bluuebunny/crossref_metadata_2025 huggingface dataset:
Membranous Glomerulopathy Associated with Graft-versus-Host Disease following Allogeneic Stem Cell Transplantation
Authors: Lin Julie , Markowitz Glen S. , Nicolaides Maria , Hesdorffer Charles S. , Appel Gerald B. , D’Agati Vivette D. , Savage David G.
Published: April 2003

We report two cases of nephrotic syndrome presenting 18 and 20 months after allogeneic stem cell transplantation (alloSCT) with chronic myelogenous leukemia. Both patients had acute and chronic graft-versus-host disease (GVHD) and renal biopsy findings of membranous glomerulopathy (MG). A review of the literature revealed 10 additional cases of immune-complex-mediated glomerular disease following alloSCT, 8 of which were diagnostic of MG. All patients showed evidence of acute or chronic GVHD. Patients typically presented with preserved renal function (mean creatinine 1.2 mg/dl) and full nephrotic syndrome including heavy proteinuria (mean 9.2 g/24 h), edema, hypoalbuminemia (mean 2.1 g/dl) and hypercholesterolemia (mean 472 mg/dl). Most patients showed stabilization of renal function and significant decreases in proteinuria when treated with steroids and/or cyclosporine. The close temporal association as well as evidence from murine models of GVHD support a pathogenetic association between GVHD and the development of MG.
Retrospective Study of Children with Acute Pyelonephritis
Authors: Ghiro L. , Cracco A.T. , Sartor M. , Comacchio S. , Zacchello G. , Dall’Amico R.
Published: April 2003

The purpose of the study was to investigate the management of pyelonephritis in a large Italian pediatric population. A total of 1,333 patients (36% male) were considered. Escherichia coli was the most frequently isolated agent (89.9%), followed by Proteus mirabilis (3.6%) and Klebsiella oxytoca (2.1%). 27% of microorganisms were resistant to amoxicillin, 4% to amoxicillin/clavulanic acid, 11% to trimethoprim-sulfamethoxazole, 2.4% to gentamicin and less than 2% to ceftazidime. Despite this resistance pattern showing that oral antibiotics, such as amoxicillin/clavulanic acid, are effective in vitro as well as parenteral antimicrobials, a parenteral antibiotic was given initially to 756 (57.2%) children. A prophylactic regimen was started in 922 patients with a rate of reinfection during prophylaxis of 9.5%; a higher rate of reinfection was observed in patients with reflux (25%) compared to children without reflux (3%) (p < 0.0001). Vesicoureteral reflux was demonstrated in 30% of patients. The number of renal abnormalities detected by DMSA in patients with and without reflux was significantly different (p < 0.001). CRP was higher in patients with scars (p < 0.02). In conclusion, pyelonephritis represents a common disease with about 2,500 days of hospitalization per year in the Veneto Region where there is a pediatric population of about 800,000 under 15 years of age. The results of antimicrobial in vitro tests indicate that amoxillicin/clavulanic acid could represent the antibiotic of choice. The high frequency of malformations, observed even in children between 6 and 12 years of age, may suggest the need of an imaging study including DMSA scan and VCUG in all age groups.
Methylenetetrahydrofolate Reductase Gene Polymorphism, Hyperhomocysteinemia, and Cardiovascular Diseases in Chronic Hemodialysis Patients
Authors: Morimoto Kan , Haneda Takashi , Okamoto Kiyotaka , Ishida Hironori , Kikuchi Kenjiro
Published: April 2003

Cardiovascular disease (CVD) is the principle cause of death in patients with end-stage renal disease. Some gene polymorphisms and hyperhomocysteinemia have been implicated in the pathogenesis of CVD. The aim of this study was to assess the relationships between angiotensin-converting enzyme genotype, endothelial nitric oxide synthase genotype, and methylenetetrahydrofolate reductase (MTHFR) genotype and CVD in patients on hemodialysis and to clarify the determinants of plasma homocysteine level. One hundred and sixty-eight patients on hemodialysis (87 males and 81 females, mean age 60.7 ± 13.1 years) were included. A history of CVD was present in 25% of the patients. There was a significant difference in the distributions of MTHFR non-VV genotype and MTHFR VV genotype between patients with a CVD history and patients without a CVD history, but no difference in the distributions of angiotensin-converting enzyme genotypes and endothelial nitric oxide synthase genotypes. The plasma homocysteine concentration was significantly higher in patients with MTHFR VV genotype than in patients with MTHFR non-VV genotype. The plasma homocysteine concentration was negatively correlated with plasma vitamin B12 concentration and plasma folate concentration. On stepwise multiple-regression analysis for the predictors of plasma homocysteine concentration, MTHFR VV genotype and gender were significant. In conclusion, MTHFR polymorphism may be a risk factor for CVD in patients on hemodialysis, and MTHFR VV genotype and gender may be strong determinants of the plasma homocysteine level.
Hyperhexosemia Induced Functional and Structural Changes in the Kidneys: Role of Endothelins
Authors: Chen S. , Evans T. , Deng D. , Cukiernik M. , Chakrabarti S.
Published: April 2003

