenotyping on paraffin sections
Authors: PELLEGRINI W. , FACCHETTI F. , MAROCOLO D. , SALVI L. , CAPUCCI A. , TIRONI A. , ROSSI G.
Published: April 2007

The proliferative activity of the haematopoietic and plasma cells in bone marrow was evaluated under normal and neoplastic conditions, by means of a sequential double immunostaining technique, using monoclonal antibody MIB‐1 recognizing the cell proliferation‐associated nuclear antigen Ki‐67, and antibodies against glycophorin‐C, myeloperoxidase, factor VIII‐related antigen, and immunoglobulin light chains. Fifty‐eight B5 fixed, paraffin‐embedded bone marrow biopsies were analysed, including 11 normal controls, 10 cases of myelodysplasia, 14 cases of chronic myeloproliferative disorder, eight cases of acute non‐lymphoid leukaemia, and 15 cases of myeloma. In normal marrows, the highest proliferative activity was noticed in the erythroid cells (75% to 95%; mean 90%), in comparison with myeloid precursors (15% to 80%; mean 38%), and megakaryocytes (10% to 20%; mean 14%); no Ki‐67 positive plasma cells were found. In all investigated haematological disorders, the expression of MIB‐1 by erythroid cells was similar to that observed in controls. Similarly, the percentage of MIB‐1+ myeloid precursors in chronic myeloproliferative disorders and myelodysplasia largely overlapped the values observed in normals, and comparable values were also found in the blast cells from acute non‐lymphoid leukaemia type M1 and M2. These findings suggest that the evaluation of either erythroid or myeloid proliferative activity is of little value in the differential diagnosis between these myeloproliferative disorders. By contrast, the obvious increase of Ki‐67 expression of megakaryocytes in chronic myeloproliferative disorders, with labelling also of micro‐megakaryocytes, might sustain the diagnosis in controversial cases. Since cases of mature myeloma showed less than 2% of Ki‐67 positive cells, evaluation of proliferative activity is of no value in the differential diagnosis with reactive plasmacytosis. The sequential double immunophenotyping for Ki‐67 antigen and for haematopoietic cell lineage‐associated markers can be applied in a consistent manner to routine bone marrow biopsies to evaluate proliferating cells in normal and neoplastic conditions.
Strumal carcinoid of the ovary associated with hyperinsulinaemic hypoglycaemia and cutaneous melanosis
Authors: ASHTON M.A.
Published: April 2007

Using immunohistochemical techniques ovarian carcinoid tumours can be shown to contain a wide variety of neuro‐hormonal peptides but clinical effects, apart from the carcinoid syndrome, are very rare. Non‐islet cell tumours with documented hyperinsulinaemic hypoglycaemia are also rare. This is the first recorded case of an ovarian strumal carcinoid associated with hyperinsulinaemic hypoglycaemia. Concurrent skin hyperpigmentation is believed to have resulted from the effects of tumour derived α‐melanocyte stimulating hormone or an antigenically similar, biologically active peptide.
Association between the apoptotic index and established prognostic parameters in endometrial adenocarcinoma
Authors: HEATLEY M.K.
Published: April 2007

The aim of this study was to determine if the apoptotic index can be readily determined for endometrial carcinoma in hysterectomy specimens and to establish if any association exists between the apoptotic index and tumour grade and stage. The apoptotic index, defined as the percentage of morphologically identified apoptotic cells and apoptotic bodies in 3000 tumour cells, was calculated for 15 adenocarcinomas of the endometrium. An association between apoptotic index and tumour grade and stage was sought. Two grade 3 adenocarcinomas of endometrium had a higher apoptotic index (5.15% to 6.43%) than 13 grade 1 and 2 lesions (1.18% to 3.8%) and formed a distinct group in this series. No association between apoptotic index and tumour stage was demonstrable. Apoptotic index can be readily estimated in routine hysterectomy specimens for endometrial adenocarcinoma. A high apoptotic index shows an association with features normally correlated with a poor clinical outcome although its value as an independent prognostic index has yet to be established.
Choriocarcinoma in situ: a case at an early gestational stage
Authors: FUKUNAGA M. , USHIGOME S. , ISHIKAWA E.
Published: April 2007

