bluuebunny/crossref_metadata_2025 huggingface dataset:
CD30 (Ki‐1) expression in adult T‐cell leukaemia/lymphoma is associated with distinctive immunohistological and clinical characteristics
Authors: TAKESHITA M. , AKAMATSU M. , OHSHIMA K. , KOBARI S. , KIKUCHI M. , SUZUMIYA J. , UIKE N. , OKAMURA T.
Published: April 2007

Twenty‐one patients with CD30 (Ki‐1) positive lymphoma were studied from a group of 91 patients with adult T‐cell leukaemia/lymphoma. The patients were grouped into three types: diffuse CD30 positive anaplastic large cell lymphoma in 11 patients (group 1); pleomorphic type lymphoma with diffuse CD30 expression in five patients (group 2); and pleomorphic type lymphoma with positive CD30 expression in large cells but negative in medium‐sized and small cells in five patients (group 3). The patients with diffuse CD30 positive lymphomas (groups 1, 2) frequently presented with extranodal tumours (68.8%) and lymph node enlargement greater than 2 cm in diameter (50%), and rarely with leukaemic changes, bone marrow involvement and hypercalcaemia (one case of each). Patients in group 3 rarely had extranodal tumours, but had frequent leukaemic changes. Expression of intercellular adhesion molecule (ICAM‐1; CD54) by the lymphoma cells in 13 patients (81.3%) with diffuse CD30 positive lymphomas, was significantly higher than that in 33 patients (9.1%) with CD30 negative adult T‐cell leukaemia/lymphomas. No positive reaction for epithelial membrane antigen (EMA) was found in the lymphoma cells of CD30 positive cases. The overall survival in patients with diffuse CD30 positive lymphomas was better than that of CD30 negative adult T‐cell leukaemia/lymphoma patients, but showed no significant difference. These findings suggest that diffuse CD30 positive adult T‐cell leukaemia/lymphoma has unusual clinical and immunohistological findings. It is also speculated that local tumour formation and leukaemic changes in such diffuse CD30 positive cases are influenced by CD54 (ICAM‐1) expression by the lymphoma cells.
Transthyretin and cystatin C are catabolized in proximal tubular epithelial cells and the proteins are not useful as markers for renal cell carcinomas
Authors: JACOBSSON B. , LIGNELID H. , BERGERHEIM U.S.R.
Published: April 2007

Ten human kidney specimens and thirty‐two renal cell carcinomas were investigated for the presence of transthyretin mRNA and cystatin C mRNA using Northern blot analysis. Five of ten kidney specimens and 15 of 32 renal carcinomas were also immunohistochemically investigated for the presence of the corresponding proteins. Transthyretin mRNA could not be detected in any of the normal or neoplastic tissue preparations, whereas low amounts of cystatin C mRNA were found in nine of ten normal kidneys and in 24 of 32 renal cell carcinomas. Immunoreactive transthyretin and cystatin C were present in proximal tubular epithelial cells of all kidney specimens, whereas neither of the proteins was detected in the tumour cells of the renal carcinomas. Immunoreactive cystatin C was, however, demonstrated in scattered monocyte/macrophage‐like cells. We conclude that the presence of immunoreactive transthyretin and cystatin C in proximal tubular cells of the kidney is most likely due to reabsorption of the proteins from the primary urine. The small amounts of cystatin C mRNA in some of the normal and neoplastic renal preparations are probably due to cystatin C synthesis in macrophages. Transthyretin has been recommended as an immunohistochemical marker for renal cell carcinomas. Our results, however, clearly indicate that neither transthyretin nor cystatin C constitutes a useful marker for such neoplasms.
Post‐operative spindle cell nodule of the vulva
Authors: MANSON C.M. , HIRSCH P.J. , COYNE J.D.
Published: April 2007

A case of post‐operative spindle cell nodule arising in the vulva of a 33‐year‐old woman is reported and the relevant literature reviewed. This is an uncommon, benign lesion which develops soon after a surgical procedure and which is composed of mitotically active spindle cells, causing possible confusion with sarcoma. Knowledge of the clinical history and an awareness of the existence of such lesions is necessary in order to avoid misinterpretation.
Antibodies to cytokeratins bind to epitopes in human uterine smooth muscle cells in normal and pathological pregnancies
Authors: STIEMER B. , GRAF R. , NEUDECK H. , HILDEBRANDT R. , HOPP H. , WEITZEL H.K.
Published: April 2007

Cytokeratin antibodies have been widely used for the identification of trophoblast cells in the placental bed, following their invasion from the developing conceptus. Their identification centres upon the expression of cytokeratin in epithelial cells, from which trophoblast cells are derived. Our recent observations indicate that this strict relationship may be more complex than was thought. Cryostat and paraffin sections of human decidua and myometrium, taken from the placental bed and the uterotomy cut, were examined immunocytochemically for cytokeratins using ten antibody clones selected to identify different cytokeratin proteins and antigenic epitopes. Biopsy specimens were obtained from normal and pathological pregnancies (pre‐eclampsia, fetal retardation, amnioninfection, hysterorrhexis, placenta praevia) at the time of caesarean section (26–41 weeks of pregnancy). Antibodies against nine clones, CAM 5.2, MNF 116, AE1/AE3, CK5, KS‐B17.2, CY‐90, M20, E3, and 34βE12 identified, as expected, syncytial giant cells and mononuclear trophoblasts within the placental bed and glandular epithelial cells throughout the uterus. In addition, they stained numerous fusiform cells that were classified by established criteria to represent smooth muscle cells, both within blood vessels and myometrium. No staining differences were observed between normal and pathological disorders. These results indicate that cytokeratin antibodies CAM 5.2, MNF 116 and AE1/AE3, and other antibodies targeting proteins 8 and 18, cross‐react with epitopes expressed in cells other than giant trophoblastic cells and mononuclear trophoblasts in the uterus and, thus, caution has to be used when such antibodies are used for the diagnostic characterization of tissues related to the placental bed.
Histological study of oxalosis in the eye and adnexa of AIDS patients
Authors: PECORELLA I. , McCARTNEY A.C.E. , LUCAS S. , MICHAELS L. , CIARDI A. , TONDO U. DI , GARNER A.
Published: April 2007