Background/Aims: Glomerular basement membrane (GBM) thickening and mesangial matrix expansion are characteristic features of diabetic nephropathy. The present study investigates the role of endothelins (ETs) in the pathogenesis of such changes in diabetic nephropathy. Methods: Diabetic (streptozotocin-induced, 65 mg/kg), galactose-fed (30%) and control animals were followed up for 1 and 6 months. Animal groups also included diabetic and galactose fed animals on dual ETA/ETB receptor antagonist bosentan (100 mg/kg). A semi-quantitative reverse transcription polymerase chain reaction method was used to quantify mRNA expression of ET-1, ET-3, ETA, ETB, fibronectin and collagen α2(IV). Histological analyses of the kidneys and ET-1, ET-3 and fibronectin immunohistochemistry were performed. Morphometric assessment of the GBM after 6 months was performed. Results: Diabetes increased mRNA expression of ET-1, ET-3, ETA, ETB, fibronectin and collagen α2(IV) after one and six months. In contrast, although increased ETA and ETB mRNAs were present following galactose feeding both at 1 and 6 months, ET-1, ET-3, fibronectin and collagen α2(IV)mRNAs were increased after 6 months. Both diabetes and galactose feeding caused increased GBM thickening. Furthermore, diabetes caused an increase in mesangial matrix production. Bosentan prevented increased fibronectin and collagen α2(IV) mRNA expression, increased mesangial matrix deposition and GBM thickening. Conclusion: This study has demonstrated that diabetes and galactose feeding induced functional and structural changes in the kidney are mediated via ETs.
A Comparative Study of Femoral Head Diameters and Sex Differentiation in Nigerians
Authors: Asala S.A. , Mbajiorgu F.E. , Papandro B.A.
Published: April 2003

The vertical and transverse diameters of the head of 504 paired human femurs (257 males and 247 females) from Maiduguri in the northeastern arid zone of Nigeria were measured. Identification points and demarking points were determined. The mean diameter of the head of the male femur was significantly greater than that of the female (p <0.001). The identification points that were derived from the vertical and transverse diameters of the head of the femur were higher in males than in females. Those that were derived from the vertical diameters of the head of the male femurs were comparable to the values from the southeastern part of Nigeria. Those that were derived from transverse diameters were lower than the corresponding values from southeastern Nigeria. By means of identification points, more male bones were identified. This was due to the fact that the mean head diameter of female femurs fell within the range of diameters that did not permit positive identification of sex. The male demarking points were also higher than the corresponding female values. Similarly, the demarking point identified the sex of a higher percentage of male femurs. The demarking point, in comparison to the identification point, identified the sex of a smaller percentage of femurs. The results showed that diameters of the femoral head as well as the identification and demarking points that are derived from them are of use in sex and regional identification.
Articular Facets of the Coracoclavicular Joint in Koreans
Authors: Cho B.P. , Kang H.S.
Published: April 2003

This study was performed to investigate the occurrence of the coracoclavicular joint in Koreans. Materials used in this study were paired clavicles and scapulae obtained from 102 adult Korean cadavers (61 males, 41 females) ranging from 18 to 97 years in age. The occurrence of the joint was identified by a definite articular facet on the conoid tubercle of the clavicle and also by one on the superomedial surface of the coracoid process of the scapula. To compare the morphometric differences between specimens with and without coracoclavicular joint, the clavicle length, scapular border length, glenoid length, coracoid height, coracoacromial (CA) arch height, coracoid slope, and acromion slope were measured on all bones examined. The coracoclavicular joint was found in 10 (9.8%) of 102 individuals examined. Among them, nine (8.8%) showed bilateral coracoclavicular joints, and a unilateral right joint was noted in one case (1.0%). No significant difference in the incidence of the joint was noted between the right and left side. The incidence of the joint in males, a frequency of 9.8%, was the same as that in females. The joint was not found in individuals under 40 years old. However, the joint was present in 9.5% of those aged 40–59 years, and in 11.4% of those aged 60 years or over. There was no significant difference between various measurements taken from specimens with and without a coracoclavicular joint. These findings suggest that the occurrence of the coracoclavicular joint is related to aging, but not to the size of the scapulae or the slopes and heights of some CA arch elements.
Glycoproteins and Their Relationship to Human Disease
Authors: Brockhausen I. , Schutzbach J. , Kuhns W.
Published: April 2003

Glycoproteins are proteins that carry N- and O-glycosidically-linked carbohydrate chains of complex structures and functions. N-glycan chains are assembled in the endoplasmic reticulum and the Golgi by a controlled sequence of glycosyltransferase and glycosidase processing reactions involving dolichol intermediates. The assembly of O-glycans occurs in the Golgi and does not involve dolichol. For most reactions, families of glycosyltransferases exist; the expression of the individual enzymes within a family is often subject to complex regulation. The biosynthesis of N- and O-glycan is controlled at the level of gene expression, mRNA, enzyme protein activity and localization, and through substrate and cofactor concentrations at the site of synthesis. This complex regulation results in many hundreds of structures, the range of which varies in different species, cell types, tissue types, states of development and differentiation. In diseased cells, the relative proportions of these structures are often characteristically different from normal, and may be useful for the assessment of the stage of the disease and for diagnosis. Knowledge of disease-specific glycoprotein structures and their functions may be used therapeutically, in immunotherapy, in blocking cell adhesion or interfering with other binding or biological processes. Recently, some of the mechanisms underlying glycoprotein alterations in disease have been elucidated. This opens the possibility of an active interference in the disease process. The functions of glycans in diseased cells will become more clear with the tools of molecular biology and transgenic animal models.
Identification of an Autocrine Signaling Pathway That Amplifies Induction of Endocardial Cushion Tissue in the Avian Heart
Authors: Ramsdell A.F. , Moreno-Rodriguez R.A. , Wienecke M.M. , Sugi Y. , Turner D.K. , Mjaatvedt C.H. , Markwald R.R.
Published: April 2003

