bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of bcl‐2 protein and transcription of the Epstein‐Barr virus bcl‐2 homologue BHRF‐1 in Hodgkin's disease: implications for different pathogenic mechanisms
Authors: JIWA N.M. , OUDEJANS J.J. , BAI M.C. , BRULE A.J.C. VAN DEN , HORSTMAN A. , VOS W. , VALK P. VAN DER , KLUIN PH.M. , WALBOOMERS J.M.M. , MEIJER C.J.L.M.
Published: April 2007

Epstein‐Barr virus (EBV) is frequently found in Hodgkin and Reed‐Sternberg cells in Hodgkin's disease. Epstein‐Barr virus has transforming properties in vitro and might be involved in the pathogenesis of certain types of Hodgkin's disease. One of the possible mechanisms is the upregulation of the human proto‐oncogene bcl‐2 by the latent membrane protein 1 of EBV in vitro. Another possibility might be the expression of the viral ‘bcl‐2 homologue’, BHRF‐1. In the present study of 64 cases of Hodgkin's disease we investigated the expression of bcl‐2 at the protein level in relation to the presence of EBV. Moreover, in 10 EBV positive cases we investigated, the expression of the bcl‐2 homologue, BHRF‐1, by reverse‐transcriptase PCR. bcl‐2 was detected in 14 of 22 (64%) EBV positive and in 37 of 42 (88%) EBV negative cases. In 17 of 22 (77%) EBV positive cases Reed‐Sternberg cells were negative (n = 8) or expressed the bcl‐2 protein in a very low percentage (< 5%) of cells (n = 9), whereas in 20 of 42 (43%) of the EBV negative cases the majority (> 50%) of the neoplastic cells were bcl‐2 positive. Using the reverse‐transcriptase PCR with primers amplifying transcripts of BHRF‐1 we were able to detect BHRF‐1 transcripts in only one of the 10 tested cases of EBV positive Hodgkin's disease. Our data indicate that in EBV positive Hodgkin's disease growth advantage of Reed‐Sternberg cells is not obtained by upregulation of bcl‐2 or by the EBV homologue BHRF‐1.
p53 protein expression in colorectal adenomas: an immunohistochemical study using an antigen retrieval system
Authors: KARAMITOPOULOU E. , PERENTES E. , DIAMANTIS I. , VOGT U. , WEGMANN W.
Published: April 2007

The immunohistochemical expression of the p53 gene product was examined in 91 colorectal adenomas from patients without (group 1,50 cases) or with (group 2,41 cases) concurrent sporadic colorectal carcinoma, and in 15 additional cases of randomly selected carcinomas from group 2 patients. Immunohistochemical reactions were performed with the DO‐7 monoclonal and the CM1 polyclonal antibodies, following microwave irradiation of the tissues in an antigen retrieval solution, and the proportion of the immunoreactive cells was semiquantitatively assessed. p53 protein immunoreactivity was present in 46.1% (42, of 91, i.e., 20 out of 50 of group 1 and 22 out of 41 of group 2) and 33% (30 of 91, i.e. 14 out of 50 of group 1 and 16 out of 41 of group 2) of the adenomas using DO‐7 and CM1 antibody, respectively. High p53 expression (i.e. immunolabelling of more than 30% of the tumour cell nuclei) was found in 13.2% of the adenomas (12 of 91, i.e. three out of 50 of group 1 and nine out of 41 of group 2; P= 0.025 using the X2 test) using the DO‐7 antibody, and in 6.6% of the cases (six of 91, i.e. two out of 50 of group 1 and four out of 41 of group 2) using the CM1 antibody. In carcinomas, 80% of the cases (i.e. 12 of 15) were found to express p53 protein with both antibodies. p53 immunoreactivity in colorectal adenomas increased with the degree of dysplasia: only five (17.8%) of the 28 adenomas with mild dysplasia were found to be DO‐7 positive, while all of them remained CM1 negative. From the 50 adenomas exhibiting moderate dysplasia, 28 (56%) were DO‐7 positive, and 22 (44%) were CM1 positive. Finally, from the 13 adenomas with severe dysplasia, nine (69.2%) and eight (61.5%) were found to be positive with the DO‐7 and the CM1 antibody, respectively. Our results indicate that an increased number of group 2 adenomas express p53 protein, when compared with group 1 adenomas, and suggest that a strong correlation exists between p53 protein expression and the degree of dysplasia in colorectal neoplasms.
Are infantile myofibromatosis, congenital fibrosarcoma and congenital haemangiopericytoma histogenetically related?
Authors: VARIEND S. , BAX N.M.A. , GORP J. VAN
Published: April 2007

Infantile myofibromatosis, congenital fibrosarcoma and congenital/infantile haemangiopericytoma are generally considered distinct entities. Overlapping microscopic features between infantile myofibromatosis and congenital fibrosarcoma, and between infantile myofibromatosis and congenital/infantile haemangiopericytoma, however, have been noted, but not formally reported. This report concerns six neonatal tumours, each exhibiting more than one of the above patterns, supporting a histogenetic relationship among these entities. Immunohistochemistry for smooth muscle actin was found to be useful in the diagnosis of congenital/infantile haemangiopericytoma, and also served to support a histogenetic relationship with the other two entities under consideration.
Assessment of cell proliferation in pathology—what next?
Authors: HALL P.A. , COATES P.J.
Published: April 2007