Review of a series of 98 eyes removed at autopsy from 86 AIDS patients identified 12 cases (14%) showing varying degrees of microscopic calcium oxalate deposition. The oxalate crystals were birefringent using polarisation microscopy and were stained histochemically by the silver nitrate‐rubeanic acid method (Yasue), a stain considered to be specific for calcium oxalate. In two cases, the deposition was extensive and involved the surface of the ciliary processes, ciliary body and pars plana of the retina, the retinal and optic nerve blood vessel wall, a few retinal pigment cells, and the anterior inner sclera. A lesser degree of intraocular involvement was observed in the remaining 10 cases. In all but two eyes, where a peripheral active area of cytomegalovirus retinitis was present, no other significant microscopical abnormality was found. Clinically, these patients were asymptomatic. At autopsy, oxalate deposits were found in the kidney and/or thyroid in seven of the patients.
Recurrent thymoma: evidence for histological progression
Authors: PESCARMONA E. , RENDINA E.A. , VENUTA F. , RICCI C. , BARONI C.D.
Published: April 2007

The clinicopathological features of nine cases of recurrent thymomas have been studied. At presentation, all cases were histologically classified as thymomas with cortical differentiation, including predominantly cortical thymoma, cortical thymoma and well‐differentiated thymic carcinoma. In five cases the morphological features of the recurrence(s) were suggestive of a histological progression of the tumour from predominantly cortical thymoma to cortical thymoma and/or well‐differentiated thymic carcinoma, usually associated with a more advanced clinical stage, the latter indicating a clinical progression. These findings suggest that all types of thymoma with cortical differentiation are histologically and histogenetically related neoplasms, associated with a more aggressive clinical behaviour and a significant risk of recurrence. The overall outcome of patients with recurrent thymoma in this series was poor, since six patients (66.6%) died due to the disease, 2–14 years after the first diagnosis. The clinical implication of our findings is that thymomas with cortical differentiation always need careful follow‐up, even in those cases which are not obviously invasive at onset.
Rheumatic Aschoff nodules revisited: an immunohistological reappraisal of the cellular component
Authors: FRASER W.J. , HAFFEJEE Z. , COOPER K.
Published: April 2007

Rheumatic fever is still the leading cause of acquired heart disease in children and young adults in developing countries. Recent reports have documented a rising incidence of rheumatic fever in both the USA and Europe. The disease is characterized by specific lesions in the heart muscle and valves called Aschoff nodules. The Aschoff nodule has been neglected in the last few decades as most of the studies were conducted in the 1960s on autopsy tissues. This study examines Aschoff nodules using heart valve material obtained at valve surgery with updated commercially available immunohistochemical antibodies to determine the phenotypic characteristics of the cells involved in the formation of these lesions. Fifteen cases of rheumatic valvulitis, as indicated by the presence of Aschoff nodules, were examined. The Anitschkow and Aschoff cells stained prominently with macrophage markers. Three stages of nodules with Aschoff and Anitschkow cells were identified: stage 1, central fibrinoid necrosis without lymphocytes, stage 2 with occasional T lymphocytes (< 10) and stage 3 with lymphoid aggregates containing both T‐ and B‐lymphocytes (with occasional admixed macrophages). We propose that the stage 1 lesion is the earliest granulomatous stage with the lymphoid aggregates being a later stage in the development of Aschoff nodules. The Aschoff and Anitschkow cells demonstrated mitotic activity and stained with antibodies to the proliferation cell nuclear antigen (PCNA) suggesting that the multinucleated giant cells may be formed, at least partially, by nuclear division rather than fusion.
Combination of Hodgkin's disease and diffuse large cell lymphoma: an in situ hybridization study for immunoglobulin light chain messenger RNA
Authors: HELL K. , HANSMANN M.L. , PRINGLE J.H. , LAUDER I. , FISCHER R.
Published: April 2007

It is not clear whether the rare combination of Hodgkin's disease with non‐Hodgkin lymphomas are true composite lymphomas or differentiation stages of one tumour cell clone. We used in situ hybridization and immunohistochemistry for the demonstration of immunoglobulin light chains in order to investigate the relationship between the two lymphoma components. In three cases of nodular lymphocyte predominance Hodgkin's disease combined with diffuse large B‐cell lymphoma the Hodgkin cells, as well as the tumour cells in the diffuse large B‐cell lymphoma, showed the same messenger RNA for one light chain. Thus, using in situ hybridization in nodular lymphocyte predominance Hodgkin's disease combined with diffuse large B‐cell lymphoma in a small number of cases a possible genetic relationship between the two components could be shown. In nodular sclerosis combined with diffuse large B‐cell lymphoma, in situ hybridization did not support a common clonal origin of both tumour parts. However, a unique clonal derivation cannot be excluded by the techniques applied.
Inflammatory leiomyosarcoma: a morphological subgroup within the heterogeneous family of so‐called inflammatory malignant fibrous histiocytoma
Authors: MERCHANT W. , CALONJE E. , FLETCHER C.D.M.
Published: April 2007

