bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Dietary Protein on Eicosanoid Production in Rat Renal Tubules
Authors: Yanagisawa Hiroyuki , Wada Osamu
Published: April 2003

The effects of dietary protein on the in vitro production of prostaglandin (PG) E2, 6-keto PGF1α, and thromboxane B2 (TxB2) were examined in cortical and medullary tubules from rats fed a low (6% casein) or a high (40% casein) protein diet for approximately 8 weeks. PGE2 was a major eicosanoid produced by rat renal tubules (PGE2 > TxB2 > 6-keto PGF1α). Medullary tubules produced significantly greater amounts of PGE2, 6-keto PGF1α, and TxB2 than cortical tubules. The activity of phospholipase (PL) A2 and PLC and the levels of cyclooxygenase (COX) were significantly greater in medullary tubules than in cortical tubules. The production of eicosanoids may be increased in medullary versus cortical tubules via the greater activity of these enzymes involved in eicosanoid formation. Although there were no substantial differences in the production of PGE2, 6-keto PGF1α, and TxB2 between cortical tubules from rats fed a low- or a high-protein diet, significant increases in the synthesis of the three eicosanoids were observed in medullary tubules from rats fed a high- versus a low-protein diet. The activity of membrane-bound PLA2 and PLC and the levels of COX were not also substantially different between cortical tubules from rats fed a low- or a high-protein diet. However, medullary tubules had significantly greater activity of membrane-associated PLA2 and COX in rats fed a high-protein diet than in those fed a low-protein diet. The activity of PLC was comparable in medullary tubules from rats fed a low- or a high-protein diet. We conclude that a high protein intake selectively enhances eicosanoid production in rat medullary tubules probably via activation of the PLA2-COX pathway.
A Study of Ginsenoside-Rd in a Renal Ischemia-Reperfusion Model
Authors: Yokozawa Takako , Wu Liu Zhong , Dong Erbo
Published: April 2003

The effect of ginsenoside-Rd in ischemic-reperfused rats was examined. In control rats, blood and renal parameters and the activities of antioxidative enzymes in renal tissue deviated from the normal range, indicating dysfunction of the kidneys. In contrast, when ginsenoside-Rd was given orally for 30 consecutive days prior to ischemia and reperfusion, the activities of the antioxidation enzymes superoxide dismutase, catalase and glutathione peroxidase were higher, while malondialdehyde levels in serum and renal tissue were lower in the treated rats than in the controls. Decreased levels of urea nitrogen and creatinine in serum demonstrated a protective action against the renal dysfunction caused by ischemia and recirculation. On the other hand, it was demonstrated that ginsenoside-Rd affected cultured proximal tubule cells subjected to hypoxia-reoxygenation, probably by preventing oxygen free radicals from attacking the cell membranes.
Isolation of a Coronavirus from Kidney Biopsies of Endemic Balkan Nephropathy Patients
Authors: Uzelac-Keserović Branislava , Spasić Petar , Bojanić Nikola , Dimitrijević Jovan , Lako Branko , Lepsanović Zorica , Kuljić-Kapulica Nada , Vasić Duško , Apostolov K.
Published: April 2003

Endemic Balkan nephropathy (EBN) is a kidney disease of unknown etiology limited to Bulgaria, Rumania and former Yugoslavia. Primary kidney tissue cultures were established as explants from tissue obtained at operations from 5 EBN patients with urinary tract tumors. Four out of the five biopsy specimens on extended culture incubation at 33°C yielded a coronavirus virus (EBNV) which was cytopathogenic for human fibroblast and Vero cells. In cells inoculated with EBNV, cytoplasmic immunofluorescence was found using antisera for human coronaviruses OC43 and 229E as well as the porcine transmissible gastroenteric virus and avian (chicken) bronchitis virus. In neutralization tests, EBNV failed to react with antisera to these viruses. Using hyperimmune serum raised with EBNV, positive cytoplasmic immunofluorescence was seen with cells infected with OC43, 229E, TGV and significantly with the kidney tissue of the biopsy specimens from the EBN patients. A screen for neutralizing antibody using the EBN virus revealed that 87.2% of EBN patients on dialysis were positive, also 74% of people from an endemic area were also positive, while only 13.5% from outside were positive. It is suggested that a coronavirus is involved in the etiology of the disease and that humans are an incidental host of a coronavirus zoonosis.
Regression of Glomerular Injury by Kallikrein Infusion in Dahl Salt-Sensitive Rats Is a Bradykinin B2-Receptor-Mediated Event
Authors: Hirawa Nobuhito , Uehara Yoshio , Suzuki Tomohiko , Kawabata Yukari , Numabe Atsushi , Gomi Tomoko , lkeda Toshio , Kizuki Kazuyuki , Omata Masao
Published: April 2003