This brief overview outlines recent progress in our understanding of the regulation of cell population size, focusing on some important developments in cell cycle control and the recognition of the importance of growth arrest and cell death. Histopathologists, and others with an interest in tissue architecture, have much to offer to those who study the biochemical and molecular processes of proliferation, growth arrest and cell death, and these processes are unlikely to be understood simply by analysis of in vitro systems and cell lines. Such biochemical and histological information may well feed back into clinical medicine in terms of new approaches and techniques, new reagents and new paradigms. With regard to the application of measures of proliferation, growth arrest and cell death as prognostic factors or other diagnostic tools, we are sceptical. Methods for assessing cell proliferation seem unlikely to be implemented widely in practice since there is little direct evidence that they are really an improvement on conventional histological assessment, optimally employed. But, there again, we may be proved wrong! In particular, it may be that, if carefully employed, assays that integrate information about death, growth arrest and proliferation may be clinically valuable.
Angiogenesis in invasive breast carcinoma: is it associated with parameters of prognostic significance?
Authors: MILIARAS D. , KAMAS A. , KALEKOU H.
Published: April 2007

Recent experimental and clinical studies suggest that tumour‐induced angiogenesis may be an important step in the evolution of malignant tumours, and may be related to prognosis. In our study we examined 42 cases of breast carcinoma (mean age: 56.76 ± 13.5), 21 with lymph node metastases and 21 without. Angiogenesis was evaluated after immunohistochemical staining of tumour vessels, using polyclonal antibody to factor VIII related antigen (VIIIR‐Ag) and counting of the three most active areas of neovascularization. In the same manner we counted the microvessels in lymph node metastases. The mean vessel count of node‐negative cases (51.16 ± 19.32) did not differ significantly from node‐positive cases (45.66 ± 17.44). In contrast patients younger than 50 years had much higher mean vessel counts (54.04 ± 16.47) than did patients older than 70 years (38.03 ± 16.73) producing a P value of ≤0.05. No association was found between tumour size and mean vessel count, nor was there any significant difference between grade I (45.94 ± 16.54), grade II (53.13 ± 23.22) and grade III tumours (51.71 ± 20.64). When we compared the mean vessel count of primary tumours with those of node metastases, we found much lower counts in the latter (P≤0.01). The differences in our results from previous studies, probably reflect the heterogeneity which exists between different tumours in their ability to induce angiogenesis. Additionally, there is some evidence in our study that angiogenesis is possibly related to patient age and probably depends on differences in the tumour stroma.
Intracytoplasmic lumina and mucinous inclusions in ovarian carcinomas
Authors: O'DONNELL M. , AL‐NAFUSSI A.I.
Published: April 2007

Intracytoplasmic mucinous inclusions and lumina have been previously described in non‐glandular neoplasms such as urothelial carcinoma. We describe their presence in 93% of non‐mucinous ovarian carcinomas. They were found in abundance in all 25 cases (100%) of clear cell carcinoma, in 48 of 50 cases (96%) of serous carcinoma and 20 of 25 cases (80%) of endometrioid carcinoma. The degree of the differentiation of the tumour did not influence the number of inclusions or lumina observed. These results suggest that the presence of intracytoplasmic lumina and mucinous inclusions is more widespread than hitherto appreciated. Their presence in an otherwise poorly differentiated metastatic carcinoma might, at the very least, prompt one to consider the ovary as a possible primary site. In addition, an abundance of intracytoplasmic mucinous inclusions and lumina with microcyst formation, in an otherwise poorly differentiated malignant primary ovarian epithelial tumour, might suggest the possibility of a clear cell carcinoma.
A study of the association of Epstein‐Barr virus with Burkitt's lymphoma occurring in a Chinese population
Authors: CHAN J.K.C. , TSANG W.Y.W. , NG C.S. , WONG C.S.C. , LO E.S.F.
Published: April 2007

There is a strong association (approximately 95%) of endemic Burkitt's lymphoma with Epstein‐Barr virus (EBV), whereas the association is weak for the sporadic form occurring in Western countries (approximately 15%). In the Middle East, North Africa and South America, 60–80% of Burkitt's lymphomas harbour EBV. These epidemiological differences suggest that either the endemicity of EBV or socio‐economic conditions, or both, may influence the pathogenetic role of EBV in Burkitt's lymphoma. Since only meagre data are available on Asians, this study was performed to address this issue by studying cases from Hong Kong, where EBV seroconversion occurs in the first few years of life but the socio‐economic conditions approach those of Western countries. In situ hybridization for EBV encoded RNAs (EBERs) was performed on paraffin sections of 18 cases of Burkitt's lymphoma. Labelling of the neoplastic cells was detected in five cases (27.7%). In contrast, among 54 cases of B‐cell lymphomas of various subtypes studied for comparison, signals for EBER were detected in only one case each of T‐cell‐rich large B‐cell lymphoma, anaplastic large cell lymphoma and Reed‐Sternberg‐like cells occurring in B‐cell chronic lymphocytic leukaemia/small lymphocytic lymphoma. The strong labelling with oligo‐dT probe (which hybridized with the polyadenylated ends of mRNA) in all cases suggested that the negative results were genuine and not due to poor preservation of RNA in the tissues. Thus, among B‐cell neoplasms occurring in Chinese, Burkitt's lymphoma shows a statistically stronger association (P < 0.01) with EBV than with other types of B‐cell lymphoma. The available data also suggest that the socio‐economic status of the country rather than exposure to EBV at an early age is the crucial factor determining the role of EBV in the genesis of Burkitt's lymphoma.
Primary pulmonary tumours of nerve sheath origin
Authors: McCLUGGAGE W.G. , BHARUCHA H.
Published: April 2007