Endocardial cushion tissue is formed by an epithelial-mesenchymal transformation of endocardial cells, a process which results from an inductive interaction between the myocardium and endocardium within the atrioventricular (AV) and outflow tract (OT) regions of the heart. We report here that a protein previously found to be required for myocardially induced transformation of endocardial cells in vitro, ES/130, is highly expressed within the AV and OT regions not only by myocardial cells, but also by the endocardium and its mesenchymal progeny. Given these findings and others, we have tested the hypothesis that endocardial cushion tissue secretes factors which autoregulate its transformation to mesenchyme. Endocardial cushion tissue was cultured and its conditioned growth medium was harvested and applied to nontransformed endocardial cells maintained in the absence of the inductive myocardium. This treatment resulted in endocardial cell invasion into three-dimensional collagen gels plus increased expression of proteins associated with endocardial cell transformation in vivo. Whereas endocardial cushion tissue was found to express ES/130 protein in vivo and in vitro, minimal detection of ES/130 in its conditioned growth medium was observed in immunoblots. Attempts to inhibit the mesenchyme-promoting activity of the conditioned medium with ES/130 antisense were unsuccessful. However, strong intracellular ES/130 expression was detected in endocardial cells, and this expression correlated with the ability of endocardial cells to transform. For example, the minority of endocardial cultures that failed to transform in response to conditioned medium treatment also failed to undergo increased expression of ES/130. These observations are interpreted to suggest that (i) endocardial cushion tissue secretes factors that promote its transformation to mesenchyme, and (ii) while endocardial cushion tissue appears to signal through secretion of factors other than or in addition to ES/130, intracellular ES/130 expression nevertheless may be a target endocardial cell response required for endocardial cell transformation.
Three-Dimensional Distribution of Intercellular Adhesion Molecule-1 on Lymphocytes in the High Endothelial Venule Analyzed by Backscatter Electron Imaging
Authors: Sasaki K. , Okouchi Y. , Rothkötter H.-J. , Pabst R.
Published: April 2003

The intercellular adhesion molecule-1 (ICAM-1) is a ligand for the β2 integrin. It is present on the vascular endothelium and plays an important role in cell to cell interaction in lymphocyte recirculation. ICAM-1 is expressed not only on the endothelium but also on other cells, especially lymphocytes adhering to the endothelium, B cells and mitogen-stimulated T cells. To define the functional role of ICAM-1 in lymphocytes, the three-dimensional distribution of ICAM-1 on the surface of lymphocytes in the rat mesenteric lymph node HEV was investigated by immunoscanning electron microscopy. ICAM-1 expression was closely associated with variations in surface structures of lymphocytes, which showed a cap-like structure, membrane ruffles and slender microvilli. ICAM-1 was preferentially localized on the cell surface including membrane ruffles (about 90% of all counted gold particles), but rarely on the microvilli (10%). The results suggest that activated lymphocytes with variations in surface structures demonstrate moderate expression and preferential localization of ICAM-1. This seems to enable a three-dimensional interaction of the microvilli of one lymphocyte with the surface membrane of another cell and might be a prerequisite for cluster formation between them, as seen in antigen presentation.
Association of Kinesin with Microtubules in Diverse Cytoskeletal Systems in the Outer Segments of Rods and Cones
Authors: Eckmiller M.S. , Toman A.
Published: April 2003

The membranous outer segments of vertebrate photoreceptors are supported by cytoskeletons consisting of microtubules and associated proteins, which occur as the ciliary axoneme in rods and cones, and as a separate cytoskeletal system at the incisures of rod outer segments. We performed an immunocytochemical study of the cytoskeleton in photoreceptors isolated from amphibian retinas and found that immunoreactivity to the heavy chain of the motor protein kinesin was closely associated with the microtubules in each of these outer segment cytoskeletal systems. In the outer segments of cones, kinesin heavy chain immunoreactivity was confined to a streak at the axoneme that extended to the outer segment tip. In the outer segments of rods, kinesin heavy chain immunoreactivity was found as both a short streak at the axoneme and a series of long parallel lines that coincided with the microtubules at rod outer segment incisures. Our findings constitute the first report of kinesin in the axoneme of cones and at the incisures of rods. Closely associated with microtubules, kinesin in photoreceptor outer segment axonemes and at rod outer segment incisures can transport materials longitudinally along the microtubules and/or connect these with each other and/or with other components. Because these cytoskeletal systems differ in fundamental ways, kinesin can play different roles in each case, e.g., kinesin at rod outer segment incisures can have structural and functional roles that are unique to rods. These findings may have clinical relevance because similar cytoskeletal systems are expected to occur in the outer segments of human photoreceptors; thus, a disturbance involving kinesin in the cytoskeletal systems at photoreceptor axonemes and/or at rod outer segment incisures could interfere with the normal structure and function of photoreceptors and contribute to human photoreceptor degenerations.
Serine / Threonine Protein Phosphatases Type 1, 2A and 2C in Vertebrate Retinae
Authors: Selke D. , Anton H. , Klumpp S.
Published: April 2003