Aims: We investigated whether kallikrein infusion attenuates renal injury in Dahl salt-sensitive rats with hypertension and assessed the role of bradykinin-nitric oxide axis in the renal protection using HOE-140, the bradykinin type-2 (B2) receptor specific antagonist. Methods: Subdepressor dose of purified rat urinary kallikrein (RUK) (400 ng/day) was continuously infused through the jugular vein by an osmotic mini-pump for 4 weeks in Dahl salt-sensitive (Dahl S) rats fed a high-salt (2% NaCl) diet. Results: Blood pressure increased in a time-dependent manner in Dahl S rats fed a high-salt diet. The RUK infusion did not influence the elevation of blood pressure in Dahl S rats. However, the RUK infusion significantly decreased urinary protein excretion, and increased glomerular filtration rate, as compared with untreated high-salt Dahl S rats. Morphological investigation disclosed that the RUK infusion significantly attenuated glomerulosclerosis and arterial and tubular injuries in the kidney of hypertensive Dahl S rats. The RUK infusion produced an increase in urinary excretions of nitric oxide and cyclic guanosine monophosphate. In addition, the RUK infusion enhanced the generation of nitric oxide from the kidney slices. The functional and morphological effects of the RUK infusion on the kidney were completely lessened by co-administration of the bradykinin B2-receptor antagonist, HOE-140. Conclusion: Long-term infusion of subdepressor dose of rat urinary kallikrein attenuates functionally and morphologically the progression of renal injury in Dahl rats susceptible to salt-induced hypertension, and that the protection is mediated by stimulation of bradykinin B2 receptor.
Effects of Oral Administration of Heparan Sulphate in the Rat Remnant Kidney Model
Authors: Barsotti Giuliano , Cupisti Adamasco , Gervasi GianBattista , Bartoli Carlo , Barsotti Massimiliano , Pasquariello Antonio , Moriconi Luigi , Giovannetti Sergio
Published: April 2003

Heparins are useful for the protection of residual renal function in several nephropathies, but the anticoagulant action and the need of parenteral administration are two main drawbacks limiting their use in chronic renal failure patients. Heparan sulphate (HS) is a heparin-like mucopolysaccharide devoid of anticoagulant action and active orally. In this study, the effects of HS oral administration have been evaluated in 18 subtotally nephrectomized rats;18 untreated remnant kidney rats served as control. No mortality was observed in the HS-treated rats, whereas in the control rats the survival rate was 72.2% at 18 weeks. At the end of the study, HS-treated rats showed lower urinary protein excretion (44 ± 22 vs. 80 ± 54 mg/24 h , p < 0.01), lower urea plasma levels (75 ± 34 vs. 134 ± 105 mg/dl, p < 0.01) and higher creatinine clearance (66 ± 15 vs. 47 ± 21 ml/min · 102, p < 0.05) than control rats. Remnant kidney weight (2.3 ± 1.1 vs. 1.3 ± 0.2 g, p < 0.01) and heart weight (1.3 ± 0.2 vs. 1.1 ± 0.1 g, p < 0.05) were greater in the control than in the HS-treated rats, as well as the systemic blood pressure values (167 ± 19 vs. 115 ± 32 mm Hg, respectively, p < 0.001). The remnant kidney histological examination in the HS-treated rats showed a lower prevalence of glomerular sclerosis, mesangial proliferation, and a much less evident tubulointerstitial damage than in controls. The antiproliferative and anti-inflammatory actions of HS together with its protective action on the endothelium are the putative mechanisms that could account for our findings. In conclusion, the present study supports evidence of an antiproteinuric and a renoprotective effect of orally administered HS in subtotally nephrectomized rats. This is in keeping with the well-known effects exerted also by other heparins, but the effectiveness of an orally available heparin-like product in this animal model could suggest the possibility of a clinical use also in progressing chronic renal failure patients.
IgM/IgA Nephropathy in Callitrichids: Antigen Studies
Authors: Brack M. , Schroeder C. , Fooke M. , Schlumberger W.
Published: April 2003

Renal tissues of callitrichids with IgM nephropathy were immunohistochemically examined for the participation of IgA in pathogenesis. In 58 histopathologically nephropathy-positive kidneys, IgM predominated in 20 cases and IgA in 7 cases, and in 31 cases both immunoglobulins were rated to be approximately equally involved. The disease, therefore, might be described as IgM/IgA nephropathy. The renal tissues and sera were also tested for nutritional antigens or antinutritional antigen antibodies, using immunohistochemistry and Western blots (tissues) and enzyme-linked immunosorbent assay (sera). Evidences of nutritional antigens in the renal tissues were inconclusive, although circulating IgG class antibodies against cereals, milk, and egg proteins were present in quite a number of sera. Particular consideration was paid to IgA-antigliadin antibodies, which were statistically significantly associated with nephropathy as were IgA rheumatoid factors. The findings are discussed in relation to human IgA and IgM nephropathies.
HDL Cholesterol and TaqIB Cholesteryl Ester Transfer Protein Gene Polymorphism in Renal Transplant Recipients
Authors: Radeau T. , Vohl M.C. , Houde I. , Lachance J.G. , Noël R. , Després J.P. , Douville P. , Bergeron J.
Published: April 2003