Twelve cases of inflammatory leiomyosarcoma are presented. These tumours arose in the deep soft tissues of the trunk and proximal limbs. The age of the patients ranged from 13–53 years (median 36 years); there was an approximately equal sex ratio. Follow‐up data was available for nine patients (mean duration 3.3 years); local recurrence occurred in three and lung metastases in one. Lesions were spindle cell neoplasms with fascicular areas which occupied between 5% and 80% of the tumour. Areas with a distinct storiform pattern were also seen in 10 cases. A prominent inflammatory cell component was evident in all tumours, often masking the neoplastic spindle cells. Histiocytes were identified in all cases, with aggregates of xanthoma cells seen in eight tumours. In 10 cases there was also a dense lymphoid infiltrate and in two a marked polymorphonuclear leukocyte infiltrate was evident. Immunohistochemistry showed in all tumours that the spindle cells stained positively for myogenic markers (8 of 12 positive for desmin, 10 of 12 for alpha smooth muscle actin and 11 of 12 for HHF‐35). CD68 was expressed by the histiocytic infiltrates. Many of these tumours were diagnosed initially as inflammatory malignant fibrous histiocytoma. We provide evidence that at least one subset of neoplasms, which would have been formerly classified under this rubric, in fact show smooth muscle differentiaton. Further studies are required to investigate the possibility that other tumour types or lines of differentiation may be present within the category of so‐called inflammatory malignant fibrous histiocytoma.
Yolk sac tumour of the ear
Authors: FUKUNAGA M. , MIYAZAWA Y. , HARADA T. , USHIGOME S. , ISHIKAWA E.
Published: April 2007

We report the second known case of yolk sac tumour of the external auditory canal, occurring in an eight‐month‐old girl. The excised tumour demonstrated histopathological and immunohistochemical features identical to those of yolk sac tumours of gonadal origin. The tumour was aneuploid by flow cytometry. The patient received chemotherapy post‐operatively and has had no evidence of disease 13 months after surgery.
Female adnexal tumour of probable Wolffian origin
Authors: RAHILLY M.A. , WILLIAMS A.R.W. , KRAUSZ T. , NAFUSSI A. AL
Published: April 2007

The clinical and pathological features of three adnexal tumours of probable Wolffian origin are reported. One case was an incidental finding in a patient who died from ovarian carcinoma; in the other two cases the patients presented with lower abdominal pain. The three tumours were well‐circumscribed, solid masses arising in the leaves of the broad ligament and histological examination showed bland epithelial cells forming tubular, solid and microcystic patterns. The immunohistochemical profile of the tumours was similar to that of Wolffian duct remnants. They co‐expressed cytokeratin and vimentin and lacked epithelial membrane antigen (EMA) reactivity, in contrast to tumours of Müllerian origin which usually express EMA. The differential diagnosis of female adnexal tumours is discussed.
DNA flow cytometric analysis in renal neoplasms associated with acquired renal cystic disease
Authors: MALLOFRÉ C. , ALMIRALL J. , CAMPISTOL J.Ma , MUNTANÉ J. , CARDESA A.
Published: April 2007

In order to better understand the potential malignancy of renal neoplasms arising in patients with acquired renal cystic disease and to try and establish differences from other renal tumours we analysed DNA ploidy as well as the level of S‐phase fraction in 11 neoplasms associated with acquired cystic disease by means of flow cytometry. The results were correlated with known prognostic factors such as nuclear grade, size and stage, as well as the clinical behaviour of the tumours. We found a close relationship between DNA aneuploidy and high S‐phase fraction and a poor clinical outcome. We also found some differences in the DNA ploidy profile of these tumours when compared with those reported in other renal neoplasms.
The choroid plexus carcinomas of childhood: histopathology, immunocytochemistry and clinicopathological correlations
Authors: NEWBOULD M.J. , KELSEY A.M. , ARANGO J.C. , IRONSIDE J.W. , BIRCH J.
Published: April 2007

Anaplastic choroid plexus carcinoma is a tumour with a predilection for the posterior fossa of infants and can be difficult to distinguish histologically from medulloblastoma without the aid of immunocytochemistry using a panel of antibodies. Of a series of 17 choroid plexus carcinomas (five of which were classed as moderately differentiated and 12 as anaplastic) 17 expressed antigens to transthyretin, transferrin and cathepsin and 16 expressed carbonic anhydrase II. Eleven expressed at least one epithelial marker (cytokeratin or epithelial membrane antigen). In contrast, none of six medulloblastomas expressed epithelial markers, transrythetin, carbonic anhydrase II or transferrin, though three were positive with antibodies to cathepsin.
Keratin expression in cutaneous lichen planus
Authors: SCHOFIELD J.K. , BERKER D. DE , MILLIGAN A. , ROHLOFF W. , MARREN P. , DAVIES M.G. , BURGE S. , GRAHAM‐BROWN R. , LEIGH I.M.
Published: April 2007

The characteristic expression of keratins by keratinocytes is well documented. A typical ‘hyperproliferative’ profile of epidermal keratin expression occurs in psoriasis, wound healing and warts. This study analyses keratin expression in cutaneous lichen planus to determine abnormalities of differentiation occuring in this inflammatory disorder. Using a panel of monoclonal antibodies 28 samples (20 patients) were studied. The results showed that squamous differentiation was unaffected, with keratins K1 and K10 being expressed normally for the site sampled. The main abnormalities included extension of reactivity of the basal cell marker, LH8, into the suprabasal compartment. Keratin K17, usually restricted to adnexal structures, was variably expressed in the basal and suprabasal layers of the interfollicular epithelium of affected epidermis. Keratins K6 and K16, found suprabasally in hyperproliferative states, were detected both basally and suprabasally in all diseased samples. The keratin profile in lichen planus is analogous to the wound healing response. Suprabasal keratin K17 is found in psoriasis, wound healing and viral warts so the changes in keratin K17 may reflect hyperproliferative changes. It is likely that the changes in epidermal keratin expression are due to up‐regulation of specific keratin genes by the production of cytokines and inflammatory mediators from the lymphocytic infiltrate typical of lichen planus.
Alphafetoprotein‐producing gastric adenocarcinoma
Authors: PETRELLA T. , MONTAGNON J. , ROIGNOT P. , NIEUVENHUYSE A. VAN , MATAGRIN C. , MICHIELS‐MARZAIS D. , DUSSERRE‐GUION L. , SPIEKERMANN C.
Published: April 2007