A number of retinal proteins are phosphorylated by a variety of kinases, resulting in well-known regulatory effects. The identity and role of corresponding phosphatases is less clear. We simultaneously measured the activity of serine/ threonine protein phosphatases type 1, 2A and 2C in bovine retinae. The enzymes were classified according to substrate specificity, divalent cation requirement and the effect of phosphatase subtype-specific inhibitors. The total- and specific activity of phosphatase type 2A was prevalent. Type 2C was 10-fold less abundant. 80% of type 1 and 50% of type 2A and type 2C, respectively, were soluble. An economic purification scheme was developed. We demonstrated the presence of phosphatase isozymes 2Cα and 2Cβ in bovine rod outer segments by enzymatic analysis as well as immunological techniques. The results suggest a yet unknown role of phosphatase type 2C in phototransduction. On the other hand, the immense amount of protein phosphatases found to be soluble – therefore not associated with rod outer segment membranes – points towards participation of these enzymes in the process of visual transduction not considered thus far.
Neural Substrate for Motor Control of Feeding in Amphibians
Authors: Dicke U. , Roth G. , Matsushima T.
Published: April 2003

Descending pathways to premotor/motor centers and their cell groups of origin were studied by means of retrograde biocytin tracing experiments in the frog Discoglossus pictus and the plethodontid salamander Plethodon jordani, which differ remarkably in the structure and function of their feeding apparatus and their feeding strategy. Labeled neurons were found in 30 major cell groups located in the telencephalon, diencephalon, synencephalon, mesencephalon and rhombencephalon. The number and distribution of nuclei are very similar in both species. Furthermore, the descending pathways of these groups of neurons take the same courses inside the medulla oblongata. Axons of most nuclei descend either in the ventromedial or ventrolateral medulla oblongata, and it is concluded that the spatial arrangement of pathways is identical in the species studied. Bilateral electrical stimulation of the optic tectum of the plethodontid salamander Hydromantes italicus elicited strong discharges of short latencies in the hypoglossal nerve. In most hypoglossal motor neurons, excitatory postsynaptic potentials (EPSPs) of short latencies followed paired shocks applied at intervals as short as 3 ms, but showed temporal and spatial facilitation, suggesting that the EPSPs include mono- as well as polysynaptic components. In the ventral white matter, orthodromic single units were found that are candidates for excitatory reticular interneurons. These properties of tectal descending pathways in salamanders strongly differ from those found in toads. Differences in feeding behavior and its control by the premotor/motor networks between the species investigated do not appear to result from anatomically altered input or from a different organization of descending pathways to these premotor/motor centers, but rather from differences in local properties of reticular premotor networks as well as from different effects of neuromodulatory systems.
Evolution to Acute Myeloblastic Leukemia from Chronic Neutrophilic Leukemia with Dysplastic Features in Granulocytic Lineage
Authors: Ota Shuichi , Tanaka Junji , Kobayashi Sumiko , Tsuda Yuzo , Mori Akio , Noto Satoshi , Yamamoto Yasushi , Hashino Satoshi , Musashi Manabu , Imamura Masahiro , Asaka Masahiro
Published: April 2003

We experienced the case of an 82-year-old man with chronic neutrophilic leukemia (CNL) with dysplastic features in the granulocytic lineage which subsequently progressed to acute myeloblastic leukemia (AML) with myelofibrosis. The patient had hepatosplenomegaly, but there was no evident cause of neutrophilic leukocytosis. The cytogenetic study showed that he had a normal karyotype. Concentrations of the serum granulocyte colony-stimulating factor (G-CSF) were not detectable. Two years after the diagnosis of CNL, blastic transformation to AML occurred with myelofibrosis and significant morphological abnormalities in neutrophils. The blasts were positive for myeloperoxidase, CD33, CD34, and HLA-DR, and the presence of dysplasia within the granulocytic lineage suggested that he had an abnormality at the level of the granulocyte-committed progenitors. Heterogeneous origins of CNL might lead to various clinicopathological features in each case.
Mucosa-Associated Lymphoid Tissue Lymphoma of the Salivary Glands Occurring in Patients Affected by Sjögren’s Syndrome: Report of 6 Cases
Authors: Biasi Domenico , Caramaschi Paola , Ambrosetti Achille , Carletto Antonio , Mocella Stelio , Randon Massimo , Bambara Lisa M.
Published: April 2003

Objective: Mucosa-associated lymphoid tissue (MALT) lymphoma of the salivary glands occurring in 6 patients affected by primary Sjögren’s syndrome is reported. Methods: Clinical findings, histologic type, stage, treatment and outcome of the 6 patients have been revised. Results: In all 6 cases the lymphoma was of the MALT type. Four patients had stage IE disease, 1 patient had stage IIE disease and 1 patient had stage IV disease. The patients received different treatments resulting in all cases in prolonged remission. After 7 years of complete remission 1 patient developed a diffuse large B-cell lymphoma. Conclusion: MALT lymphoma of the salivary glands is an indolent disease. Though the best therapy of this lymphoproliferative disorder remains to be established, prolonged remission has been obtained in our cases with different therapeutic approaches. We review the literature regarding the relationship between Sjögren’s syndrome and MALT lymphomas and study the mechanisms which may be involved in the transformation from a lymphoepithelial lesion into a neoplastic disorder.
Update on Tumor Cell Procoagulant Factors
Authors: Gale Andrew J. , Gordon Stuart G.
Published: April 2003