Decreased serum levels of high-density lipoprotein cholesterol (HDL-C) are a well-known risk factor for coronary heart disease (CHD) in the general population and have been suggested as one of the best predictor of CHD after renal transplantation. However, very heterogeneous HDL-C levels have been reported in renal transplant recipients. In this patient population, serum HDL-C levels are determined by complex interactions between hormonal, environmental (such as a high amount of abdominal adipose tissue), and genetic factors and drugs (particularly glucocorticoids). We, therefore, evaluated the effects of the cholesteryl ester transfer protein (CETP) gene TaqIB polymorphism as well as of abdominal obesity on HDL-C levels in 78 male renal transplant recipients who were receiving azathioprine and/or ciclosporin A in combination with prednisone as immunosuppression. The patients were classified into genotypic groups according to the presence or absence of the restriction site (B1 allele or B2 allele, respectively). The distribution of CETP genotypes was similar to that previously described in the general population. Overall, HDL-C levels were 19 and 26% higher in B1B2 and B2B2 patients as compared with B1B1 homozygotes (p < 0.05), even after control for other lipid measurements. Patients with abdominal obesity (waist girth ≧93 cm) showed reduced HDL-C levels as compared with lean (waist girth <93 cm) patients (1.20 ± 0.28 vs. 1.42 ± 0.41 mmol/l, respectively, p < 0.01). Moreover, the HDL-C levels were markedly affected by the CETP TaqIB polymorphism in lean patients (+28 and +41% in B1B2 and B2B2 as compared with B1B1 patients, p < 0.05), but no significant difference was observed among obese patients. Significantly lower total cholesterol:HDL-C ratios were obtained in lean B2B2 homozygotes, suggesting that these patients could be less susceptible to atherosclerosis than lean B1B1 homozygotes. In addition, patients with the B1B1 genotype had more documented CHD as compared with patients carrying at least one B2 allele, supporting the protective effect of the B2 allele against CHD. In conclusion, considerable variation in HDL-C levels appears to be explained by the CETP TaqIB gene polymorphism in male renal transplant recipients, but this potential protective gene effect appears strongly reduced by concomitant abdominal obesity.
A Controlled Trial of the Effect of Folate Supplements on Homocysteine, Lipids and Hemorheology in End-Stage Renal Disease
Authors: McGregor David , Shand Brett , Lynn Kelvin
Published: April 2003

Elevated plasma homocysteine (Hcy), dyslipidemia and hemorheological abnormalities all occur commonly in end-stage renal disease (ESRD) and are recognized risk factors for arteriosclerosis. To study the effect of folate supplementation on these factors we conducted a randomized controlled trial. Thirteen hemodialysis (HD) and 8 continuous ambulatory peritoneal dialysis (CAPD) patients received either 5 mg folic acid daily or placebo for 3 months. After 1 and 3 months, fasting blood samples were taken for Hcy, lipid profile, blood and plasma viscosity, red blood cell (RBC) osmotic fragility, plasma fibrinogen concentration and in vivo platelet aggregability. At baseline, the CAPD patients had a higher mean plasma fibrinogen concentration than the HD patients and they also tended to have higher mean plasma viscosity. Folate-treated patients showed marked increases in RBC folate and an average decrease in plasma Hcy concentration of 33%. Mean total cholesterol, LDL cholesterol and triglyceride concentrations decreased significantly in the CAPD patients who took folate. Folate had no significant effect on hemorheology. In conclusion, folate supplements in ESRD reduce plasma Hcy concentrations and may improve lipid profiles. In our patients, hemorheological abnormalities were more marked in patients on CAPD than in those on HD and were not improved by folate supplementation.
Association of Angiotensin I Converting Enzyme Gene Polymorphism with Reflux Nephropathy in Children
Authors: Won Park Hye , Wook Koo Ja , Kim Jung Sue , Ha Il Soo , Cheong Hae Il , Choi Yong
Published: April 2003

Deletion polymorphism of angiotensin I converting enzyme (ACE) gene has been studied as a risk factor in various cardiovascular diseases and chronic nephropathies. Perturbation of local and systemic renin-angiotensin systems is one of the possible mechanisms of the progression of reflux nephropathy. In this study, the implication of ACE gene polymorphism in renal scarring and deterioration of renal function was analyzed in 66 children with vesicoureteral reflux. The genotype for the polymorphism was determined by PCR, and renal scar was identified by 99mTc-DMSA renal scan. The allelic frequency of the deletion polymorphism showed no significant difference either between patients with normal renal function and those with decreased renal function or between patients with renal scar and those without. We conclude that deletion polymorphism of ACE gene, as an independent variable, is not associated with reflux nephropathy in children with vesicoureteral reflux.
Molecular Mechanisms of Erythropoietin Signaling
Authors: Cheung Joseph Y. , Miller Barbara A.
Published: April 2003

Erythropoietin is an obligatory growth factor for red blood cell production. The receptor for erythropoietin contains a single membrane-spanning domain with no intrinsic tyrosine kinase motifs. On binding to erythropoietin, the receptor dimerizes and activates multiple intracellular signaling molecules, including but not limited to JAK2, STAT5, PI 3-kinase, IRS-2, RAS, and Ca2+ channels. This review focuses on cytoplasmic signaling cascades involved in erythropoietin action.
Modulation of Presbycusis: Current Status and Future Directions
Authors: Willott James F. , Hnath Chisolm Theresa , Lister Jennifer J.
Published: April 2003

Literature and ideas are reviewed concerning the modulation of presbycusis – the influence of variables that can alter the severity and/or time course of presbycusis or counteract its negative aspects. Eleven topics are identified: variables related to biological aging; genetics; noise-induced hearing loss; moderately augmented acoustic environment; neural plasticity and the central auditory system; neural plasticity and hearing aids; socioeconomic and cultural barriers to hearing aid use; lifestyle (diet, exercise, etc.); medical variables; pharmaceutical interventions for presbycusis, and cognitive variables. It is concluded that the field of otogerontology will best be served by a comprehensive, integrative interaction among basic researchers and clinical scientists who will continue to learn how the auditory problems associated with presbycusis can be intentionally modulated in beneficial ways.
Ultrastructural Changes of the Neuromuscular Junction in Reperfusion Injury
Authors: Tömböl T. , Pataki G. , Németh A. , Hamar J.
Published: April 2003