We report a rare gastric tumour characterized morphologically by its hepatoid features and alpha‐fetoprotein production and which presented clinically with gastric haemorrhage. Gastric fibroscopy showed a bleeding tumour of the antrum. The microscopic appearance of the tumour showed two different patterns. The most extensive presented hepatoid features. The second pattern showed undifferentiated features. The tumour cells showed immunohistochemical positivity for alphafetoprotein, EMA and p53 protein; 37% were aneuploid with a DNA index of 1.46. The serum level of alphafetoprotein was not measured before the gastrectomy but after ten days it was elevated at 1070ng/ml. The patient died 6 months after the admission. This case provides, for the first time, information on the DNA content and the p53 expression of this unusual and aggressive variant of gastric adenocarcinoma.
The polymerase chain reaction in histopathology
Authors: PAN L.X. , DISS T.C. , ISAACSON P.G.
Published: April 2007

Thanks to the advent of the polymerase chain reaction (PCR) molecular genetic study of histological samples is now a relatively straightforward task and the vast histopathology archives are now open to molecular analysis. In this review we outline technical aspects of PCR analysis of histological material and evaluate its application to the diagnosis and study of genetic, infectious and neoplastic disease. In addition, we describe a number of newly developed methods for the correlation of PCR analysis with histology, which will aid the understanding of the molecular basis of pathological processes.
Low grade fibromyxoid sarcoma: clinicopathological analysis of eleven new cases in support of a distinct entity
Authors: GOODLAD J.R. , MENTZEL T. , FLETCHER C.D.M.
Published: April 2007

Low grade fibromyxoid sarcoma is a recently recognized, uncommon soft tissue neoplasm with a tendency to develop in deep soft tissue of young adults. Diagnostic criteria have not been well defined and this tumour has not been widely accepted as a distinct entity. Eleven new cases are reported here for which reproducible histological features are described and in which the immunohistochemical profile of the tumour cells is documented for the first time. Ten of the eleven patients were male and the majority were young or middle‐aged adults (median age 45 years). All except one of the tumours were situated in deep soft tissue. Lower limb (four cases) and chest wall (three cases) were the commonest primary sites; one case each arose in the groin, buttock, axilla and retroperitoneum. Follow‐up (median duration 6 years) was available in nine patients. Six developed local recurrence and in five cases recurrences were multiple. Pulmonary metastasis occurred in one patient. All tumours were characterized by the presence of bland spindle cells, showing a mainly whorled or focally linear arrangement, set in alternating areas with a fibrous or myxoid stroma. Tumour cells were small, spindle to stellate, with poorly defined, palely eosinophilic cytoplasm and hyperchromatic ovoid nuclei. Most tumour cells showed strong staining with antibodies to vimentin, while occasional cells stained positively for actin, desmin and cytokeratin, in keeping with focal myofibroblastic differentiation. Ultrastructural examination in one case revealed features of fibroblasts. Careful consideration of the morphological and immunohistochemical features of these tumours permits a positive diagnosis of low grade fibromyxoid sarcoma and allows its distinction from a number of other benign and malignant soft tissue neoplasms.
Gastric schwannoma—a clinicopathological analysis of six cases
Authors: SARLOMO‐RIKALA M. , MIETTINEN M.
Published: April 2007

Six gastric schwannomas found among 150 mesenchymal tumours of the gastrointestinal tract were analysed clinically, histologically and immunohistochemically. These tumours occurred in the wall of stomach in middle‐aged patients, five women and one man, and measured 2–9 cm in diameter. Follow‐up from 3 to 24 years showed no recurrences or metastases. Histologically, all tumours were composed of spindle cells with vague nuclear palisading and variably myxoid stroma. One case showed a multinodular pattern of growth, reminiscent of plexiform neurofibroma. In all cases, there was a peripheral cuff‐like B‐lymphocyte infiltration with germinal centers in two cases. None of the tumours showed mitotic activity. Immunohistochemically, the tumour cells were positive for S‐100 protein and focally for GFAP and CD57 (Leu 7). They were negative for desmin and actin, unlike true leiomyomas, and negative for CD34, unlike most gastrointestinal stromal tumours that were examined for comparison. Electronmicroscopy of three cases showed complex cell processes surrounded by prominent basement membranes, while myofilaments were not present. These cases show that schwannomas can be identified as rare, benign gastrointestinal tumours which probably arise from the gastrointestinal autonomic nervous system.
A comparative immunohistochemical study of malignant mesothelioma and renal cell carcinoma: the diagnostic utility of Leu‐M1, Ber EP4, Tamm‐Horsfall protein and thrombomodulin
Authors: ATTANOOS R.L. , GODDARD H. , THOMAS N.D. , JASANI B. , GIBBS A.R.
Published: April 2007