A case of choriocarcinoma in situ arising in an 11 week gestational placenta is reported. Histologically, a localized nodule, measuring 5 mm, of neoplastic trophoblastic proliferation appeared to arise directly from normal stem villi and projected into the intervillous space. The tumour was composed of biphasic cytotrophoblast and syncytiotrophoblast. No fetal elements were observed. The patient had a normal full‐term spontaneous vaginal delivery 22 months after curettage and was free of disease without therapy at 32 months. This tumour provides evidence for an origin of choriocarcinoma from villous trophoblast. Our report illustrates the need to perform thorough microscopic examination of the products of conception, especially in the absence of a fetus or fetal parts.
Dual carcinoid/epithelial neoplasia of the appendix
Authors: CARR N.J. , REMOTTI H. , SOBIN L.H.
Published: April 2007

We report a series of 13 lesions of the human vermiform appendix in which a carcinoid component was associated with a separate non‐carcinoid epithelial component that included an adenoma‐like lesion of the mucosal epithelium. We use the term dual carcinoid/epithelial neoplasia to describe this phenomenon. The carcinoid component was insular/trabecular in nine cases, tubular in one case and of goblet cell type in three. The epithelial component was a mucinous cystadenoma in four, a mucinous tumour of uncertain malignant potential in three, and a mucinous cystadenocarcinoma in six. No intermediate cell population was seen and in three cases the carcinoid and epithelial components were in different parts of the appendix, leading us to suggest that these lesions may be true ‘collision’ tumours in which two neoplasms have arisen in the same organ. The prognosis appears to be no worse than for either of the components alone, but conclusions regarding these lesions must be guarded on account of their rarity and the small numbers available for study.
Mantle cell lymphoma: a clinicopathological study of 55 cases
Authors: PITTALUGA S. , WLODARSKA I. , STUL M.S. , THOMAS J. , VERHOEF G. , CASSIMAN J.J. , BERGHE H. VAN DEN , WOLF‐PEETERS C.DE
Published: April 2007

A recently described unifying proposal for mantle cell lymphoma has led to the formulation of strict diagnostic criteria based on morphology, immunology and molecular data to define this specific entity. Previous studies were often based on broader definitions such as centrocytic lymphoma, intermediately differentiated lymphoma or mantle zone lymphoma and, therefore, included a variety of entities with some, but not all, features ascribed to the mantle cell lymphoma. Since the publication of the unifying proposal no comprehensive studies have been published to confirm and support it. We selected 55 cases of mantle cell lymphoma collected in our institution in order to evaluate the validity of the proposal and, by using strict criteria, we analysed the morphological features, their variations and the changes occurring in the course of the disease as well as its clinical behaviour. The analysis of this material demonstrates that mantle cell lymphoma affects predominantly elderly males presenting with an advanced stage of disease. Twenty‐four out of 55 patients died with, or of, the disease with a median survival of 32 months, even though most of them received aggressive chemotherapy. In all cases the histological features were strikingly uniform and most cases had a diffuse growth pattern. The neoplastic cells corresponded to small cleaved cells with a minimal variation in shape and size from one case to the other. The phenotype of the neoplastic cells was remarkably constant with expression of several pan‐B cell markers, IgM, IgD and CD5, and lack of CD10 and CD23. Sixteen cases, which were followed by consecutive biopsies, showed only slight morphological changes during the course of the disease and only four cases showed histological progression. Forty cases were documented by cytogenetics, of which 15 showed t(11; 14)(q13;q32). We examined 28 cases for DNA rearrangement of the BCL‐1 locus; it was detected in 50% of the cases, with most breakpoints occurring at the major translocation cluster. This study demonstrates that when selection criteria are strictly applied, mantle cell lymphoma represents a disease entity with a uniform presentation, distinctive morphology, immunophenotype and a strong association with t(11;14)(q13;q32).
Primary cutaneous sarcomas showing rhabdomyoblastic differentiation
Authors: WONG T‐Y. , SUSTER S.
Published: April 2007