Tumor cells produce tissue factor, cancer procoagulant, plasminogen activators and other factors that interact with the coagulation system, the fibrinolytic system and vascular or blood cells such that they can upset the normal homeostasis and balance between activation and inhibition of the coagulation and fibrinolytic systems. These activities play a role in tumor cell growth and metastasis, vascular wall function, and hemostasis. Proteases and their inhibitors are intimately involved in all aspects of the hemostatic, cell proliferation and cellular signalling systems. This review provides a brief examination of recent observations in this complex interaction of cellular and hemostatic factors.
Haemolytic Anaemia in a Patient with Anorexia nervosa
Authors: Kaiser Ulrich , Barth Nikolaus
Published: April 2003

We report on a 17-year-old female patient with severe anorexia nervosa (AN) (body mass index of 9.8 kg/m2) who developed hypophosphataemia (serum phosphate 0.4 nmol/l) and subsequent haemolytic anaemia during oral refeeding. Hypophosphataemia due to an increased phosphate uptake may lead to a reduction of erythrocyte adenosine triphosphate. This mechanism is important for the differential diagnosis of haemolytic anaemia in patients with AN. To prevent this complication, phosphate supplementation should be considered in the refeeding of severely malnourished patients.
Bone Marrow Angiogenesis and Plasma Cell Angiogenic and Invasive Potential in Patients with Active Multiple Myeloma
Authors: Vacca Angelo , Ribatti Domenico , Roccaro Aldo M. , Ria Roberto , Palermo Loredana , Dammacco Franco
Published: April 2003

Factor VIII-related antigen-positive microvessel areas were measured by both immunohistochemistry and computerized image analysis in patients with active multiple myeloma (MM), nonactive MM and monoclonal gammopathies of undetermined significance (MGUS). A 5- to 6-fold larger area was found in patients with active MM compared to the other two groups. The conditioned medium (CM) of their bone marrow plasma cells stimulated endothelial cell proliferation and chemotaxis, monocyte chemotaxis and angiogenesis in vivo [chick embryo chorioallantoic membrane (CAM) system] more strongly and frequently than the CM of patients with nonactive MM and MGUS. An immunoassay of plasma cell lysates gave significantly higher levels of fibroblast growth factor-2 (FGF-2) in patients with active MM than in the other two groups, and a neutralizing anti-FGF-2 antibody inhibited by 54–68% the biological activity exerted by the CM in vitro and in the CAM. In situ hybridization of bone marrow plasma cells and gelatin zymography of CM showed that patients with active MM express higher levels of matrix metalloproteinase-2 (MMP-2) mRNA and protein than those with nonactive MM and MGUS, whereas MMP-9 expression and secretion overlapped in all groups. Overall data suggest that patients with active MM represent the vascular phase of plasma cell tumors that is triggered by bone marrow plasma cells, at least partly, through FGF-2 and MMP-2. Both angiogenesis and MMP-2 secretion can account for intramedullary and extramedullary spreading of plasma cells during the active MM.
Chronic Eosinophilic Leukaemia Presenting with Erythroderma, Mild Eosinophilia and Hyper-IgE: Clinical, Immunological and Cytogenetic Features and Therapeutic Approach
Authors: Granjo E. , Lima M. , Lopes J.M. , Dória S. , Orfão A. , Ying Sun , Barata L.T. , Miranda M. , Cross N.C.P. , Bain B.J.
Published: April 2003

A 23-year-old, white male metallurgist presented with pruritic erythematous maculo-papules over the trunk and upper limbs and 6 months later developed erythroderma, eosinophilia and multi-organ dysfunction. A diagnosis of chronic eosinophilic leukaemia was made on the basis of myeloproliferative involvement of both peripheral blood and bone marrow, associated with eosinophilic differentiation and a t(5;12)(q33;p13) translocation. The initial therapeutic approach was interferon alfa-2b plus cytosine arabinoside, for 13 months, followed by hydroxyurea plus vincristine. There was improvement of skin lesions, disappearance of eosinophilia and decrease of serum immunoglobulin E, towards normal values.
Sustained Virological and Histological Response with Pretransplant Interferon Therapy in Renal Transplant Patients with Chronic Viral Hepatitis C
Authors: Huraib Sameer , Iqbal Aamir , Tanimu Danlami , Abdullah Abdulkader
Published: April 2003