Metastatic renal cell carcinoma has occasionally been reported to mimic malignant pleural mesothelioma. Morphologically, histochemically and immunohistochemically, similarities in the two tumours exist making their differentiation difficult, particularly in biopsy specimens. The aim of this study was to make a comparative immunohistochemical analysis of the two tumours by use of a panel of four antibodies (Leu M1; Ber EP4; thrombomodulin and Tamm‐Horsfall protein). Their suitability in differentiating between the two tumours was assessed. We examined 20 cases of renal cell carcinoma and 20 cases of malignant pleural mesothelioma. On immunostaining with Leu M1, 14 of 20 renal cell carcinomas were positive, yielding 70% sensitivity and 95% specificity and one of 20 mesotheliomas. In comparison, Ber EP4 antibody stained only seven of 20 of the renal cell carcinomas. In addition, it was noted that four tubulopapillary pattern renal cell carcinomas stained positively with both anti‐Leu M1 antibody and Ber EP4 antibody. Thrombomodulin immunostaining was present in 11 of 20 mesotheliomas (55% sensitivity and demonstrated 95% specificity) and one of 20 renal cell carcinomas. For epithelial mesotheliomas only, thromobomodulin staining was identified in 10 of 14 cases. In the differentiation of renal cell carcinoma from epithelial mesothelioma we recommend the use of Leu M1 and thrombomodulin as diagnostically useful markers. None of the antibodies used in this study was effective in distinguishing sarcomatoid renal cell carcinoma from sarcomatous mesothelioma. Tamm‐Horsfall protein showed little diagnostic utility in differentiating the two tumours.
Monosomy 22 in a malignant peripheral nerve sheath tumour of the kidney in childhood: a genetic link with other malignant paediatric renal neoplasms?
Authors: SCIOT R. , CIN P. DAL , FLETCHER C.D.M. , WEVER I. DE , VOS R. DE , DAMME B. VAN , BERGHE H. VAN DEN
Published: April 2007

A recurrent malignant spindle cell neoplasm of the kidney, occurring in a 11‐year‐old girl and corresponding to a malignant peripheral nerve sheath tumour is reported. The neurogenic differentiation was substantiated by the presence of PGP 9.5 neurofilament and S‐100 protein positivity and by the ultrastructural features. Cytogenetic analysis revealed monosomy of chromosome 22 in the tumour while the constitutional karyotype was normal. Primary malignant peripheral nerve sheath tumour of the kidney is extremely rare and should, on morphology, be differentiated from stromal predominant Wilms' tumour and clear cell sarcoma of the kidney. Involvement of chromosome 22 has been described in a number of malignant renal tumours of childhood, such as Wilms' tumour (deletion), clear cell sarcoma (translocation), and rhabdoid tumour (deletion and translocation), thus suggesting common molecular mechanisms in pediatric malignant renal tumours.
Pathogenesis of hepatitis C virus‐associated glomerulonephritis
Authors: JOHNSON Richard J , ALPERS Charles E , STEHMAN‐BREEN Catherine , WILLSON Richard , COUSER William G
Published: April 2007

Summary: Hepatitis C virus (HCV), in addition to causing both acute and chronic liver disease, may also be associated with several immunologically‐mediated syndromes, particularly cryoglobulinaemia and membranoproliferative glomerulonephritis. Although the glomerulonephritis may be a feature of a systemic cryoglobulinaemic syndrome, it may also present as a primary renal disease without evidence of vasculitis or liver disease. Most of these latter patients, however, will have detectable cryoglobulinaemia either at the time of presentation or with continued observation. In this review, we discuss the pathogenesis of the glomerular disease. Most evidence supports the hypothesis that HCV associated glomerular disease results from the deposition of circulating immune complexes that are usually cryoprecipitable and which contain HCV, anti‐HCV IgG, and rheumatoid factors. However, HCV antigens have yet to be identified in glomerular biopsies. This has raised the possibility that other pathogenic mechanisms may be involved, including auto‐antibodies directed against glomerular antigens and factors related to chronic liver disease. Further studies are necessary to fully elucidate the pathogenesis of this recently recognized disease.
Eicosanoid production and levels of newly characterized eicosanoid‐forming enzymes in glomeruli and tubules of rat kidneys
Authors: YANAGISAWA Hiroyuki , MORRISSEY Jerry , KURIHARA Nobutaka , WADA Osamu , KLAHR Saulo
Published: April 2007

Summary: We examined the production of prostaglandin (P0) E2, 6‐keto PGF1α and thromboxane (Tx) B2, the mass of cyclooxygenase (COX) isoenzymes and the activities of phospholipases A2 and C in glomeruli, cortical tubules and medullary tubules of rat kidneys. Medullary tubules produced significantly greater amounts of PGE2, 6‐keto PGF1α. and TxB2 than glomeruli or cortical tubules. the most abundant eicosanoid in medullary tubules was 6‐keto PGF1α. By contrast, glomeruli and cortical tubules predominantly produced POE2 (glomeruli > cortical tubules). Levels of COX 1 were markedly greater in medullary tubules than in glomeruli or cortical tubules. Glomeruli had significantly greater amounts of COX 1 than cortical tubules. Detectable amounts of COX 2 were not present in the three preparations. the activity of phospholipase (PL) A2 against phosphatidyicholine (PC) was significantly greater in tubules (medullary tubules > cortical tubules) than in glomeruli. By contrast, there was a significant increase in the activity of PLA2 against phosphatidylethanolamine (PE) in glomeruli as compared to tubules (medullary tubules > cortical tubules). the activity of PLC was the Weatest in medullary tubules. Glomeruli had significantly greater activity of PLC than cortical tubules. the order of magnitude for the total activity of the three phospholipases in membranes was medullary tubules> glomeruli> cortical tubules. the total production rate of POE2, 6‐keto PGF1α and TxB2 was in parallel with the amount of COX 1 and the total activity of membranous phospholipases A2 and C in the three preparations. In conclusion, there are differences in the production of PGE2, 6.‐keto PGF1α and TxB2, the ainount of COX 1 and the activities of phospholipases A2 andC among glomeruli, cortical tubules and medullary tubules of rat kidneys; and the different aspects of COX 1 and phospholipases A2 and C have a key role in the control of eicosanoid production in the three preparations.
Effects of renal denervation on cyclosporin induced hypertension in the Wistar rat
Authors: MARTIN Allison , LI Ming , TURNER Steven W. , WHITWORTH Judith A.
Published: April 2007