Rhabdomyosarcoma is a rare soft tissue neoplasm most commonly encountered in childhood and adolescence which has a predilection for the head and neck area, the genito‐urinary tract and the extremities. Primary cutaneous presentation is extremely unusual and has been rarely reported in the literature. Herein, we describe two cases of rhabdomyosarcoma arising in the dermis of a 9‐year‐old girl and an 86‐year‐old man. Clinically, the tumours presented as solitary plaque‐like or nodular lesions confined to the skin of the nose and chest wall, respectively. Histologically, the tumour in the first patient corresponded to an embryonal rhabdomyosarcoma. The tumour recurred locally four times, and in the last recurrence, showed features resembling those of malignant ‘triton’ tumour with fascicles of S‐100 protein‐positive spindle cells admixed with the rhabdomyoblastic components. The tumour in the second patient corresponded to the solid variant of alveolar rhabdomyosarcoma. Immunohisto‐chemical studies in both tumours showed positive labelling for muscle‐specific actin, desmin and vimentin. Ultrastructural examination in one case showed clusters of intermediate filaments in the cytoplasm recapitulating abortive sarcomeric structures consistent with rhabdomyoblastic differentiation. Both patients developed repeated recurrences over a period of 2–4 years despite adequate surgical excision, and the second patient had an axillary lymph node metastasis. Primary cutaneous rhabdomyosarcoma should be considered in the evaluation of small ‘blue cell’ tumours or undifferentiated malignant neoplasms of the skin, and appropriate immunohistochemical studies in conjuction with electron microscopy should be employed for proper evaluation of such lesions.
Association between mucosal hyperplasia of the appendix and adenocarcinoma of the colon
Authors: YOUNES M. , KATIKANENI P.R. , LECHAGO J.
Published: April 2007

Mucosal hyperplasia of the appendix is a seemingly benign change of poorly understood significance, at times found in patients with colorectal malignancy. To determine the incidence of this change and its association with colonic adenocarcinoma, we have examined the appendiceal mucosa in 122 ileocolectomy specimens gathered between 1987 and 1990, and in 273 consecutive appendectomies carried out during 1990 at The Methodist Hospital in Houston, Texas. We found that 23 out of 122 ileocolectomies (18.8%) showed mucosal hyerplasia of the appendix and, of these, 17 (77%) were associated with colorectal malignancy, predominantly of the right side. Moreover, 24 of 273 appendectomies (8.8%) exhibited the presence of mucosal hyperplasia and, of these, six (25%) also were associated with adenocarcinoma of the colon. On the basis of this significant rate of association, we feel that a concomitant colorectal carcinoma should be ruled out in patients who exhibit mucosal hyperplasia of the appendix.
Heterogeneity of bcl‐2 expression in MALT lymphoma
Authors: ASHTON‐KEY M. , BIDDOLPH S.C. , STEIN H. , GATTER K.C. , MASON D.Y.
Published: April 2007

Bcl‐2 protein expression was studied in a series of 58 MALT lymphomas using a monoclonal antibody which recognises this protein in routinely processed paraffin embedded tissue. Thirty‐three of 58 cases showed heterogeneity for bcl‐2 expression, 18 of 58 cases were bcl‐2 positive and 7 of 58 were bcl‐2 negative. High grade and low grade MALT lymphomas showed different patterns of staining. All 21 low grade tumours were positive for bcl‐2, though in seven cases only a proportion of the neoplastic cells expressed this protein. In the 37 high grade tumours the majority of the neoplastic cells were negative with seven cases showing no reactivity at all. These findings give further support to the theory that MALT lymphomas differ in pathogenesis to nodal lymphomas and suggest that the good prognosis of MALT lymphomas may partly be explained by the fact that they maintain a normal pattern of bcl‐2 expression.
Pseudomalignant perineurial invasion in cellular (‘infantile’) capillary haemangiomas
Authors: CALONJE E. , MENTZEL T. , FLETCHER C.D.M.
Published: April 2007