Primary intrapulmonary tumours of nerve sheath origin are extremely rare. We describe the clinicopathological features of four such peripheral nerve sheath tumours, two benign and two malignant. Of the benign tumours, one was a typical schwannoma and the other an ancient or degenerated schwannoma. The typical schwannoma was endobronchial in origin, diagnosis being established by small bronchoscopic biopsy. The histological diagnosis of malignant peripheral nerve sheath tumour required immunohistochemical and/or ultrastructural evidence of nerve sheath differentiation. One malignant tumour arose in a patient with Von‐Recklinghausen's disease. Both malignant tumours behaved aggressively with the development of multiple intrapulmonary metastases, despite the markedly different histological appearance of the two tumours. Flow cytometric analysis of nuclear DNA content was performed on the four tumours, all of which showed a diploid DNA profile.
Synchronous adenocarcinoma and low grade B‐cell lymphoma of mucosa associated lymphoid tissue (MALT) of the stomach
Authors: WOTHERSPOON A.C. , ISAACSON P.G.
Published: April 2007

We describe nine cases of gastric adenocarcinoma (six intestinal and three diffuse type) occurring in the stomach synchronously with primary low grade B‐cell lymphoma of mucosa associated lymphoid tissue. In four cases the two neoplasms were admixed to form collision tumours. Where collision was present between lymphoma and adenocarcinoma of intestinal type no lymphoepithelial lesions were seen involving neoplastic glands. Helicobacter pylori‐like organisms were seen in seven cases (78%) which is consistent with an aetiological role for this organism in both tumours in the stomach.
Arterial elements and perisinusoidal cells in borderline hepatocellular nodules and small hepatocellular carcinomas
Authors: TERADA T. , NAKANUMA Y.
Published: April 2007

Borderline hepatocellular nodule in the human cirrhotic liver is considered a preneoplastic lesion of hepatocellular carcinoma (HCC). However, the angiogenetic process and changes in perisinusoidal cells (fat‐storing cells or Ito cells) during the borderline nodule‐HCC sequence have not been investigated. We have investigated intraparenchymal arterial elements and perisinusoidal cells in normal livers, chronic hepatitis, borderline nodules and small HCC, using an immunohistochemical staining for α‐smooth muscle actin. In normal livers, chronic hepatitis, cirrhotic nodules and large regenerative nodules, no or few arterial elements were present in the parenchyma, and α‐smooth muscle actin‐positive perisinusoidal cells were not increased. In borderline nodules, however, there were many intranodular arterial elements, and perisinusoidal cells were significantly increased. In small HCC, there were much more arterial elements, and perisinusoidal cells were increased further. These data suggest that angiogenesis first occurs in borderline hepatocellular nodules and it gradually proceeds during the nodule to HCC sequence along with an increase in perisinusoidal cells. The demonstration of arterial elements and perisinusoidal cells may be useful for the differential diagnosis of large regenerative nodule, borderline hepatocellular nodule and small HCC.
The expression of cathepsin D, oestrogen receptor and progestogen receptor in hydatidiform mole—an immunohistochemical study
Authors: CHEUNG A.N.Y. , NGAN H.Y.S. , NG W.F. , KHOO U.S.
Published: April 2007

The expression of oestrogen and progestogen receptors, as well as Cathepsin D, an oestrogen‐induced protease, in trophoblastic cells of 12 cases of complete hydatidiform mole, 12 cases of partial mole and nine cases of spontaneous abortions, were studied in an attempt to elucidate their possible roles in the pathogenesis of the diseases. The immunohistochemical studies were performed on formalin‐fixed paraffin‐embedded tissue using the ABC immunoperoxidase method. The intensity of staining and proportion of cells stained were assessed and compared in the three categories of lesions. Immunoreactivity for Cathepsin D was noted in both the syncytio‐ and cytotrophoblastic cells in all three lesions. Statistical analysis showed consistently stronger and more extensive staining for Cathepsin D in complete moles when compared with abortions. Staining for oestrogen and progestogen receptors was found to be weak in the tissues studied. The strong expression of Cathepsin D in trophoblastic cells of all three lesions, especially in complete mole, suggests that it might be important in the control of trophoblastic cell activities and involved in the pathogenesis of hydatidiform mole. The associated weak expression of sex hormone receptors also suggests that the expression of Cathepsin D in trophoblastic cells may be controlled by modes of regulation other than sex hormones.
Cavitation of mesenteric lymph nodes: a rare complication of coeliac disease, associated with a poor outcome
Authors: HOWAT A.J. , McPHIE J.L. , SMITH D.A. , AQEL N.M. , TAYLOR A.K.M. , CAIRNS S.A. , THOMAS W.E.G. , UNDERWOOD J.C.E.
Published: April 2007

Five cases are presented, all of which showed peculiar cavitation of mesenteric lymph nodes. Clinically, three presented with abdominal symptoms, a mass or obstruction, warranting laparotomy. Two patients showed cavitating mesenteric lymph nodes at autopsy. Lymph nodes were enlarged with central, partly cystic degeneration; milky fluid exuded from the cut surface. In each case, investigation showed intestinal villous atrophy and splenic atrophy; coeliac disease was confirmed by response to gluten withdrawal. Three patients died, two from cachexia and the other from pneumonia; the other two are alive and well one year and six years after presentation. Review of the literature shows 12 previously reported cases, with a mortality of about 50%. The diagnosis is made by the histopathologist, alerting appropriate treatment. The pathogenesis is unknown.
Clinicopathologic features of antineutrophil cytoplasm autoantibody (ANCA)‐associated acute renal failure in Chinese patients
Authors: CHAN TM , CHAN KW , LAWFON JWM , LO CY , LI FK , LO WK , IP M , CHENG IKP
Published: April 2007