Summary: The effects of renal denervation were examined in cyclosporin A (CyA) treated Wistar rats 14 days prior to 1 day prior to and 10 days after CyA was administered. the rise in blood pressure was attenuated when the renal denervation was performed 1 day prior to and 10 days after administration, but not 14 days prior to CyA, presumably reflecting re‐innervation of the kidney. Plasma renin activity (PRA) was increased by CyA 10 mg/kg per day and 20 mg/kg per day, but decreased by renal denervation 1 day prior to CyA. Plasma creatinine was increased by CyA at 10 mg/kg per day and decreased by renal denervation 1 day prior to CyA. These data support the notion that renal sympathetics play a role in CyA induced hypertension.
Ca antagonist ameliorates glomerular injury via suppression of glomerular hypertrophy in spontaneously hypertensive rats
Authors: CHIMATA Minoru , NAGASE Mitsumasa
Published: April 2007

Summary: A study was conducted to determine whether calcium blockers (CCB) have renoprotective effects, and if so to elucidate the mechanisms of such effects.

A total of 30 uninephrectomized (UNX) spontaneously hypertensive rats (SHR), 5 weeks of age, were divided into three groups. Group 1 was fed a diet containing 0.01% manidipine and 8% NaCl, while groups 2 and 3 were fed diets containing only 8 and 0.5% NaCl, respectively. Feeding of these diets began 7 days after UNX (experimental day 0). Bodyweight, urinary protein /24 h, urinary sodium excretion/24 h, and food intake were measured at certain time intervals.

At time of death (day 9 or 21), estimations of inulin clearance (Cin) and morphological evaluations, determination of glomerular sclerosis index (GSI), tubulointerstitial index (TII) and glomerular volume were performed.

Urinary protein was significantly higher in groups 1 and 2 than in group 3 from day 7 onward, but did not differ between the former two groups. Cin in group 2 was higher than in groups 1 and 3 on day 9, but declined to lower levels than in groups 1 and 3 by day 21. There was no difference in Cin between group 1 and group 3 on day 21. Morphometry (GSI and TII) revealed that renal lesions were more progressive in group 2 than in group 1. Glomeruli in group 2 were markedly larger than those in group 1, but no difference in glomerular volume was noted between groups 1 and 3.

Our findings suggest that CCB prevent progression of renal injury induced by accelerated hypertension in UNX SHR. the mechanisms of prevention may, at least in part, be related to suppression of glomerular hypertrophy. Inhibition of renal injury can be achieved without significant reduction of proteinuria.
Treatment of crescentic glomerulonephritis
Authors: BOLTON W KLINE
Published: April 2007

Summary: Acute crescentic‐rapidly progressive glomerulonephritis is an uncommon but devastating disease which comes in several forms. That associated with anti‐glomerular basement membrane (GBM) antibodies is most vexing to treat and has by far the worst prognosis. Despite conventional wisdom that plasma exchange and immunosuppression are optimal therapy, the cost constraints and issues raised in the present review suggest that this needs to be readdressed. Non‐anti‐GBM disease appears to respond well to aggressive immunosuppression and/or plasma exchange. A possible zided benefit of plasma exchange in patients with vasculitis on dialysis needs to be further addressed, especially in terms of a possible differential effect of very large doses of pulse methylprednisolone (30 mg/kg) as opposed to smaller doses.
Extracellular matrix components in Kimmelstiel Wilson nodules
Authors: BIRCHALL IE , CHEN YP , KINCAID‐SMITW P , BECKER GJ
Published: April 2007

Summary: The distribution of collagen types I, III, IV, V, VI, fibronectin laminin, tenascin, heparan sulfate proteoglycan and chondroitin sulphate proteoglycan was examined by light microscopy immunocytochemistry (ICC) in paraffin‐embedded renal biopsies with nodular diabetic glomeruloscierosis. Immunoglobulin A, G and M, complement (C3c and C1q), fibrinogen and k and γ light chain deposition was also sought by ICC in the same tissue.

Kimmelstiel Wilson (KW) nodules were graded as either evolving (>3 nuclei present +/ ‐ fibrillary appearance) or as late stage (amorphous and acellular). the extracellular matrix (ECM) components present in the evolving KW nodules were the same as those present in normal mesangial matrix but with an increased density. Late stage nodules displayed negative binding for all antibodies in their core with accentuated expression of the normal mesangial matrix components together with complement and 1gM at their periphery. Occasionally, when ruptures in Bowman's capsule (BC) were detected and adhesions between the capsule and the nodular tuft occurred, the interstitial collagens I and III were detected within laminations of Bowman's capsule, in Bowman's space, at adhesion sites and within some nodules.