One hundred and sixty‐eight cellular (‘infantile’) capillary haemangiomas were assessed for the presence of perineurial invasion, a feature that can lead to the erroneous diagnosis of malignancy. Fourteen tumours (8%) showed unequivocal, usually prominent, involvement of small and medium sized nerves. Eleven of these lesions presented in infants at birth or shortly thereafter, two in young adults and one in a middle‐aged adult. Ten patients were females. Ten of the lesions arose in the head and neck region, one in the arm, one in the chest wall, and in two the site was not stated. Follow‐up revealed a local recurrence in only one of six cases. Histologically, all cases were typical pure capillary haemangiomas composed of lobules of small blood vessels, lined by bland endothelial cells, involving the dermis, subcutis or both. One case was an intramuscular capillary haemangioma. Long‐standing cases, especially those in adults, were less cellular, with focal fibrosis and a myxoid stroma. Neural invasion was detected either in the centre or at the periphery of tumour lobules and was characterized by the presence of variable numbers of capillaries within the perineurium and in close contact with Schwann cells. This feature was highlighted by immunostaining for S‐100 protein and EMA. In one case, extensive invasion of medium‐sized deep dermal veins was also present, focally simulating an intravascular pyogenic granuloma. This study demonstrates that perineurial invasion in infantile capillary haemangiomas is a relatively common finding and should not be regarded as evidence of malignancy.
Angiosarcoma of the larynx
Authors: SCIOT R. , DELAERE P. , DAMME B. VAN , DESMET V.
Published: April 2007

The morphological and immunohistochemical features of a laryngeal angiosarcoma are described. Initially, the tumour was interpreted as a poorly differentiated squamous cell carcinoma. The laryngectomy specimen contained an extensive and haemorrhagic tumour consisting of irregular and dissecting vascular spaces delineated by pleomorphic endothelial cells. In addition to these obvious angiosarcomatous areas, islands of more compact growing tumour cells were present, reminiscent of a poorly differentiated squamous cell carcinoma. On immunohistochemistry, the tumour cells expressed factor VIII, Ulex europaeus I lectin, CD31 and vimentin. There was no expression of cytokeratin or epithelial membrane antigen. Angiosarcoma of the larynx is very rare and should be differentiated from a pseudo‐angiosarcomatous carcinoma.
Pre‐neoplastic lesions of the prostate
Authors: PARKINSON M.C.
Published: April 2007

Acinar carcinoma of the prostate is the third most frequently registered cancer and its incidence is expected to increase as life expectancy increases. Consequently, there have been attempts to introduce possible screening programmes for early detection of prostatic carcinoma. In this context the histopathologist has a role in that potential pre‐neoplastic lesions have to be recognized. Two such pre‐neoplastic lesions in the prostate are adenomatous hyperplasia and prostatic intraepithelial neoplasia. In this article the histological features of these lesions, their differential diagnosis and their pre‐malignant potential are reviewed.
Inflammatory pseudotumour of soft tissues: a clinicopathological and immunohistochemical analysis of 18 cases
Authors: RAMACHANDRA S. , HOLLOWOOD K. , BISCEGLIA M. , FLETCHER C.D.M.
Published: April 2007

Pseudosarcomatous proliferations of myofibroblasts. fibroblasts and inflammatory cells have been reported in a wide variety of sites and are most commonly termed idammatory pseudotumours. Despite increasing recognition, the occurrence of inflammatory pseudotumour in somatic soft tissue is poorly documented, such that these lesions are commonly mistaken for a variety of benign and malignant neoplasms. This report documents our experience of 18 cases of soft tissue inflammatory pseudotumour. All arose in adults (median age 54.5 years: range 28‐83 years) and showed no sex predilection. Anatomical location was varied but the head and neck region and abdominal cavity were most common. They displayed a spectrum of histological appearances but all were characterized, to a greater or lesser extent, by an admixture of myofibroblasts and fibroblasts, most commonly arranged in short interwoven fascicles, together with a polymorphic inflammatory cell component, consisting principally of lymphocytes and plasma cells. In some cases xanthoma cells were prominent. Simple surgical excision appeared to be curative. The importance of recognizing the presence of a wide clinicopathological spectrum is emphasized and the differential diagnosis, especially from fibrohistiocytic neoplasms or Hodgkin's disease, is discussed.
Contribution of cellular infiltration to the progression of IgA nephropathy: A longitudinal, immunocytochemical study on repeated renal biopsy specimens
Authors: OOTAKA Tetsuya , SAITO Takao , YUSA Akira , MUNAKATA Takako , SOMA Jun , ABE Keishi
Published: April 2007