Summary: The clinical course and renal pathologic features of anti‐neutrophil cytoplasm auto‐antibody (ANCA)‐associated renal disease were studied among Chinese patients from a single centre. Eight ANCA positive patients with acute renal impairment were studied, four of whom required dialysis shortly after presentation. Their mean age at presentation was 61.6 ± 4.2 years. Renal histology, obtained in seven patients, showed paucummune crescentic glomerulonephritis in five patients, interstitial nephritis in two patients, and small vessel vasculitis in one patient. Pulmonary baemorrhage was the other common disease manifestation, present in four of the eight patients, necessitating ventilatory support in three patients. Neurologic, cutaneous, and gastrointestinal involvement were also observed. Seven of the eight patients tested positive for pANCA and anti‐myeloperoxidase, while cANCA was detected in one patient of the eight patients, six (75%) responded to therapy, consisting of prednisolone and cyclophosphamide in five patients, and antibacterial therapy alone in one patient, who had interstitial nephritis but no evidence of vasculitis. Two patients died from sepsis and severe debilitation one month after presentation. of the other six patients, five had significant improvement of renal function, while one became dialysis‐dependent. the levels of ANCA and C‐reactive protein remained normal, and disease reactivation was not observed during follow‐up for 32.4 ± 6.1 months. Patient and renal survival rates at one year were 75% and 62.5%, respectively. It was concluded that the clinical and pathologic features of ANCA‐associated renal disease in Chinese patients are, in general, similar to those described in Caucasians. Nevertheless, cANCA‐positivity is distinctly uncommon. the demonstration of interstitial nephritis in two of the eight patients underlines the importance of renal biopsy for correct histologic diagnosis. Early institution of aggressive immunosuppression and supportive therapies are essential for the achievement of favourable outcome in patients with vasculitis.
Calcium acetate versus calcium carbonate in chronic haemodialysis
Authors: CONNOLLY J , HARRIS DCH
Published: April 2007

Summary: The purpose of this study was to compare the efficacy of calcium acetate (CA) and calcium carbonate (CC) as phosphate binders in patients on maintenance haemodialysis. A randomized, blinded, crossover study was conducted for 24 weeks in 32 subjects who were stabilized on in‐centre haemodialysis with low calcium (1.25 mmol/L) dialysate, were using calcium carbonate as their primary phosphate binder and had a pre‐dialysis serum phosphate level of ± 1.85 mmol/L. Subjects were randomized to receive CA or CC for a period of 12 weeks, followed by the other treatment for 12 weeks; Mylanta II was added as required to achieve adequate phosphate control. There were no differences in mean serum calcium or phosphate during treatment with CA and CC, and serum parathyroid level was unchanged with both. There were four episodes of hypercalcaemia (serum Ca2+ > 2.70 mmol/L) while on CA compared with 11 on CC (P= NS), and seven episodes of hyperphosphataemia (serum P1± 2.00 mmol/L) on CA compared with 21 on CC (P= 0.02). Signfficantly more Mylanta II was prescribed with CC than with CA after 8 or more weeks (P<0.05). the dose of elemental Ca2+ ingested with CC was twice that with CA. Calcium acetate was less well tolerated than CC, and five patients withdrew from the trial because of side‐effects with CA, and one with CC. In conclusion, among haemodialysis patients who can tolerate it, CA is a superior phosphate binder to CC.
Coronary angiography prior to renal transplantation
Authors: PIDGEON Grant B , LYNN Kelvin L , BAILEY Ross R , ROBSON Richard A , IKRAM Hamid
Published: April 2007

Summary: A retrospective analysis of coronary angiography in 89 patients (57 male, 32 female) on regular dialysis treatment, prior to their acceptance onto the cadaveric renal transplant waiting list, was performed. Patients studied included those older than 40 years and those symptomatic of coronary artery disease (CAD) or diabetics. Thirty patients (34%) had significant CAD: 18 one‐vessel, 8 two‐vessel, 3 three‐vessel and 1 four‐vessel disease. Significant predictors of CAD were a history of cardiac ischaemic symptoms, a diagnosis of diabetes mellitus, and a family history of CAD. There was no difference in survival between those with and those without CAD. Total mortality, and that due to myocardial infarction, was similar in patients with one‐ and two‐vessel disease and those without CAD, but increased in those with three‐ or four‐vessel disease (P<0.001). Thirteen patients (11 with CAD) were excluded from the transplant waiting list, and their survival was significantly worse (P<0.001). Restriction of coronary angiography to patients who were either symptomatic or diabetic would have resulted in 63% fewer angiograms without altering acceptance onto the transplantation waiting list for any patient.
Design of human trials in progressive renal failure
Authors: BECKER Gavin J
Published: April 2007

Summary: Future studies aimed at testing therapies to prevent progression of renal failure have much to learn from the past successful and unsuccessful attempts. Given the insensitivity of all other methods, the proper index of renal function for study of progression of renal failure should be radioisotope glomerular filtration marker clearance. Randomized prospective controlled studies are required, and statistical analysis should be designed to allow consideration for patient drop out and covariants.

Since compensatory mechanisms come into place as soon as there is any nephron damage, more attention should be paid to studying the progression of renal failure from a normal glomerular filtration rate (GFR) until there is an elevated plasma creatinine level. This suggestion is supported by four under‐lying concepts: (i) overall GFR does not fall until about 23% of nephrons are destroyed; (ii) if progression is multifactorial, the later in the progress the more likely that more factors are present to confound issues; (iii) this may allow study of greater patient numbers, since patients who have had renal biopsy or ultrasound diagnosis can be entered before the plasma creatinine is abnormal; (iv) in early stages of disease, issues of concurrent treatment may be less difficult (e.g. diet, phosphate control, hypertension).