Ischemia followed by reperfusion of skeletal muscle frequently takes place in trauma surgery. Anoxia followed by reoxygenation leads to reperfusion injury, which damages the involved tissues. However, no information is available about how the neuromuscular junction is affected by ischemia-reperfusion. Tourniquet ischemia of the left hind limb was applied in the anesthetized rat for 2 h. Reperfusion lasted for 2 and 24 h and for 1, 2 and 4 weeks. The extensor digitorum longus and the soleus muscles from both legs were prepared for electron-microscopic analyses. Morphological changes of the neuromuscular junction were investigated. In all cases only the nerve endings (terminals) were affected. The postsynaptic structures were not affected. Changes can be grouped in two categories: degeneration and recovery. Degeneration consisted of the loss of synaptic vesicles, disruption of the presynaptic membrane, degeneration of the mitochondria and the development of vacuoles. It was most severe at 24 h and was still present at 4 weeks of reperfusion. Recovery started at 1 week of reperfusion and lasted at least for 4 weeks. It consisted of the slow reappearance of synaptic vesicles and mitochondria, and restoration of the presynaptic membrane with active zones. Ultrastructure of the skeletal muscle fibers did not show pathological changes. The recovery of the structures may be regulated by the Schwann cells and also by the postsynaptic membrane which is not affected by 2 h of ischemia followed by reperfusion.
Effects of Water Hardness on Urinary Risk Factors for Kidney Stones in Patients with Idiopathic Nephrolithiasis
Authors: Bellizzi Vincenzo , DeNicola Luca , Minutolo Roberto , Russo Domenico , Cianciaruso Bruno , Andreucci Michele , Conte Giuseppe , Andreucci VittorioE.
Published: April 2003

Both amount and timing of dietary calcium intake influence the recurrence of renal calcium stones. We have evaluated whether the hardness of extra meal drinking water modifies the risk for calcium stones. The urinary levels of calcium, oxalate and citrate, i.e., the main urinary risk factors for calcium stones, were measured in 18 patients with idiopathic nephrolithiasis, maintained at fixed dietary intake of calcium (800 mg/day), after drinking for 1 week 2 liters per day, between meals, of tap water and at the end of 1 week of the same amount of bottled hard (Ca2+ 255 mg/l) or soft (Ca2+ 22 mg/l, Fiuggi water) water, in a double-blind randomized, crossover fashion. As compared with both tap and soft water, hard water was associated with a significant 50% increase of the urinary calcium concentration in the absence of changes of oxalate excretion; the calcium-citrate index revealed a significant threefold increase during ingestion of hard water as compared with respect to soft water (Fiuggi water), making the latter preferable even when compared with tap water. This study suggests that, in the preventive approach to calcium nephrolithiasis, the extra meal intake of soft water is preferable to hard water, since it is associated with a lower risk for recurrence of calcium stones.
Chemical Analysis of Water of the Anticolana Valley: Isolation of Humic Compounds
Authors: Calace N. , D’Ascenzo G. , De Angelis Curtis S. , Delfini M. , Fraioli A. , Petronio B.M.
Published: April 2003

The purpose of this study was to identify and characterize humic compounds in Anticolana Valley (Fiuggi) water. The capacity of this class of compounds to mobilize metals from solid phases could have an important role in calculi solubilization. Humic compounds were isolated, purified and characterised by FTIR, 1H-NMR and 13C-NMR spectroscopy, thermogravimetry and elemental analysis. Only fulvic acids were found. They are mainly composed of aliphatic chains, made of six –CH2O– groups and contain a number of carboxylic groups, responsible for their metal complexing capacity.
Rapidly Progressive Glomerulonephritis due to Rifampicin Therapy
Authors: Yoshioka Keiji , Satake Norio , Kasamatsu Yoshihiro , Nakamura Yoshio , Shikata Nobuaki
Published: April 2003

A 60-year-old man was treated with rifampicin, isoniazid, ethambutol and pyrazinamide for pulmonary tuberculosis. Acute renal failure developed 1 month after re-administration of rifampicin following 1 month’s interruption of treatment. A renal biopsy showed crescentic lesions characteristic of rapidly progressive glomerulonephritis. This is, to our knowledge, the fourth case of rapidly progressive crescentic glomerulonephritis associated with rifampicin treatment, which responded to methylprednisolone pulse therapy followed by oral steroid therapy.
Epithelial Rests Colocalize with Cementoblasts Forming Acellular Cementum but Not with Cementoblasts Forming Cellular Cementum
Authors: Kagayama M. , Sasano Y. , Zhu J.-X. , Hirata M. , Mizoguchi I. , Kamakura S.
Published: April 2003