Patients who are anti-HCV positive before renal transplantation (Tx) have a significantly increased risk of posttransplant liver disease. We conducted a prospective, controlled study to evaluate the posttransplant outcome of renal graft candidates with HCV-associated chronic hepatitis (n = 30). Patients were randomly assigned to either of two groups. All patients on enrollment underwent liver biopsy, which showed mild-to-moderate hepatitis activity (mean 4.1, range 2–6). Half the patients received interferon-alpha (IFN-a) administered at a dosage of 3 million units three times weekly for 1 year. Liver biopsy was repeated for treated patients at the end of IFN-a treatment. Of these, 11 patients received renal transplant (group A). The other half did not receive IFN-a and to date 10 patients have been transplanted (group B). Renal transplant recipients were prospectively followed for a period of 12 months and a follow-up liver biopsy was also done at the end of this period (end of study). Biochemical and virological responses were evaluated and the histologic activity index (HAI) scoring according to Knodell was assessed. The mean pretreatment serum HCV RNA level was 1.14 ± 0.84 and 1.0 ± 0.89 mEq/ml for groups A and B, respectively (bDNA assay sensitivity threshold is <0.2 mEq/ml). HCV RNA became undetectable in 4 patients of group A. At the end of study period the mean quantitative HCV RNA titers were 1.43 ± 4.07 and 15.18 ± 11.08 mEq/ml in groups A and B, respectively (p < 0.0001). In group A, the mean HAI score decreased from 4.27 ± 1.19 to 1.64 ± 0.67 after IFN-a treatment (p < 0.0001). This score was maintained till the end of the study period with a mean of 1.82 ± 0.6. Mean HAI score of group B on enrollment was 3.9 ± 1.2 and at the end of study increased to 5.5 ± 1.35 (p = 0.01). There was statistically significant difference (p value less than 0.0001) between the HAI scores at the end of the study period between the two groups. These results demonstrate that interferon therapy while on dialysis is associated with less viremia and decreased progression of chronic liver disease in renal transplant patients with hepatitis C.
Increased Production of Macrophage Migration Inhibitory Factor by T Cells in Patients with IgA Nephropathy
Authors: Matsumoto Koichi , Kanmatsuse Katsuo
Published: April 2003

Background/Aim: Several studies have demonstrated an upregulation of macrophage migration inhibitory factor (MIF) synthesis in experimental glomerulonephritis. To our best knowledge, no investigation of MIF production by T cells from patients with IgA nephropathy (IgAN) has been reported so far. MIF is one of the immunoregulatory cytokines involved in T-cell activation and delayed-type hypersensitivity. In this study, we examined MIF production of T cells from patients with IgAN to investigate the contribution of the cells to elevated serum MIF content and to its pathologic characteristics. Methods: We measured MIF production by T cells from the peripheral blood of 20 healthy controls and 20 patients with IgAN before and approximately 10 days after the beginning of steroid therapy. The disease controls included 20 patients with minimal-change nephrotic syndrome (MCNS) before therapy. MIF concentrations in the supernatants of T-cell cultures were measured with a specific enzyme-linked immunosorbent assay (ELISA). We also investigated the relationship between MIF levels and disease activity. Results: The mean level for MIF in patients with IgAN was significantly elevated compared with that of healthy controls and also higher than that of patients with MCNS. When T cells were stimulated by concanavalin A, MIF production by T cells of patients with IgAN was more enhanced than in control subjects or patients with MCNS. We also investigated the relationship between MIF levels and pathological features in IgAN patients. Our findings reveal that MIF levels correlated with the grade of glomerular crescent formation and immunofluorescent C3 deposits in the glomeruli. Moreover, MIF overproduction was significantly related to the acute exacerbation stage of IgAN patients. Elevated MIF levels during the acute phase or exacerbations were found to be decreased during spontaneous or steroid therapy-induced remission in all IgAN patients examined. Conclusions: We provide data indicating that a T-cell population isolated by negative selection from peripheral blood mononuclear cells shows increased in vitro production of MIF in IgAN, and a reduction in that production when patients are treated with corticosteroids. In this paper, we describe the hypothetical role of MIF in the pathophysiology of IgAN.
Serum Levels of Macrophage Colony-Stimulating Factor and Aortic Calcification in Hemodialysis Patients
Authors: Nitta Kosaku , Akiba Takashi , Kawashima Akira , Kimata Naoki , Miwa Naoko , Uchida Keiko , Honda Kazuho , Takei Takashi , Otsubo Shigeru , Yumura Wako , Kabaya Takashi , Nihei Hiroshi
Published: April 2003

Hemodialysis (HD) patients have accelerated atherosclerosis. Recent reports have shown that aortosclerosis is more frequently observed in HD patients than in healthy subjects. Macrophage colony-stimulating factor (M-CSF) secreted by activated macrophages may be involved in the process of aortosclerosis in HD patients. To understand the mechanism behind the increased incidence of aortosclerosis in HD patients, we examined the relationships between serum M-CSF levels and aortic calcification index (ACI) estimated by CT scan. A significant increase in serum M-CSF concentrations was found in HD patients (3.8 ± 0.2 ng/ml) as compared with controls (1.5 ± 0.1 ng/ml). No significant differences were observed between chronic glomerulonephritis and diabetes mellitus groups of patients. We also found no significant differences between the groups using different membranes (triacetate 3.8 ± 0.2 ng/ml vs. polysulfone 3.8 ± 0.4 ng/ml). There was no correlation between serum M-CSF concentrations and clinical parameters such as age, duration of HD, blood pressure, serum concentrations of nitrogen, creatinine, cholesterol, triglyceride, LDL, Ca × P products, and intact parathyroid hormone. A positive correlation was observed between serum M-CSF levels and ACI in HD patients (r = 0.596, p < 0.01). These results suggest that M-CSF may be involved in the process of aortosclerosis in HD patients.
Substance Use among Iranian Nephrologic Patients
Authors: Ahmadi Jamshid , Benrazavi Leila
Published: April 2003