With diabetes, prognosis and progression has been related to proteinuria. In non‐diabetic disease proteinuria has been related to progression, but the effect of alleviation of proteinuria on prognosis has not been intensively studied. There is a need to study the relationships between proteinuria and progression, particularly in early renal disease.

At present most therapies are based upon observations in the partially ablated rat model. Other animal models should be developed, and the details of early mechanisms in the rat further clarified. Since we believe progression is likely to be multifactorial in pathogenesis, combination therapies may be required to optimally reduce progression.
Discrepant effects of vasoconstrictors on the growth of early passaged cultured rat mesangial cells
Authors: ARAKAWA Toshio , OKUDA Toshihiro , INISHI Yoji , SEKITA Ken‐ichi , KASUGA Masato , KUROKAWA Kiyoshi
Published: April 2007

Summary: Mesangial cell growth stimulation by endothelin (ET) and arginine vasopressin (AVP) has been reported, but only in studies using late (3 times) pasaged cells. In the present study, we examined the effects of ET, AVP and platelet activating factor (PAF) on the proliferation of early (<3 times) passaged cultured rat mesangial cells which maintained their original characteristics. Cell growth was estimated by [3H]‐thymidine incorporation into DNA and by counting cell nuclei. After 48 h preincubation in minimal essential medium containing 0.5% fetal calf serum, ET‐1 (1‐100 nmol/L), AVP (100 pmol/L‐1 μmol/L) or PAF (1–100 nmol/L) was added to the incubation medium. In contrast to studies using late passaged cells, ET‐1 attenuated and AVP did not increase thymidine uptake (ET‐1: 18.4% inhibition at 10 nmol/L) or cell counts in early passaged cells, while the growth stimulatory effects of these agents were reproduced in late passaged cells. Platelet activating factor showed definite stimulation of cell growth in both early and late passaged cells in a dose‐dependent manner. These data strongly suggest that ET‐1 attenuates, and AVP does not stimulate, the cell growth of original mesangial cells. the PAF‐induced cell growth seems to be the constant feature of mesangial cells in vivo.
Confocal laser scanning microscopy in nephrology
Authors: GROSS Janet , BECKER Gavin
Published: April 2007

Summary: Confocal laser scanning microscopy (CLSM) has potential applications in the fields of embryology, anatomy, physiology and pathology of the kidney. This review focuses upon the principles of confocal microscopy and the ways in which this new technology may affect nephrological diagnostic pathology.
Renal ATPase‐associated disorders
Authors: EIAM‐ONG Somchai , TUNGSANGA Kriang , TOSUKHOWONG Piyaratana , SITPRIJA Visith
Published: April 2007

Summary: Three membrane bound ion translocating ATPase pumps, Na‐K‐ATPase, H‐ATPase and H‐K‐ATPase play important roles in most renal transports along the whole nephron. Proximal tubule transport, including most bicarbonate reabsorption, depends upon the generation and maintenance of a low intracellular sodium concentration created by the basolateral membrane Na‐K‐ATPase pump. Some proximal tubule bicarbonate reabsorption, however, is mediated by a luminal H‐ATPase pump. Transport in the loop of Henle also is dependent on the energy provided by Na‐K‐ATPase pump. In the distal nephron, luminal H‐ATPase and H‐K‐ATPase are responsible for all proton excretion. Accumulating data, as described in this article, have shown that alteration in these ATPase activities can cause various acid‐base disorders including proximal and distal renal tubular acidosis and Bartter's syndrome.
Mechanism of the decreased eicosanoid production in vitro in response to angiotensin II in glomeruli of rats with bilateral ureteral obstruction
Authors: YANAGISAWA Hiroyuki , KURIHARA Nobutaka , KLAHR Saulo , MORRISSEY Jerry , WADA Osamu
Published: April 2007

Summary: Glomeruli isolated from rats with bilateral ureteral obstruction (BUO) of 24 h duration synthesized significantly greater amounts of prostaglandin (PG)E2, 6‐keto PGF1a, thromboxane (Tx)B2 and leukotriene (LT)B4 than glomeruli isolated from sham‐operated control (SOC) rats. Glomeruli isolated from SOC rats produced increased amounts of these four eicosanoids compared to basal conditions when 100 nmol/L angiotensin II (AII) was added in vitro to the preparations. However, no significant increases in glomerular eicosanoid production were seen under these conditions in glomeruli of rats with BUO. to examine the mechanims underlying imparied eicosanoid production in glomeruli of rats with BUO exposed to AII in vitro, we measured the activities of phosphatidylethanolamine (PE)‐specific phospholipase A2 (PLA2), 5‐lipoxygenase and the cyclo‐oxygenase pathway enzymes including cyclo‐oxygenase, PGE2 isomerase and PGI2 and Tx synthases under basal conditions and after addition of 100 nmol/L AII in vitro in glomeruli isolated from SOC rats and rats with BUO of 24 h duration. the basal activities of all of these enzymes were significantly greater in glomeruli of rats with BUO compared to SOC rats. In glomeruli of SOC rats, the activities of these enzymes were markedly increased when exposed to 100 nmol/L AII in vitro compared to basal conditions. By contrast, no significant changes in the activities of enzymes involved in eicosanoid formation above baseline were seen in glomeruli of rats with BUO exposed to AII in vitro. the production rates of eicosanoids paralleled the activities of these enzymes under basal and AII‐stimulated conditions in glomeruli obtained from SOC rats and rats with BUO. Thus, the lack of increased levels of PGE2, 6‐keto PGF1a, TxB2 and LTB4, when glomeruli of rats with BUO of 24 h duration are exposed to 100 nmol/L AII in vitro, maybe due mainly to either the action of PE‐specific PLA2 or the combined action of PE‐specific PLA2, cyclo‐oxygenase pathway enzymes and 5‐lipoxygenase set at, or near, maximum levels as a consequence of BUO.
Atrial natriuretic peptide and verapamil can prevent gentamicin induced acute renal failure in the rat
Authors: SCHRAMM Lothar , ZIMMERMANN Josef , LOPAU Kai , LING Hong , HARLOS Joachim , HEIDBREDER Ekkehart
Published: April 2007