Summary: A retrospective immunocytochemical study was performed on repeated renal biopsy specimens from 47 patients with IgA nephropathy, 23 of whom received steroid therapy after the initial biopsy. Immune cells in renal tissues were detected by the immunoperoxidase method using monoclonal antibodies against common leukocyte antigens, T cells, B cells and monocytes/macrophages.

Overall, glomerular infiltration of total leukocytes and monocytes/macrophages was significantly correlated with proteinuria. Interstitial infiltration of total leukocytes, T cells and monocytes/macrophages was significantly correlated with histological injury and renal dysfunction. In the steroid‐treated group (group S), urinary protein and glomerular infiltration of total leukocytes and macrophages were significantly reduced at the follow‐up biopsy, while these parameters remained unchanged in the nonsteroid‐treated group (group N). In group S, interstitial infiltration of almost all of the various cell types, histological renal damage and renal function remained unchanged at the follow‐up biopsy, while group N showed a significant increase in the number of interstitial total leukocytes, T cells and macrophages and showed a significant progression of histological renal injury.

These findings suggest that glomerular immune cells, especially monocytes/macrophages, are involved in inducing proteinuria and interstitial immune cells are involved in renal deterioration. Furthermore, steroid therapy appears to reduce urinary protein and prevent the progression of tissue injury through suppression of renal infiltration of these inflammatory cells.
Local macrophage proliferation in experimental Goodpasture's syndrome
Authors: LAN Hui Y , NIKOLIC‐PATERSON David J , ATKINS Robert C
Published: April 2007

Summary: The traditional dogma that macrophages do not proliferate within inflammatory lesions has recently been challenged. We have addressed this issue in a study of experimental Goodpasture's syndrome (rat anti‐glomerular basement membrane [GBM] disease). Monocyte and macrophage proliferation was assessed during the initation and evolution of this severe inflammatory disease by expression of the proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation using twocolour immunohistochemistry. This study found that: (i) the initial accumulation of ED1+ macrophages in the kiney and lung seen during the indcution of disease resulted from blood monocyte recruitment; however, large numbers of proliferating macrophages (up to 60% of total macrophages) were present in these tissues during subsequent disease evolution; (ii) macrophage proliferation was restricted to the kidney and lung as demonstrated by the complete lack of PCNA expression and BrdU uptake by circulating monocytes and unchanged levels of resident macrophage proliferation within the spleen and liver; (iii) local macrophage proliferation within inflamed tissues was confined to cells of an ED1+ED2−ED3− phenotype indicating that they were recently arrived monocytres and not resident tissue macrophages; and (iv) proliferating macrophages within inflamed tissues were localized in focal areas of severe tissue damage. In conclusion, this study has demonstrated that local proliferation of recuited monocytes makes a major contribution to macrophage accumulation within inflamed tissues during the evolution of rat anti‐GBM disease. Furthermore, local macrophage proliferation may play an important role in the mediation of tissue injury in this disease model.
An education programme promoting organ donation for 13–14 year old schoolchildren
Authors: AGAR John WM , SIMMONDS Rosemary , HEINTZ Rosemary
Published: April 2007

Summary: Many programmes have attempted community education in organ donation. Too often these ‘preach to the converted’ or concentrate on special interest groups, thus failing to widely influence community perceptions of transplantation and organ donation.