Epithelial rests of Malassez and cementoblasts were examined in the rat molars during the early stages of root formation using an antilaminin antibody and/or peanut agglutinin (PNA), and an antiosteocalcin (OC) antibody, respectively. The roots of the first molars were used for study. The antilaminin antibody stained the basement membrane surrounding the epithelial root sheath and epithelial rests. The basement membrane of the epithelial root sheath was continuous, but that of the epithelial rests was discontinuous. The cells of epithelial rests and epithelial root sheath were positive for PNA. The structural characteristics of the epithelial rests were seen in the sections stained doubly with PNA and the antilaminin antibody. The cells of epithelial rests were fibroblast-like and formed a fine mesh in 2-week-old rats. In 3-week-old rats, the epithelial rests were also present at the coronal half of root surface, showing typical cell cords, but were not present at the apical part of the root surface where the cellular cementum covered the root dentin. At the root apex of 3-week-old rats, the cells of epithelial rests forming fine meshes were seen near the epithelial root sheath. The anti-OC antibody stained cementoblasts lining acellular and cellular cementum. The sections doubly stained with the anti-OC and the antilaminin antibodies or PNA further revealed the close relation between epithelial rests and cementoblasts. The OC-positive cells lining acellular cementum or dentin were localized very close to the epithelial rests. In contrast, the OC-positive cells lining cellular cementum did not show close association with the epithelial cells, except the cells located most apically where the basement membrane of the epithelial root sheath is disrupted and the initial cellular cementum begins to be formed. The present results suggest that the epithelial rests and/or the discontinuous basement membrane of them may have a role for the acellular cementum formation at least in the early stage of root formation.
Lectin Ligands: New Insights into Their Conformations and Their Dynamic Behavior and the Discovery of Conformer Selection by Lectins
Authors: von der Lieth C.-W. , Siebert H.-C. , Kožár T. , Burchert M. , Frank M. , Gilleron M. , Kaltner H. , Kayser G. , Tajkhorshid E. , Bovin N.V. , Vliegenthart J.F.G. , Gabius H.-J.
Published: April 2003

The mysteries of the functions of complex glycoconjugates have enthralled scientists over decades. Theoretical considerations have ascribed an enormous capacity to store information to oligosaccharides. In the interplay with lectins sugar-code words of complex carbohydrate structures can be deciphered. To capitalize on knowledge about this type of molecular recognition for rational marker/drug design, the intimate details of the recognition process must be delineated. To this aim the required approach is garnered from several fields, profiting from advances primarily in X-ray crystallography, nuclear magnetic resonance spectroscopy and computational calculations encompassing molecular mechanics, molecular dynamics and homology modeling. Collectively considered, the results force us to jettison the preconception of a rigid ligand structure. On the contrary, a carbohydrate ligand may move rather freely between two or even more low-energy positions, affording the basis for conformer selection by a lectin. By an exemplary illustration of the interdisciplinary approach including up-to-date refinements in carbohydrate modeling it is underscored why this combination is considered to show promise of fostering innovative strategies in rational marker/drug design.
Signaling Pathways for Transduction of the Initial Message of the Glycocode into Cellular Responses
Authors: Villalobo A. , Gabius H.-J.
Published: April 2003

The sugar units of glycan structures store information and establish an alphabet of life. The language of the oligosaccharide coding units is deciphered by receptors such as lectins and the decoded message can be transduced by multiple signaling pathways. Similar to glycoconjugates, these receptors can exhibit pronounced changes in quantitative and qualitative aspects of expression, as attested by a wealth of lectin and immunohistochemical studies. Since histochemistry provides a static picture, it is essential to shed light on the mechanisms of how a recognitive protein-carbohydrate interplay can be transduced into cellular responses. Their consequences for example for cell morphology will then be visible to the histochemist. Therefore, basic signaling routes will be graphically outlined and their trigger potential will be explained by selected examples from the realm of glycosciences.
Structure and Functions of Lectins in the Central and Peripheral Nervous System
Authors: Zanetta J.-P.
Published: April 2003

There is increasing evidence that lectins are widely distributed in mammalian tissues, including the nervous tissue. Based on histochemical techniques using neoglycoproteins, different lectin activities specific for different monosaccharides or glycans have been identified (fucose, galactose, mannose, N-acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid and heparin). Most of them showed a cellular specificity and developmental regulation in the central nervous system. Several lectins isolated from the nervous tissue seem to play an essential role during ontogenetic processes, especially as far as cell adhesion and cell recognition mechanisms are concerned (axonal growth and fasciculation, neuron migration, synaptogenesis, myelination). But some of them seem to be involved in signaling events both intracellularly (nuclear lectins) or at the cell surface by autocrine and paracrine mechanisms. This review discusses the structure and the identified functions of these important constituents of the nervous tissue.
Glycobiology of the Olfactory System
Authors: Plendl J. , Sinowatz F.
Published: April 2003

The olfactory system is a highly plastic region of the nervous system. Continuous remodeling of neuronal circuits in the olfactory bulb takes place throughout life as a result of constant turnover of primary sensory olfactory neurons in the periphery. Glycoconjugates are very important in olfactory development, regeneration and function. This article deals with different aspects of glycobiology relevant for the olfactory system. Various anatomical, developmental and functional subdivisions of the olfactory system have been labeled with exogenous lectins. The application of reverse lectin histochemistry resulted in the visualization of endogenous lectins, involved in fasciculation of olfactory axons. Numerous glycoproteins, among them members of the immunoglobulin superfamily, the cadherins and integrins as well as different glycolipids and proteoglycans can act as surface adhesion molecules in the olfactory system. The olfactory-specific form of the sialoglycoprotein neural cell adhesion molecule is implicated in olfactory neuronal and axonal guidance. Glycoconjugates including laminin, fibronectin and proteoglycans are abundant components of the olfactory extracellular matrix, influencing neurite outgrowth and cellular migration. Immunohistochemical labeling has revealed occurrence of the carbohydrate differentiation antigen, playing a role in neurulation and morphogenesis of the very early olfactory system. The synaptic vesicle glycoprotein, appearing also early in olfactory development, is used as a marker of olfactory tumors. Finally, membrane and transmembrane glycoconjugates as well as secreted glycoconjugates may act as olfactory receptor molecules.
Variation in Sensitivity, Absorption and Density of the Central Rod Distribution with Eccentricity
Authors: Tornow R.P. , Stilling R.
Published: April 2003