Summary: Calcium channel blockers are able to improve renal function in acute renal failure (ARF) and natriuretic peptides can also exert beneficial effects. At present it is unknown whether administration of atrial natriuretic peptide (ANP) and a calcium channel blocker given before a toxic lesion can prevent gentamicin induced ARF. the mechanisms of action of natriuretic peptides and calcium channel blockers are different and, as yet, it has not been clarified if combined administration can augment the effects on renal function. After a basal period we investigated the effects of verapamil (VER, 0.66 mg/kg), ANP, (30 μg/kg) and a combination of both (identical doses as described individually). the drugs were given intravenously for a period of 40 min (infusion period) before gentamicin (15 mg/kg, i.v.) was administered for induction of ARF. Basal values for glomerular filtration rate (GFR, mL/min) were around 1.8 with no differences between the groups. At the end of the infusion period (before application of gentamicin) GFR was significantly elevated with VER + ANP (3.13 ± 0.51), ANP (2.70 ± 0.59) and VER (2.34 ± 0.47) compared to controls (saline, 1.7 ± 0.48). After application of gentamicin GFR significantly dropped in the control group (0.77 ± 0.21, 0.75 ± 0.19, respectively), indicating development of ARF. In contrast with VER + ANP, ANP and VER GFR could be maintained for 30 min (2.47 ± 0.39, 2.28 ± 0.33, 2.22 ± 0.43, respectively) and 130 min (2.11 ± 0.32, 1.86 ± 0.29, 2.11 ± 0.28, respectively) after gentamicin. Moreover ANP and VER revealed natriuretic activity and, due to their vasorelaxing potency, also influenced arterial blood pressure. We conclude that both VER and ANP are able to prevent early gentamicin induced ARF when given before the toxic lesion. Both drugs induce hyperfiltration while infused, in particular when administered in combination.
Calcium acetate versus calcium carbonate: Phosphate absorption studies in chronic renal failure
Authors: JEGADEESAN L , RAMAKRISHNA BS , JOHN George T , JACOB CK , SHASTRY JCM
Published: April 2007

Summary: The aim of this study was to compare the alimentary phosphate‐binding capacity of calcium acetate to calcium carbonate in stable chronic renal failure patients who were not on haemodialysis. Intestinal absorption of phosphate and calcium was measured on three occasions in five patients with chronic renal failure who were not on maintenance haemodialysis. During each test period they received either no drug, calcium carbonate or calcium acetate (both containing 1g elemental calcium) in a randomized manner, along with a standardized meal. Intestinal contents were recovered after 10h by whole gut lavage, and phosphorus and calcium measured in meal and intestinal contents. Faecal excretion of ingested phosphorus increased from 13.85% in the absence of drug to 29.91% after calcium carbonate administration. Phosphorus excretion was significantly higher after calcium acetate (43.92%) compared to calcium carbonate (P<0.05). Less calcium was absorbed from calcium acetate than from equimolar amounts of calcium caronate (P<0.05). In patients with stable renal failure, calcium acetate is a better alimentary phosphate binder than calcium carbonate and binds more phosphorus for each mol of calcium absorbed.
Elevated urinary neopterin: A clue of activated macrophage and cellular immune response in the pathogenesis of idiopathic nephrotic syndrome
Authors: SUMETHKUL Vasant , NEILD Guy , LEOHIRUN Lakana , CHALERMSANYAKORN Panas
Published: April 2007

Summary: A study of cell mediated immunity (CMI) activation in patients with idiopathic nephrotic syndrome (INS) in the tropics was undertaken. Cell mediated immunity activation was investigated by measuring urinary neopterin excretion. All 31 patients with idiopathic nephrotic syndrome due to either minimal change nephrotic syndrome (MCNS), and focal and segmental glomerulosclerosis (FSGS) had significant elevation of neopterin excretion (mean values 451, 544 μmol neopterin/mol creatinine) when compared with 222 normal subjects (mean value 130, P < 0.001). However, in 25 patients with non‐nephrotic IgA nephropathy and eight nephrotic membranous nephropathy the urinary neopterin was not raised (mean value 131 and 129). A further 10 patients with MCNS were restudied when in complete remission and their urinary neopterin was found to have decreased significantly (mean value 186); however, this level was still above the normal range. Our study suggests that CMI and macrophage activation takes place in the pathogenesis of idiopathic nephrosis.
The existence and significance of hepatitis B virus DNA in glomerulonephritis
Authors: ZHANG Yue‐e , MA Xeiling , FANG Lijun , LIN Shanyan , WU Zhaolong , GU Jianren
Published: April 2007