As 13–14 year old children appear sufficiently mature to be receptive to challenging ideas yet may not yet have developed fixed biases or opinions to impair concept assimilation, an educational package dealing with dialysis/transplantation and organ donation was tested in two evenly aged, socio‐economic and sex matched student groups at this age level in a single co‐educational school. One group only was exposed to a 3 h comprehensive course in renal structure and function, dialysis and transplantation. the two groups were assessed 1 year later by questionnaire to test the retention of information and, more importantly, to compare attitudes to organ donation.

Statistically significant differences characterized the knowledge of and attitudes towards dialysis and transplantation between the two groups. In particular, the tutored group was much more likely to agree to organ donation by self (P<0.009) or by relatives (P<0.03) when compared to the untutored group.

This study demonstrates that a short, simple education course for 13–14 year old students can favourably change their perceptions and attitudes towards organ donation. the wider application of similar courses may have a positive impact upon dialysis and transplantation awareness and, ultimately, on national donor rates, becoming a useful addition to national strategies to increase organ donation.
Human renal allograft rejection: Immune mechanisms, molecular correlates and treatment strategies
Authors: SUTHANTHIRAN Manikkam , STROM Terry B
Published: April 2007

Summary:Through the release of cytokines and cell‐to‐cell interactions, a diverse assembly of lymphocytes, including CD4+ cells, CD8+ cytotoxic T cells, antibody‐forming B cells, and other pro‐inflammatory leucocytes are recruited into the anti‐allograft response. In this review, we discuss immune effector mechanisms, molecular correlates of rejection and therapeutic protocols. the recent expansion in our knowledge, coupled with the discovery and use of new immunosuppressants in the clinic, engenders optimism regarding management of allograft rejection, the most serious frequent complication in organ transplantation.
Matrix degradation in renal disease
Authors: JONES Colin
Published: April 2007

Summary: The histological appearance of the accumulation of glomerular and tubulointerstitial extracellular matrix (ECM) is a characteristic feature of progressive renal disease. the usual processes behind this finding are a combination of relative loss of parenchymal cells with respect to ECM, increased synthesis of ECM and decreased degradation of ECM. the physiology and pathophysiology of matrix degradation form the basis of tissue remodelling in general and have only been specifically studied in relation to renal disease recently. the two major ECM degrading enzyme systems (the matrix metalloproteinase (MMP), tissue inhibitor of the MMP (TIMP) system and the plasminogen activator/plasmin system) and the interaction between these systems and other non‐specific seem to have an important role in the processes causing matrix accumulation in the ageing kidney, focal sclerosis, diabetes, glomerulonephritis with matrix accumulation and tubulointerstitial disease. A pattern of changes in the expression of components of these enzyme‐inhibitor systems marked by increased TIMP‐1, increased plasminogen activator inhibitor‐1, decreased MMP‐1 and MMP‐3, and increased MMP‐2 and MMP‐9 characterized several models of glomerular and tubulointerstitial fibrosis that are associated, and perhaps caused by, transforming growth factor β. A thorough understanding of the processes controlling matrix degradation may not only be necessary to explain the pathogenesis of matrix accumulation but may also be important in attempting to reverse the processes.
Efficacy of methylcobalamin in subclinical uraemic neuropathy as detected by measuring vibration perception thresholds
Authors: KOYAMA Katsushi , YOSHIDA Atsuhiro , TAKEDA Asami , MOROZUMI Kunio , FUJINAMI Takao
Published: April 2007

Summary: Vibration perception thresholds (VPT) were measured using a new machine, the SMV‐5 (Technolog Company, Tokyo, Japan) in 25 patients receiving maintenance haemodialysis without overt uraemic neuropathy. Patients who had other medical complications such as diabetes mellitus, dialysis amyloidosis or central nervous system dysfunction or peripheral vascular disease were excluded from this study. Forty per cent of the upper extremity VPT and 68% of the lower extremity VPT of the dialysis patients were abnormal, which was defined as greater than 2s.d. above the mean of the normal subjects. the VPT of smokers (n= 7) were significantly higher than those of non‐smokers (n= 18; P<0.01). the VPT of the patients in the treated group (n= 13, including 4 smokers) improved 6 months following the initiation of methylcobalamin therapy (P<0.05). the high incidence of subclinical uraemic neuropathy led us to consider that uraemic neuropathy should be detected at an early stage. the relationship between neurologic disorders and smoking, and the efficacy of methyl cobalamin (analogue vitamin B12) in the treatment oraemic neuropathy (and in the peripheral neuropathy noted in Leber's disease) suggest that cyanide may be the uraemic toxin responsible for the neuropathy. Further studies of chronic cyanide exposure and the metabolism of cyanide in patients with uraemia are necessary.
Dialysis in developing countries: Priorities and obstacles
Authors: JHA V , CHUGH KS
Published: April 2007