The results suggest nodular lesions are initially formed by aggregation and/or increase in the normal components of mesangial matrix. the normal mesangial matrix constituent proteins are subsequently relocated to the periphery by amorphous material in which these ECM components are not detected. When BC is disrupted, interstitial collagens I and III may appear in Bowman's space and within nodules.
Prevention of pre‐eclampsia in high risk women with renal disease: A prospective randomized trial of heparin and dipyridamole
Authors: KINCAID‐SMITH P , NORTH RA , FAIRLEY KF , KLOSS M , IHLE BU
Published: April 2007

Summary: Twenty‐one women with primary glomerulonephritis and a history of a poor outcome in previous pregnancies were randomized to receive heparin, 15 000 units subcutaneously and dipyridamole, 400 mg daily (n= 10) or no treatment (n= 11) from 14 weeks of gestation. the women were well matched in terms of the type of underlying glomerulonephritis and previous pregnancy complications. the treated group showed a significantly lower incidence of hypertension (P<0.03) and of overall maternal complication (P<0.03). the days spent in hospital prior to delivery were 18 in the treated group and 27 in the control group (P<0.01). In all other parameters which were measured the outcome was better in the treated group although these did not achieve statistical signficance. In the control group the pregnancy complications were similar to those in previous pregnancies but very few complications occurred in treated patients. Heparin and dipyridamole were used because of the activation of coagulation in preeclampsia and because of the prominence of fibrin in renal and uterine vessels in pre‐eclampsia. As heparin suppresses both the action and the production of endothelin, the benefit of treatment could have reflected endothelin inhibition.
Treatment of Australian Aboriginals with end‐stage renal disease in the top end of the Northern Territory: 1978–93
Authors: HOY Wendy E , MATHEWS John D , PUGSLEY David J
Published: April 2007

Summary: We describe the treatment of Australian Aboriginals with end‐stage renal disease (ESRD) in the Top End of the Northern Territory from 1978 to 1993. Eighty‐three Aboriginals and 44 non‐Aboriginals were accepted into the programme. the average annual incidence of ESRD for Aboriginals in 1988–93 was 440 per million (pm), or 17.4 times that of non‐Aboriginals.

Aboriginals were 20 to 30 years younger than non‐Aboriginals at start of treatment, and there was an excess of females, in contrast with a male excess among non‐Aboriginals. Aboriginals had a higher proportion of ESRD attributed to glomerulonephritis and to diabetes, and 5% had amyloid associated with chronic infections.

Most Aboriginals with ESRD received haemodialysis, and a few received peritoneal dialysis. Only 23% received transplants, compared with 48% of non‐Aboriginals, and graft and patient survival after transplant was poor for Aboriginals. A sequence of non‐compliance, chronic rejection, intensified immunosuppression and exacerbated co‐morbidities was a common cause of death.

Many Aboriginals with ESRD had serious co‐morbidities, especially chronic infections and alcohol abuse; these frequently precluded transplant and were often the ultimate cause of death. Withdrawal from treatment was the cause of death in 23% of Aboriginals, compared to only 6% of non‐Aboriginals, and usually reflected poor tolerance of, and compliance with, treatment and a lack of social support.

High rates of albuminuria and clinical nephropathy in Aboriginals are compatible with their high ESRD rates. End stage renal disease treatment choices and outcomes are related largely to their profoundly inferior health status and socioeconomic deprivation.

A 2.5‐fold increase in ESRD among Aboriginals is projected by the year 2000. Precursors of ESRD must be studied, and screening and renoprotective treatment introduced, along with intensified efforts to improve the health and welfare of the entire Aboriginal population.
Expression of 90‐kDa heat‐shock protein within cellular crescents in human diseased kidneys
Authors: KOMATSUDA Atsushi , WAKUI Hideki , IMAI Hirokazu , MIURA Akira B , ITOH Hideaki , TASHIMA Yohtalou
Published: April 2007

Summary: We previously reported the induction of 90 kDa heat‐shock protein (HSP90) in rat kidneys with cisplatin‐induced acute tubular injury, gentamicin‐induced acute renal failure and ischaemia‐induced acuterenal failure. In the present study, we examined the expression of HSP90 in normal and diseased human kidneys. the 90‐kDa heat‐shock protein (HSP90) from mouse brains was purified, and a specific antibody against the protein in a rabbit was produced. This antibody cross‐reacted with human renal HSP90 on immunoblot analysis. Using this antibody we observed the intrarenal immunohistochemical localization of HSP90 in both normal and various human diseased kidneys. We also examined the differences between the distributions of macrophages and HSP90 in cellular crescents. In the normal kidney, HSP90 was present in glomerular podocytes, Bowman's epithelia and epithelial cells from the distal tubules to the collecting duct. In diseased kidneys HSP90 was markedly expressed in the cytoplasm of proliferative cells within cellular crescents, but not in fibrocellular crescents. the localization of HSP90 in crescents did not coincide with that of macrophages. These results demonstrated that HSP90 is induced in the cytoplasm of cellular crescents. Heat‐shock protein 90 may be expressed partly in response to some factors produced by macrophages.
Value of pathological grading in prediction of renal survival in IgA nephropathy
Authors: YAGAME Mitsunori , SUZUKI Daisuke , JINDE Kiichiro , SAOTOME Noboru , MURAKAMI Rika , ASAKURA Kumiko , NAKASHIMA Risin , KASHEM Abul , YANO Naohiro , ENDOH Masayuki , NOMOTO Yasuo , SAKAI Hideto , TOMINO Yasuhiko
Published: April 2007