Summary: In order to investigate the role of hepatitis B virus (HBV) in the pathogenesis of glomerulonephritis 50 cases of glomerulonephritis with HBV antigenaemia and/or hepatitis B antigen (HBAg) detected by immunohistochemistry in renal tissue were collected. the distribution and localization of HBV DNA were observed by using in situ hybridization. In addition, Southern blot analysis was performed on 23 of the 50 cases in order to reveal the state of renal HBV DNA. Thirty‐six cases (72%) were found to be HBV DNA positive by in situ hybridization, which localized in the nucleus of tubular cells. In 26 cases HBV DNA was detectable in the nucleus of glomerular mesangial and epithelial cells as well as the mesangial matrix. Seventeen of the 23 cases were proved to be HBV DNA positive in Southern blot analysis (82%). Three of these cases were identified with non‐replicating free HBV DNA, while 14 cases were the integrated form. the results of this study showed that the renal tissue was infected with HBV; however, it was considered that it may be possible that the HBAg deposited on glomeruli was not only from circulation but also from the HBV infected glomerular cells although the evidence of this is not conclusive. In addition to the humoral immune injury mediated by HBAg‐hepatitis B antibody (HBAb) immune complexes the cellular immune injury mediated by target antigen (hepatitis B core antigen; HBcAg) might be also involved in the pathogenesis of HBV glomerulonephritis (GN) associated GN.
Lymphoproliferative disorder post renal transplantation: Recent experience at a single centre
Authors: PEDAGOGOS Eugenia , DOWLING John , ROCKMAN Steven , NICHOLLS Kathy , FRASER Ian , WALKER Rowan
Published: April 2007

Summary: Post‐transplant lymphoproliferative disorder was diagnosed in six renal transplant recipients at the Royal Melbourne Hospital over a 5 year period to December 1994. This constituted a detection rate of 2.2%. All patients were treated with cyclosporine, azathioprine, prednisolone and orthoclone (OKT3). the median time of onset was 2 months (range 0.3 months‐3 years) after transplant. Two patients who ultimately died presented with the diffuse form of the disease where immunoblasts massively infiltrated all organs. These tumours were monoclonal B cell lymphomas and Epstein‐Barr virus (EBV) reactivation could be demonstrated. One patient developed a polyclonal B cell tumour with primary EBV infection and the remaining 3 patients tresented with T cell polyclonal proliferations and were EBV negative. No cytomegalovirus (CMV) infections, primary or reactionary were observed. Therapy in all cases consisted of reducing or ceasing immunosuppressive treatment and in three patients ganciclovir was used. Four polyclonal tumours responded to the treatment measures.
Glomerular capillary wall permeability to albumin and horseradish peroxidase
Authors: OSICKA Tanya M , PRATT Lynette M , COMPER Wayne D
Published: April 2007

Summary: Tritium labelled albumin present in urine fractions from in vivo rat filtration studies and isolated perfused rat kidneys (IPK) has been shown by gel chromatographic analysis to be severely degraded (approximately 90%) to small peptides. the in vivo degradation of rat serum albumin and bovine serum albumin has been shown to be similar. the degradation has a marked influence on the fractional clearance analysis. the fractional clearance for albumin in the isolated perfused kidney as determined by Lowry assay was 0.00180 ± 0.0007, 0.0060 ± 0.0033 by Biuret assay and 0.0075 ± 0.0039 as measured by total radioactivity in the urine. Specific analysis of intact albumin by gel chromatography gave a fractional clearance of 0.00039 ± 0.00016, which is comparable to in vivo values. Degradation of albumin in the urine from IPK experiments was inhibited by 42% by including 150 mmol/L lysine, an inhibitor of tubular cell uptake, in the perfusate. Inhibition of degradation of anionic horseradish peroxidase was also observed. These studies demonstrate that albumin is degraded during renal passage probably by tubular cells. In a series of isolated perfused kidney systems using different inhibitors of protein tubular uptake, namely lysine, ammonium chloride, chloroquine and cytochalasin B, we estimate the glomerular sieving coefficient of albumin to be approximately 0.074 as determined using [3H]‐albumin. This glomerular sieving coefficient is considerably higher than originally thought, yet it is in accord with the size selectivity characteristics of the glomerular capillary wall as determined by transport probes calibrated for hydrodynamic size by gel exclusion chromatography. the tubular inhibitors also destroyed charge selectivity of the anionic and neutral forms of albumin and horseradish peroxidase. the tubular inhibitors were characterized in terms of their effect on tubular lysozyme uptake and glomerular size selectivity as determined using polydisperse dextran fractions. By accounting for the destination of all the tritium labelled albumin in the urine, perfusate, whole kidney and isolated glomeruli we conclude that a major rapid transtubular cell pathway must exist that directs albumin from the tubular lumen to either the renal lymphatics or peritubular capillaries or both. This pathway appears to be an overload pathway because since the albumin concentration in the perfusate was lowered from 50 mg/mL to 2.0 mg/mL it was not active. the pathway is also inactive for other proteins, such as horseradish peroxidase, that are at relatively low concentration.
Vitamin D metabolites and growth hormone therapy in uraemic rats: the short‐term effect on growth failure and hyperparathyroidism
Authors: HISANO Satosi , LANGMAN Craig B , LATTA Kay , KRIEG Richard J , CHAN James CM
Published: April 2007