Purpose: To assess the human rod photopigment distribution and sensitivity with high spatial resolution within the central ±15° and to compare the results of pigment absorption, sensitivity and rod density distribution (number of rods per square degree). Method: Rod photopigment density distribution was measured with imaging densitometry using a modified Rodenstock scanning laser ophthalmoscope. Dark-adapted sensitivity profiles were measured with green stimuli (17′ arc diameter, 1° spacing) using a Tübingen manual perimeter. Sensitivity profiles were plotted on a linear scale and rod photopigment optical density distribution profiles were converted to absorption profiles of the rod photopigment layer. Results: Both the absorption profile of the rod photopigment and the linear sensitivity profile for green stimuli show a minimum at the foveal center and increase steeply with eccentricity. The variation with eccentricity corresponds to the rod density distribution. Conclusion: Rod photopigment absorption profiles, retinal sensitivity profiles, and the rod density distribution are linearly related within the central ±15°. This is in agreement with theoretical considerations. Both methods, imaging retinal densitometry using a scanning laser ophthalmoscope and dark-adapted perimetry with small green stimuli, are useful for assessing the central rod distribution and sensitivity. However, at present, both methods have limitations. Suggestions for improving the reliability of both methods are given.
Immunological Problems of Transplantation into the Subretinal Space
Authors: Enzmann V. , Faude F. , Wiedemann P. , Kohen L.
Published: April 2003

The objective of retinal transplantation is to substitute destroyed or degenerated retina to improve visual function. Photoreceptors and retinal pigment epithelium cells of embryonic and nonembryonic origin have been transplanted into the subretinal space in different animal models. Recently, retinal cells have also been used for transplantation in untreated or immunosuppressed patients with retinitis pigmentosa and age-related macular degeneration. Transplants performed in animals such as the RCS rat have maintained retinal function at the transplantation site for long periods of time, although such transplantations in humans have not proved conclusively, to date, whether there is a real effect or not. One reason for this phenomenon seems to be an immune response to transplanted retinal cells at the transplantation site. The detectable rejection process shows that the posterior part of the eye is not absolutely immunologically privileged and that rejection is a serious problem in human retinal transplantation. Many questions concerning transplantation technique, graft treatment and postoperative treatment will be answered through more intensive experiments and clinical trials regarding the immunology. However, rejection of transplanted material is one of the main reasons why retinal transplantation has not yet proved successful.
Immunohistochemical Study of the Innervation of the Boundary Area of the Hard and Soft Palates of the Rat
Authors: Kato J. , Uddman R. , Sundler F. , Kurisu K.
Published: April 2003

The palatal mucosa plays an important role for patients using full dentures. The posterior ridge of the denture is designed to fit on the border between the hard and soft palates; accordingly, this boundary area is of importance when the outline of the denture is designed. In the present study, a rich supply of nerve fibers was found in the mucosa of the boundary area of the hard and soft palates of the rat. An immunocytochemical examination revealed nerve fibers containing protein gene product 9.5 (PGP 9.5), calcitonin gene-related peptide (CGRP), substance P (SP), pituitary adenylate cyclase-activating peptide, vasoactive intestinal polypeptide (VIP), C-terminal flanking peptide of neuropeptide Y (c-PON), or nitric oxide synthase (NOS). Thin nerve fibers with PGP 9.5, CGRP, or SP penetrated into the epithelium, reaching beneath the cornified layer and terminated as free nerve endings. VIP-, c-PON- and NOS-containing nerve fibers were distributed in the connective tissue. Many of the VIP- and c-PON-containing nerve fibers were associated with blood vessels. In addition, nerve fibers containing PGP 9.5, CGRP, SP and c-PON were observed around, and penetrating into, the taste buds in the boundary area.
The Neural Substrate for ‘Learned’ and ‘Nonlearned’ Activities in Birds: A Discussion of the Organization of Bulbar Reticular Premotor Systems with Side-Lights on the Mammalian Situation
Authors: Dubbeldam J.L.
Published: April 2003

The reticular formation of the brainstem contains premotor systems for various musculomotor systems. In this paper, the bulbar premotor systems for jaw and tongue movements, head and neck movements, locomotion, and respiration and vocalization in birds are reviewed and compared to premotor systems in mammals. Roughly, the bulbar reticular formation can be subdivided in three longitudinal zones: a dorsolateral (RPcdl) and a ventromedial (RPcvm) parvocellular zone and a gigantocellular zone (RGc). RPcdl contains premotor neurons for the jaw and neck system, RPcvm for the jaw, tongue and neck system, and RGc for the tongue and locomotory system. RPcdl receives input from the descending sensory trigeminal system, parts of RPcvm and RGc from vestibular nuclei, whereas the tectum has a projection to the contralateral RGc. RPcdl and RPcvm receive substantial telencephalic input through the occipitomesencephalic tract. The bulbar part of the respiratory system consists of a series of cell groups in the ventrolateral reticular formation and has connections with motor centers of the vocalization system. The similarities and differences between the avian and mammalian situation are discussed. Musculomotor systems participate in various activities. It is argued that a premotor system should possess sufficient flexibility to control the participation of a motor system in the different activities. This flexibility may permit the occurrence of learning processes in terms of refining basically existing motor patterns. The emergence of new and more complex motor patterns as in vocalization requires the involvement of hierarchically higher brain centers.
The UV-Responsive Melanocyte System: A Peripheral Network for Photoperiodic Time Measurements
Authors: Iyengar B.
Published: April 2003