Summary: The incidence and prevalence of end stage renal failure (ESRD) is unknown in the developing countries due to lack of organized registries. the vast majority of ESRD patients are unable to gain access to dialytic therapy because of poverty, ignorance and lack of healthcare delivery systems. Even those who can manage to avail themselves of maintenance dialysis facility, continue to suffer from complications of uraemia due to inadequate dialysis. Because of the high costs involved in setting up and running haemodialysis units, a sudden growth in the number of dialysis units is not expected in the near future. Continuous ambulatory peritoneal dialysis (CAPD) has yet to gain wide acceptance. A successful renal transplant remains the only viable form of renal replacement therapy. Unless the policy makers decide to make special budgetary allocations for care of ESRD in developing countries, most of the patients would continue to die without receiving the benefits of modern therapy.
Apoptosis and resolution of experimental renal infective tubulointerstitial nephritis
Authors: HEWITSON Tim D , SMITH Kenneth GC , BECKER Gavin J
Published: April 2007

Summary: Resolution of tubulointerstitial nephritis represents an important step in limiting renal fibrogenesis. However, the mechanism of this resolution remains poorly understood. to determine if apoptosis has a role in this process, we studied its incidence in an experimental model of renal infection and scarring, induced by direct inoculation of Escherichia coli into the renal cortex of Sprague‐Dawley rats. the focal lesion produced was studied in animals killed at various time points up to 100 days post inoculation. Apoptosis was identified by electron microscopy (EM) and in‐situ labelling of fragmented DNA using terminal transferasemediated deoxy‐uridine‐5′‐triphospate (UTP) nick end labelling (TUNEL). Results were compared with morphological assessment of tubulointerstitial cellularity and macrophage localization. Terminal transferasemediated UTP nick end labelling localized apoptosis to interstitial cells, tubular casts and occasional tubular epithelia and double labelling demonstrated apoptotic body incorporation in macrophages. Interstitial cellularity was maximum at day 3, decreasing significantly by 100 days (P< 0.01). the incidence of interstitial apoptosis was increased by 3 days and remained significantly higher than day 0 controls throughout (P < 0.05). Tubular cellularity was significantly less than in control animals throughout the experimental time period. Although the rate of tubular apoptosis was increased, this difference was not statistically significant. In conclusion, apoptosis may represent an important mechanism in the reduction of tubulointerstitial cellularity after experimental renal infection. This in turn, may be important in limiting subsequent interstitial scarring.
Dynamics of renal glucose reabsorption in rat
Authors: LÓPEZ‐NOVOA José M , ELENO Nelida , MARTÍNEZ‐MALDONADO Manvel
Published: April 2007

Summary: Glucose filtered load (FL), glomerular filtration rate (GFR) and tubular glucose reabsorption (TG) were simultaneously measured in the right, control kidney and in the left kidney with cortical necrosis (CN kidney) in rats with increasing plasma glucose concentrations (PG). Urinary glucose excretion starts when plasma concentrations (threshold value) averages 2.69 ± 0.20 mg/mL in the control kidney and 2.78 ± 0.16 mg/mL in the CN kidney (non significant; NS). For PG above the threshold value, increases in glucose FL were associated with increases in TG reabsorption. Maximal glucose reabsorption was not reached even when PG levels were 10 mg/mL. Moreover, there is a linear correlationship between TG reabsorbed and glucose FL in this range of PG. Among the two factors determining FL, our results support a linear correlationship between glucose reabsorption and GFR. Finally, no significant differences in tubular glucose reabsorption dynamics appears between control and CN kidney suggesting similar dynamics for glucose reabsorption in cortical and juxtamedullary nephrons.
Serum hepatocyte growth factor concentration in patients with various degrees of chronic renal failure
Authors: CHANG Hangil , OKUDA Toshihiro , NOMURA Yuji , NAGAO Tsuyoshi , NAKAMURA Toshikazu , KUROKAWA Kiyoshi , KATOH Tetsuo
Published: April 2007