Aims: This study assessed the prevalence of substance use among Iranian patients with nephrologic disease (chronic renal failure) who were admitted in different nephrologic wards at Shiraz general hospitals. Design: Cross-sectional survey using structured interview and also using DSM-IV criteria for substance dependency. Setting: General hospitals in Shiraz city (patients with nephrologic disease admitted in different nephrologic wards). Participants: 64 (32 men and 32 women) patients selected randomly. Findings: Data were gathered by a structured interview from 64 patients admitted in nephrologic wards of general hospitals in 2001. The mean age was 49.39 years (SD = 19.62) ranging from 18 to 80 years. 26 (40.6%) of the subjects (65.6% of the men and 15.6% of the women) reported the use of substance(s) once or more in their lives. The majority, 23 (35.9%) used tobacco, 9 (14.1%) used opium and 2 (3.1%) used alcohol. None had used cannabis, heroin, cocaine or LSD. 20 (31.3%) of the subjects (50% of the men and 12.5% of the women) were currently substance dependent, using DSM-IV criteria. The majority, 18 (28.1%) were nicotine dependent, and 6 (9.4%) were opium dependent. There was a nonsignificant relationship between income or occupation or education and prevalence of substance use. The reported reasons for initial use of substance(s), in order of frequency, were enjoyment, modeling and release of tension, and also for current users were, habit, enjoyment and need. Conclusions: Substance use especially cigarettes, opium and alcohol was found to be high among patients. There was no report of cannabis, heroin, cocaine or LSD use. Cultural attitudes toward substance use were found to affect the type and amount of use. These findings can be considered when planning preventive or therapeutic programs.
Correlation between Soluble Markers of Endothelial Dysfunction in Patients with Renal Failure
Authors: Jacobson Stefan H. , Egberg Nils , Hylander Britta , Lundahl Joachim
Published: April 2003

Aim: Damage to the endothelium is an important component of atherosclerosis. It has been suggested to be quantified by measuring plasma markers, such as von Willebrand factor and thrombomodulin and soluble adhesion molecules. We hypothesized there may exist a correlation between the plasma levels of von Willebrand factor and thrombomodulin as markers of endothelial cell dysfunction and the serum concentrations of soluble adhesion molecules and monocyte chemoattractant protein-1 (MCP-1) in patients with renal insufficiency, and in patients on peritoneal dialysis or hemodialysis since these three groups of kidney patients are highly prone to develop cardiovascular diseases. Results: The concentrations of von Willebrand factor and thrombomodulin in plasma were significantly higher in patients with kidney diseases as compared to healthy subjects (p = 0.017 and p < 0.001, respectively). The patients also had significantly higher concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and MCP-1 compared to healthy controls (p < 0.001 for both comparisons). There were strong correlations between the concentration of soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand factor in patients with kidney failure (r = 0.63, p < 0.001) and between the concentration of thrombomodulin and sVCAM-1 (r = 0.61, p < 0.001). Furthermore, a negative correlation was observed between the concentration of thrombomodulin and the cell surface expression of CD11b on monocytes and granulocytes in the peripheral circulation (p < 0.01 in both cases). Conclusion: The strong correlation between markers of endothelial dysfunction and soluble adhesion molecules in patients with renal insufficiency and on dialysis strengthen the view that an ongoing stress on endothelial cells is present in this group of patients. This may play a pathophysiological role in the development of cardiovascular disease.
High Endothelial Venule-Like Vessels in the Interstitial Lesions of Human Glomerulonephritis
Authors: Takaeda Masayoshi , Yokoyama Hitoshi , Segawa-Takaeda Chikako , Wada Takashi , Kobayashi Ken-ichi
Published: April 2003

To clarify the characteristics of high endothelial venule (HEV) -like vessels in the interstitium of human glomerulonephritis, we investigated the expression of HEVs related molecules such as P-selectin and L-selectin ligands; MECA-79 epitope and variant sulfated forms of sialyl Lewis X (variant sLeX, clones 2H5, 2F3, GS-13 and GS-36) in kidney specimens by means of immunohistochemical studies, and P-selectin and hevin mRNA signals by using in situ hybridization analyses. In lymphoid organs, HEVs strongly expressed P-selectin, MECA-79, variant sLeX and hevin mRNA signals. In normal kidneys (n = 4), only P-selectin was faintly positive in the vessels of interstitium, but other molecules could not be detected. Interstitial P-selectin expression was upregulated in patients with tubulointerstitial diseases (n = 4) and proliferative glomerulonephritis (n = 51) such as IgA-related nephropathy (n = 39), membranoproliferative glomerulonephritis (n = 4) and crescentic glomerulonephritis (n = 2), but not in nonproliferative glomerular diseases (n = 39) such as minimal change nephrotic syndrome (n = 18) (1.00 ± 0.41, 0.64 ± 0.11, 0.21 ± 0.05, respectively). Interstitial P-selectin expression also correlated with interstitial local cellular infiltration (r = 0.60, p < 0.0001). In addition, P-selectin mRNA signals were detected on the peritubular capillaries and HEV-like vascular endothelial cells. MECA-79 and variant sLeX (2H5 and 2F3) were weakly expressed on the HEV-like vessels located at the corticomedullary regions in three cases (7%) and in nine cases (27%) with interstitial cellular infiltration, respectively. However, we could not detect GS-13, GS-36 or hevin mRNA signals in the diseased kidney specimens. In conclusion, HEV-like vessels in renal interstitium expressed molecules somewhat different from HEVs in lymphoid organs and were associated with interstitial leukocyte accumulation in human proliferative glomerulonephritis possibly through the de novo expression of P-selectin and partly L-selectin ligands (MECA-79 epitope and variant sLeX) in the interstitial lesions.
Safety Aspects of Iron in Food
Authors: Schümann Klaus
Published: April 2003