Summary: The aim of our study was to evaluate the effect of 1,25 dihydroxyvitamin D3 (D), 22‐oxacalcitriol (O) or recombinant human growth hormone (GH) on growth failure and hyperparathyroidism in 5/6 nephrectomized uraemic (Ur) rats. Seven groups of rats were studied: (i) sham controls (SC; n=6); (ii) Ur controls (UrC;n=8); (iii) Ur treated either with D (UrD; n=7); (iv) O (UrO, n=8); (v) GH (UrGH; n=7); (vi) D+GH (UrDGH; n=9); or (vii) O+GH (UrOGH; n=7). For 14 days, D and O were administered intraperitoneally daily at 30 ng/kg per day and GH subcutaneously daily at 1.3 i.u./day. Four weeks after 5/6 nephrectomy, plasma creatinine (Cr), plasma and urine calcium (Ca), plasma phosphate (P), ratio of urine Ca/urine Cr, amino‐terminal parathyroid hormone (PTH; pg/mL) and Ca/dry bone weight in the left femur (mg/g) were measured. Uraemic controls, UrD, UrO and UrDGH rats were lower in weight gain than SC rats over the study period, but linear growth was not retarded in any uraemic group. Plasma Cr was greatly increased in any Ur group as compared with SC group. Plasma Ca and P concentrations did not differ among each group. the ratio of urine Ca/urine Cr in UrD and UrDGH groups was higher than SC, UrCand UrGH groups. the use of Dor D+GH suppressed PTH, returning the level in these rats to the normal level of the SC rats, while the PTH concentrations in the UrO and UrOGH rats were less decreased. Bone Ca content was enhanced by D+GH and O+GH administration in comparison with UrC rats, but there was no difference in the bone Ca content between UrD and UrDGH rats, and between UrO and UrOGH rats. In conclusion, growth failure in weight was shown in uraemia, but linear growth was not retarded in any uraemic group. 1.25 dihydroxyvitamin D3 and D plus GH successfully suppressed secondary hyperparathyroidism. Further studies are needed in order to elucidate the interactions on bone between vitamin D rnctabolites and GH.
Glomerular TGF‐β1 expression in children with nephrotic syndrome
Authors: ITO Toshiyuki , TANAKA Hiroyuki , YASUI Masato , KOBAYASHI Yasushi , SEINO Yoshiki
Published: April 2007

Summary: Transforming growth factor‐β (TGF‐β) has been suggested to contribute to the onset and/or progression of glomerulonephritis. However, data of TGF‐β in connection with the pathogenesis of nephrotic syndrome are still insufficient. an immunohistochemical study on the glomerular TGF‐β1 in nephrotic syndrome was carried out in order to clarify the pathological role of this substance. Ten cases of nephrotic syndrome were subdivided histologically into two groups: (i) six cases of minor glomerular abnormality (group M); and (ii) four cases of focal glomerular sclerosis (group F). Two cases with normal glomeruli, one case of normal portion of adult renal cell carcinoma, one case of normal portion of Wilm's tumour were also studied as controls. Four cases of asymptomatic haematuria (group H) and four cases of chronic non‐IgA glomerulonephritis syndrome (group C) were chosen compared to the nephrotic syndrome. Staining was evaluated semiquantitatively by light microscopy and by measuring the staining ratio compared to the glomerular area on an image analyzer. Both methods showed significantly larger staining in the glomeruli of group F, compared to group M. We concluded that TGF‐β1 plays an important role in the progression of nephrotic syndrome.
Acute infusion of amphotericin B: Proximal tubular effects
Authors: POLLOCK Carol A , DYNE Marlen , FIELD Michael J , MOORE Noriah SALIPAN , REDDY Sri , COCKAYNE David , GYÖRY ÁKos Z
Published: April 2007

Summary: Electron microprobe analysis (EMPX) was employed to determine the alterations in intracellular electrolyte concentrations in proximal tubular cells resulting from acute treatment with amphotericin B. Concurrent clearance data confirmed a drop in glomerular filtration rate (GFR) in the rats treated with amphotericin B infusion (1 mg/kg per h) compared to control animals infused with saline (0.69 ± 0.11 vs 1.27 ± 0.08 mL/min per 100 g; P < 0.001). Measurement of intracellular electrolytes in proximal tubular cells in mmol/kg wet weight by EMPX demonstrated no difference in Na (16.2 ± 0.6 vs 17.2 ± 0.5) or K (129.7 ± 2.1 vs 131.3 ± 2.0). Intracellular Rb accumulation following acute infusion was significantly reduced in the amphotericin B treated animals (3.9 ± 0.4 vs 6.6 ± 0.4; P < 0.0001), suggestive of a reduction in basolateral Na‐K ATPase activity. These results do not support the tenet that amphotericin B causes a generalized increase in epithelial cell membrane ionic permeability, nor direct tubular toxicity in the doses and time frame studied. Rather, they suggest that a primary reduction in GFR results acutely in a load‐dependent decrease in proximal tubular Na transport.
Validation of limulus tests for endotoxin evaluation in dialysate
Authors: YAMAMOTO Chieko , KIM Sung‐Teh
Published: April 2007

Summary: To measure endotoxin (ET) levels in dialysate accurately, three commercial limulus tests (Endospecy, Seikagaku, Tokyo, Japan; Kinetic QCL, BioWhittacker, MD, USA; ET single test‐ES, Wako, Osaka, Japan) were validated in order to determine whether or not they are enhanced or inhibited by bicarbonate dialysate. Two reference standard ET, one from US Pharmacopoeia (Escherichia coli reference standard endotoxin; RSE) and the other from European Pharmacopoeia (Salmonella RSE), were adjusted with dialysate at concentrations of 0.05, 0.10 and 0.15 EU/mL for measurement by each kit. A simple linear regression line forced to the origin was generated for each kit. the validation criteria, based upon accuracy and precision analysis, includes the fact that the range of slope of the regression line of 95% confidence must fall between 0.75 and 1.25, and the correlation coefficient must be no less than 0.99 with significance (P < 0.05). No enhancement/inhibition was observed with Endospecy. Kinetic QCL showed enhancement with Salmonella RSE and no enhancement/inhibition with E. coli RSE. the ET single test‐ES kit was inhibited with both RSE. Clinical dialysate samples were also measured for ET activity by each limulus kit which revealed that Endospecy and Kinetic QCL gave almost identical values; however, the ET single test‐ES kit gave significantly lower values (41%) than the others (P < 0.05). These results suggest that either the validation test using RSE or comparative analysis with an already validated kit (Endospecy) is necessary for measuring ET levels in dialysate.