Summary:In order to clarify the most reliable risk factor to predict renal outcome, 206 patients with IgA nephropathy were studied for mean period of 9.2 years. the histopathological changes of this disease using light microscopy were divided into four grades (grade 1–4). These grades included glomerular, interstitial and vascular lesions. the cumulative rate of kidney survival progressing to end stage renal failure (ESRF) in all patients was 94% at 5 years, 87% at 10 years and 80% at 15 years after renal biopsy. None of the patients in grade 1 reached ESRF. the cumulative rate of kidney survival in grade 2 was 99% at 5 years, 98% at 10 years and 89% at 15 years after renal biopsy. In grade 3, it was 94% at 5 years, 79% at 10 years and 75% at 15 years. In grade 4 it was 53% at 5 years, 33% at 10 years and 22% at 15 years after renal biopsy. Forward stepwise multivariate regression analysis revealed that, in addition to the histopathological findings, three more risk factors were found to influence actuarial renal survival rate. These factors were: (i) the levels of serum creatinine; (ii) the level of serum albumin; and (iii) the amount of proteinuria at the time of renal biopsy. In parallel studies, forward stepwise multivariate regression analysis isolated three risk factors that influenced the progression of the reciprocal of serum creatinine. These factors were: (i) the levels of total protein; (ii) the degree of our pathological grading; and (iii) the amount of proteinuria. It was concluded that our pathological grading was useful as a prognostic parameter because of its simplicity and availability in routine clinical activities.
The expression of mRNA for tumour necrosis factor‐α increases in the obstructed kidney of rats soon after unilateral ureteral ligation
Authors: KANETO Hiroyuki , MORRISSEY Jeremiah J , McCRACKEN Ruth , ISHIDOYA Shigeto , REYES Alvaro A , KLAHR Saulo
Published: April 2007

Summary: Cytokines, including transforming growth factor (TGF)‐β1, contribute to the tubulointerstitial fibrosis of ureteral obstruction. Tumour necrosis factor (TNF)‐α, a proinflammatory cytokine produced by multiple cells including macrophages and resident renal cells, has a role in inflammatory cell recruitment in glomerular injury. We measured TNF‐α mRNA in the renal cortex of rats at different times after the onset of unilateral ureteral obstruction (UUO) and determined whether angiotensin II (AngII) inhibition or total body irradiation affects the mRNA levels of TNF‐α. Rats were killed at 1, 2, 4, 24, 72 and 120h after UUO. Levels of TNF‐α mRNA increased significantly in the obstructed kidney at 1h (X 2), 2h (X 2.7), 4h (X 3.6), 24h (X 2.7), 72h (X 1.8) and 120h (X 2.8) after ureteral ligation when compared to the contralateral kidney of the same animals or to control (normal) kidneys. Tumour necrosis factor‐α mRNA increased in renal cortical tubules but not in glomeruli. Treatment with enalapril, an angiotensin‐converting enzyme (ACE) inhibitor, before and after UUO decreased TNF‐α mRNA levels in the obstructed kidney by about 40% at 4h after the onset of UUO, but at 120h there was no difference in TNF‐α levels in the obstructed kidney of treated and untreated animals. Total body irradiation, which depletes macrophages in the obstructed kidney, did not prevent the upregulation of TNF‐α mRNA expression at 4 h after UUO. Thus, TNF‐α may have a role in initiating tubulointerstitial injury in the obstructed kidney. Leucocytes infiltrating the renal interstitium of the obstructed kidney do not appear to contribute to the increased mRNA expression of TNF‐α. Angiotensin II may contribute, at least in part, to the early increased expression of TNF‐α mRNA in the obstructed kidney.
Relationship between obstruction of arteriovenous fistula and plasma level of endothelin‐1 in long‐term haemodialysis patients
Authors: ONO Takahiko , NAGAI Hiroyuki , KANATSU Kazuro , KUDOH Tetsuhiro , ONOE Chika , UTSUNOMIYA Kazumasa , HARA Akira , MATSUOKA Satoru , MATSUSHIMA Hiroyuki , MUSO Eri , SASAYAMA Shigetake
Published: April 2007

Summary: The relationship between the patency status of the autogenous arteriovenous (A‐V) fistula and the plasma level of endothelin‐1 (ET‐1) was studied in 41 patients who had been receiving routine longterm haemodialysis for more than 10 years. the ET‐1 level in the haemodialysis patients (mean ± s.d.=2.1 ± 0.9 pg/mL) was significantly elevated compared with that in healthy controls (n=16; 1.1 ± 0.4 pg/mL; P < 0.01). the patients were classified into two groups according to whether the original A‐V fistula had remained patent for more than 10 years or had been repaired due to frequent (more than twice) obstruction. Among all 41 patients, 21 were receiving recombinant human erythropoietin (rHuEpo) intravenously (i.v.). In the rHuEpo‐treated group, the plasma ET‐1 (n=21; 2.4 ± 0.8 pg/mL) was significantly elevated than that in the rHuEpo‐untreated group (n=20; 1.9 ± 0.9 pg/mL; P<0.05). After exclusion of the 21 rHuEpo‐treated patients, the ET‐1 level in the repaired fistula group (n=11; 2.3 ± 0.9 pg/mL) was significantly higher than that in the patent original fistula group (n=9; 1.3 ± 0.7 pg/mL; P<0.02). Based on these results, we conclude that ET‐1 shows a close relation to venous stenosis of the A‐V fistula which may be due to its vasoconstrictive and smooth muscle cell‐proliferating effects.
Extracellular matrix, growth factors and their interactions in the pathogenesis of diabetic kidney disease
Authors: GILBERT Richard E , COOPER Mark E , JERUMS George
Published: April 2007

Summary: The accumulation of extracellular matrix (ECM) within the glomerulus is the ultrastructural hallmark of diabetic nephropathy and is directly linked to the declining renal function. the pathogenesis of these ECM changes in diabetes is not well understood but is likely to involve interaction between cells, growth factors, structural proteins and cell receptors for these molecules. Recent advances in cellular and molecular biology have highlighted the complex nature of the molecular interactions which may lead to glomerulosclerosis in diabetes.