Earlier studies indicate the involvement of indoleamines in the melanocyte photoresponse and cell cycle. In this study whole skin organ cultures were done to study the location of indoleamine expression during the photoresponse. Whole skin organ cultures from marginal zone vitiligo were incubated in MEM containing adriamycin and exposed to varying pulses of UV at 2 h of incubation. The G2 phase marginal melanocytes show increasing dendricity in response to increasing UV exposure at 3 h of incubation. On immunohistochemical staining for serotonin and melatonin, it is observed that both are positive in these melanocytes. The proportion of serotonin-positive melanocytes rises with increasing UV exposure while that of melatonin positivity rises with decreasing UV exposure, thus simulating the pineal response to light entrainment. This is due to photoinhibition of enzymes converting serotonin to melatonin. This study shows that the melanocytes in the skin can serve as the peripheral neural net for photoperiodic time measurements – the biological calendar.
Avascular Necrosis of the Hip in Children with Sickle Cell Disease and High Hb F: Magnetic Resonance Imaging Findings and Influence of α-Thalassemia Trait
Authors: Adekile A.D. , Gupta R. , Yacoub F. , Sinan T. , Al-Bloushi M. , Haider M.Z.
Published: April 2003

Avascular necrosis (AVN) of the hip is a common cause of morbidity in sickle cell disease (SCD). Its prevalence increases with age and predisposing factors include coexistent α-thalassemia trait, frequent vaso-occlusive crisis and a high hematocrit (Hct). SCD is relatively mild among Kuwaiti patients because of their elevated Hb F levels, but a subset exists with severe recurrent vaso-occlusive crises. We carried out a prospective magnetic resonance imaging (MRI) study of the hip in a group of patients being followed in the Pediatric Hematology clinics of Al-Mubarak and Al-Amiri Hospitals. The association of AVN with age, frequency of hospitalization, α-thal trait, steady-state Hb, Hct, Hb F, WBC and platelet counts was investigated. MRI was carried out with a 1.5-tesla GE unit with a super-conducting magnet. Thirty patients (19 males, 11 females) (23 SS and 7 SβThal) were studied. Their ages ranged from 6 to 17 years, with a mean of 9.8 ± 3.5 years, and Hb F from 11 to 35% with a mean of 22.8 ± 5.7%. Among the SS patients, 11 (47.8%) had coexistent α-thal trait (–3.7-kb deletion). A total of 8 (26.7%) patients (6 SS and 2 SβThal) had varying degrees of osteonecrosis of the hip. Four (36.4%) of the 11 SS patients with α-thal trait and 2 (16.7%) of those without α-thal trait had osteonecrosis. This difference is, however, not statistically significant (χ2 = 0.3, p = 0.5). While there was also no significant difference in the mean age and hematological parameters (Hb, Hct, Hb F, WBC, platelets), the SS patients with osteonecrosis had a significantly higher number of hospitalizations for vaso-occlusive crisis in the preceding 3 years than those without osteonecrosis.
The Thrombophilic State in Cancer Patients
Authors: Gouin-Thibault I. , Achkar A. , Samama M.M.
Published: April 2003

Thrombosis and disseminated intravascular coagulation are common complications of cancer. Specific conditions associated with cancer such as stasis due to immobilization or blood flow obstruction, surgery, infections, endothelium damage due to chemotherapeutic agents and abnormalities of blood coagulation contribute to the hypercoagulable and thrombophilic state of cancer patients. This procoagulant state in cancer arises mostly from the capacity of tumor cells to express and release procoagulant activities (cancer procoagulant and tissue factor). Decreased levels of inhibitors of coagulation, impaired fibrinolysis, the presence of antiphospholipid antibodies and an acquired activated protein C resistance contribute to the hypercoagulable state. The activation of coagulation is also implicated in tumor proliferation through interactions of coagulation with inflammation and increased tissue factor pathway inhibitor. Laboratory diagnosis of the thrombophilic state include (1) elevation of clotting factors, fibrinogen/fibrin degradation products, hyperfibrinogenemia and thrombocytosis and (2) elevation of specific markers of activation of coagulation: fibrinopeptide A, fragment 1 + 2, thrombin-antithrombin complexes and D-dimers. However, none of the tests has any predictive value for the occurrence of thrombotic events in one individual patient. In patients with venous thromboembolism a noninvasive screening for occult cancer is able to detect a relatively high incidence of hidden cancer and the search for thrombophilia seems important in patients without known cancer.
Thrombotic Microangiopathy in the Cancer Patient
Authors: Kwaan Hau C. , Gordon Leo I.
Published: April 2003

Thrombotic microangiopathy, manifesting as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome, is a common complication in cancer patients. It shares the pathogenic microvascular occlusive lesion and many clinical manifestations as the classical TTP, but the spectrum of complications varies widely. Several subsets are seen, including a microangiopathic hemolytic anemia in advanced cancer, chemotherapeutic drug-associated microangiopathy and those with the transplant setting. The prognosis is not as favorable as in classical TTP. Anecdotal reports indicate that responses are seen with plasma exchange and with immunoadsorption.
Generation of Dendritic Cells from Leukaemia Cells of a Patient with Acute Promyelocytic Leukaemia by Culture with GM-CSF, IL-4 and TNF-α
Authors: Narita Miwako , Takahashi Masuhiro , Liu Aichun , Ayres Flavio , Satoh Naoko , Abe Takashi , Nikkuni Kohji , Furukawa Tatsuo , Toba Ken , Aizawa Yoshifusa
Published: April 2003