Summary: Serum hepatocyte growth factor (HGF) concentrations were measured in healthy volunteers, chronic renal failure patients without renal replacement therapy and haemodialysis patients. Serum HGF concentrations in healthy volunteers, chronic renal failure patients and haemodialysis patients were 0.18 ± 0.04 (s.d.), 0.28 ± 0.06 and 0.46 ± 0.22 ng/mL, respectively. Serum HGF concentration in chronic renal failure patients was significantly higher than that in healthy volunteers. Serum HGF concentration in haemodialysis patients was significantly higher than those in healthy volunteers and chronic renal failure patients. There was no regression of serum HGF concentration on age, sex, history of haemodialysis, prehaemodialysis serum creatinine concentration, and serum tumour necrosis factor (TNF)‐α concentration. We conclude that chronic renal disease and haemodialysis therapy are contributing factors to an increased serum HGF concentration.
Glomerular stereology: Why, what and how to measure glomerular structure
Authors: CAHILL Meroë M , KETT Michellm , McCAUSLAND Jane E , ALCORN Daine , BERTRAM John F
Published: April 2007

Summary: Quantitative methods are frequently used to analyse the structure of renal glomeruli. However, on most occasions, measurements are made on glomerular profiles (the two‐dimensional samples of glomeruli seen in histological sections), and provide little or no information about the structure of whole, three‐dimensional glomeruli. Stereology is the discipline concerned with the quantitative analysis of three‐dimensional structures. With stereology one can estimate the total number of glomeruli in kidneys, as well as mean glomerular volume, the number of cells in glomeruli, and the length and surface area of glomerular capillaries. In addition to providing a means for detecting structural differences between glomeruli from different specimens, stereology provides quantitative structural information that can be correlated with quantitative physiological, biochemical and molecular data. Over the past decade we have witnessed the development of a new generation of unbiased, cost‐efficient stereological methods that are ideally suited to analysing glomeruli. Some of these methods are introduced in this review, and then three recent studies from our laboratories that successfully utilized these methods are described. These studies concerned hypertension, kidney development, and the pathogenesis of focal and segmental glomerulosclerosis.
Effect of vanadate in acute metabolic acidosis
Authors: EIAM‐ONG Somchai , CHANKASEM Kannika , CHOMDEJ Bungorn , SANGMAL Mariem , KURTZMAN Neil A. , SITPRIJA Visith
Published: April 2007

Summary: The effect of vanadate on urinary excretion of acid and electrolyte in dogs with hydrochloric acid (HCI)‐induced acute metabolic acidosis was studied. Vanadate caused no changes in systemic and renal haemodynamics, blood parameters and net acid excretion (NAE) in the control group. In the acute metabolic acidosis group, metabolic acidosis per se also had no effect on haemodymic parameters. Fractional excretion of bicarbonate was decreased, while NAE was markedly increased. Following vanadate treatment, acute acid‐loaded animals showed an increase in mean arterial pressure (MAP), but a decreased glomerular filtration rate and effective renal plasma flow. These animals had reduced NAE compared to that seen with HCI alone. Thus, vanadate impaired the renal adaptive responses to acute metabolic acidosis. the decreased NAE induced by vanadate might be caused by its known inhibitory effect on hydrogen‐potassium‐adenosine triphosphatase (H‐K‐ATPase) and sodium‐potassium‐adenosine triphosphatase (Na‐K‐ATPase), and by renal vasoconstriction.