During the last decades efforts regarding dietary iron supply focused mostly on the prevention of deficiencies, especially during growth and pregnancy. Correspondingly, homeostatic mechanisms increase intestinal iron absorption in iron deficiency, but its downregulation at high intake levels seems insufficient to prevent accumulation of high iron stores at high intake. There is no regulated iron excretion in overload. Excess of pharmaceutical iron may cause toxicity and therapeutic doses may cause gastrointestinal side effects. Chronic iron excess, e.g. in primary and secondary hemochromatosis, may lead to hepatic fibrosis, diabetes mellitus and cardiac failure. Chronic intake of 50–100 mg Fe/day of highly bioavailable iron with home-brewed beer in sub-Saharan Africans lead to cirrhosis and diabetes. Applying a safety factor of 2 would lead to an upper safe level of 25–50 mg Fe/day for this endpoint of conventional iron toxicity. However, beyond this kind of damage iron is known to catalyze the generation of hydroxyl radicals from superoxide anions and to increase oxidative stress which, in turn, increases free iron concentration. This self-amplifying process may cause damage to lipid membranes and proteins, which relates radical generation and organ damage after ischemia-reperfusion events to available free iron in clinical and experimental settings. Correspondingly, epidemiological studies as well as observations in heterozygotes for hereditary hemochromatosis suggest that the risk of atherosclerosis and acute myocardial infarction is related to body iron stores, though there is conflicting epidemiological evidence as well. The most recent and best controlled studies, however, support the hypothesis that iron stores are related to cardiovascular risk. Iron-amplified oxidative stress may also increase DNA damage, oxidative activation of precancerogens and support tumor cell growth. This is supported by experimental, clinical and epidemiological observations. Due to these mechanisms high iron stores may present a health hazard. Though this has not been finally proven, available evidence strongly recommends not to increase iron intake beyond physiological requirements. To avoid iron deficiency symptoms, on the other hand, care must be taken to meet recommended daily intake.
A Sucrose-Rich Diet during Pregnancy Causes a Similar Response in Sprague-Dawley and Wistar Rats
Authors: López-Soldado Iliana , Munilla Angeles , Herrera Emilio
Published: April 2003

Background/Aims: In order to determine whether the response to a sucrose-rich diet (SRD) during pregnancy in the rat varies depending on the strain, the responsiveness to a SRD (63 g sucrose/100 g) during pregnancy in Wistar and Sprague-Dawley rats was studied. Methods: One group of rats of each strain was fed the SRD, whereas another group received the same diet except that sucrose was replaced by an equal amount of cornstarch. Half of the rats were mated, and all animals were studied 20 days later. Results: Initial body weight did not differ among groups, but final body weight of pregnant Wistar rats was lower than in Sprague-Dawley, and this difference corresponded to a decrease in fetal body weight in the former. Feeding a SRD did not modify pregnancy outcome in either rat strain. Plasma triglycerides increased with a SRD, although this effect was milder in Wistar pregnant rats than in the other groups. Adipose tissue lipoprotein lipase activity was lower in pregnant than in virgin rats, but no differences were found as result of either diet or rat strain. Liver triglyceride concentration increased in virgin rats fed SRD, the effect being greater in Sprague-Dawley than in Wistar rats. Conclusion: Differences in the response to a SRD in pregnant and virgin rats do not depend on the strain of rats used.
Responses to Dietary Macronutrient Distribution of Overweight Rats under Restricted Feeding
Authors: Simón Edurne , del Puy Portillo María , Fernández-Quintela Alfredo , Zulet María A. , Martínez J. Alfredo , Del Barrio Antonio S.
Published: April 2003

Changes in protein and amino acid balance after energy-restricted feeding have scarcely been studied, although it has been suggested that protein utilization may depend on the macronutrient composition of the restricted diet. The aim of this study is to investigate the influence of dietary fat quality and content, during an energy-restricted regime, on body composition and protein metabolism. Therefore, diet-induced overweight rats were divided into three dietary groups: one group was fed on a control diet ad libitum (control) and the other two groups were fed energy-restricted diets (about 60% of control group), which provided a standard amount (20%) of fat (SFR), based on olive oil, or a high amount (60%) of saturated fat (HFR), based on coconut oil. Measurements of body weight, body composition, serum biochemical parameters and the assessment of the hepatic and muscular protein response were performed. Similar results were found comparing weight losses and serum parameters in both deprived groups, although the high-fat-restricted rats (HFR group) showed a greater reduction in the subcutaneous fat depot and of total body fat. After both energy-restricted treatments, the serum amino acid concentration was reduced while the urinary amino acid excretion increased. Muscle and liver protein metabolism was affected by energy restriction, which produced a decrease in protein synthesis capacity (RNA content) in both tissues and a higher muscle proteolysis (catepsin activity), more marked in the SFR group, while no changes were found in liver protein breakdown. Hepatic glycogen and glycogenic amino acid were also altered, reaching significant differences in the HFR group. Thus, dietary macronutrient composition during energy restriction seems to be involved in the metabolic adaptative response.