Dendritic cells are potent antigen-presenting cells derived from CD34+ haemopoietic stem cells. Dendritic cells have been reported to be generated from cells in granulocytic lineage as well as monocytes, blood dendritic cell precursors and lymphoid progenitors. In order to explore the differentiation pathway of dendritic cells from granulocytic cells and the applicability of leukaemia-derived dendritic cells for anti-leukaemic immunotherapy in acute leukaemia of granulocytic origin, we tried to generate dendritic cells from leukaemia cells of a patient with acute promyelocytic leukaemia (APL). Leukaemia cells were cultured with GM-CSF, IL-4 and TNF-α for 10 days. Azurophilic granule-containing cells with marked cytoplasmic projections were generated in the culture. FACS analysis of these cultured cells revealed the generation of CD1a+, CD83+, CD80+, CD86+, CD40+ and HLA-DR+ cells. The leukaemic origin of these dendritic-like cells was demonstrated by in situ hybridization of magnetic-bead-sorted CD1a+ dendritic cells using the DNA probes of t(15;17). Cells generated by culturing leukaemia cells were demonstrated to have a potent antigen-presenting function in allogeneic mixed leucocyte cultures. These findings show the plausibility of the previously reported pathway of dendritic cell maturation through granulocytic cells and suggest the possibility of anti-leukaemic immunotherapy using leukaemia-derived dendritic cells even in patients with acute promyelocytic leukaemia.
Myeloproliferative Disorders with Translocations of Chromosome 5q31–35: Role of the Platelet-Derived Growth Factor Receptor Beta
Authors: Steer E. Joanna , Cross Nicholas C.P.
Published: April 2003

Acquired reciprocal chromosomal translocations that involve chromosome bands 5q31–33 are associated with a significant minority of patients with BCR-ABL-negative chronic myeloid leukemias. The most common abnormality is the t(5;12)(q33;p13), which fuses the ETV6/TEL gene to the platelet-derived growth factor receptor-β (PDGFRB), a receptor tyrosine kinase that maps to 5q33. PDGFRB is disrupted by other translocations and to date four additional partner genes (H4, HIP1, CEV14 and Rab5) have been reported. Clinically, most patients present with a myeloproliferative disorder (MPD) with eosinophilia, eosinophilic leukemia or chronic myelomonocytic leukemia and thus fall into the broader category of myeloproliferative disorders/myelodysplastic syndromes (MPD/MDS). With the advent of targeted signal transduction therapy, patients with rearrangement of PDGFRB might be better classified as a distinct subgroup of MPD/MDS.
Severe Coombs’-Negative Autoimmune Hemolytic Anemia in a Kidney Transplant Patient
Authors: Shnaider Alla , Basok Anna , Rogachev Boris V. , Zlotnik Moshe , Tomer Aaron
Published: April 2003

Background/Aim: Few cases are found in the literature regarding autoimmune hemolytic anemia which is Coombs’ test positive in kidney transplant patients, although hemolytic uremic syndrome due to cyclosporin and FK506 has been well described. In the following, we describe a case of severe life-threatening Coombs’ test negative autoimmune hemolytic anemia after kidney transplantation. Methods: Soon after undergoing renal transplantation, the patient presented with hemolytic anemia. Kidney biopsy, routine Coombs’ test, gel filtration and flow-cytometric assay were undertaken. Results: Kidney biopsy ruled out hemolytic uremic syndrome; although Coombs’ test and gel filtration assay were negative, flow cytometry revealed circulating antierythrocytic autoantibodies. Conclusions: Our findings indicate that flow cytometry may be an efficient method in the diagnosis of hemolysis of unknown origin in transplant patients. We further hypothesize that the underlying mechanism of autoimmune hemolytic anemia is related to the passenger B lymphocytes in the graft.
Influence of Highly Active Antiretroviral Therapy on Micronutrient Profiles in HIV-Infected Patients
Authors: Rousseau M.C. , Molines C. , Moreau J. , Delmont J.
Published: April 2003

Objectives: To assess micronutrient variations in HIV/AIDS patients before and after HAART (highly active antiretroviral therapy). Methods: We evaluated the nutritional status and micronutrients in 44 patients over 3 years. The first nutritional evaluation was conducted in 1995 before HAART, the second was conducted in 1998 when most patients received HAART. Results: Thirty-four (77%) of the patients were intravenous drug users. In 1995, 35 (80%) were receiving antiretroviral therapy, but none had a protease inhibitor. A comparison made between patients in the group with CD4 <250/mm3 (group A) and patients in the group with CD4 >250/mm3 (group B) revealed significantly lower levels of plasma selenium concentrations (p < 0.05). In group A women, zinc was significantly lower than in men of the same group (p < 0.05). On the contrary, selenium plasma concentrations were significantly lower in group A men than in group A women (p < 0.05). No significant differences were noted for other micronutrients. In 1998, when most patients were treated with HAART, differences between the two groups were no more significant, neither for selenium nor for zinc matched with sex. Micronutrient values did not significantly differ between patients with viral load below 5,000 copies/ml and patients with viral load above 5,000 copies/ml. Patients treated with HAART had practically no weight loss. Although patients who did not receive HAART had a good immune status, the mean weight loss was up to 4.6 kg. Conclusions: Selenium and zinc deficiencies are dependent on immune status and sex in HIV/AIDS patients. Other micronutrients do not seem to be influenced by the immune status in these patients. HAART reduces selenium and zinc deficiencies and may help avoid weight loss independently of the CD4 cell count.