bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrinolysis Defect in Long-Term Hemodialysis Patients with Type 2 Diabetes mellitus and Its Relation to Metabolic Disorders
Authors: Opatrný  Jr. Karel , Zemanová Pavlína , Mareš Jan , Vít Ladislav , Opatrná Sylvia , Šefrna František , Hejda Václav , Tomšů Martina , Eiselt Jaromír , Massry Shaul G.
Published: April 2003

Background/Aims: Patients with chronic renal failure (CRF) secondary to diabetes mellitus show a high incidence of atherosclerosis with its thrombotic complications. Both CRF and type 2 diabetes mellitus (DM2) results in fibrinolysis defects causally related to atherogenesis and thrombogenesis. It is not well known whether or not and, if so, how fibrinolysis is altered in patients with both CRF and DM2. Our study was designed (1) to identify the fibrinolysis defect present in patients with DM2-mediated CRF and treated by long-term hemodialysis (DM2HD), and (2) to establish whether the fibrinolysis defect is related to the metabolic abnormalities observed in CRF or DM2. Methods: Sixteen DM2HD patients and 23 healthy individuals (HI) had their euglobulin clot lysis time (ECLT), and tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) activities (act) and concentrations (ag) assessed before and after standard fibrinolytic stimulus (i.v. administration of 0.4 µg/kg BW 1-deamino-8-D-arginine vasopressin, DDAVP) along with metabolic status markers. Results: DDAVP caused a significant shortening of ECLT, rises in tPA act and ag, and a significant decrease in PAI-1 act. PAI-1 ag declined significantly in HI, but not in DM2HD. A comparison of responses to DDAVP revealed the groups differed significantly in the change in PAI-1 ag. Whereas, in HI, PAI-1 ag decreased by 11.8 ng/ml, no decrease was seen in DM2HD (0.0 ng/ml) (p < 0.0001; medians given; unpaired Wilcoxon’s test). Stepwise regression analysis showed the change in PAI-1 ag was highly group-specific (DM2HD vs. HI, regression coefficient 21.22; partial correlation 0.58; p < 0.0001) and, also dependent on the serum concentrations of apolipoprotein A-I (–32.41; –0.46; p < 0.01) and homocysteine (0.35; 0.36; p < 0.05). Conclusions: Patients with type 2 DM and CRF on long-term hemodialysis have a fibrinolysis defect manifesting itself after standard fibrinolytic stimulus by an insufficient decrease in PAI-1 concentrations. The defect is related to decreased serum levels of apolipoprotein A-I and increased serum levels of homocysteine. The defect might be a factor contributing to accelerated atherosclerosis and thrombotic complications in these patients.
Regulation of Inducible Class II MHC, Costimulatory Molecules, and Cytokine Expression in TGF-β1 Knockout Renal Epithelial Cells: Effect of Exogenous TGF-β1
Authors: Banu Nazifa , Mozes Miklos M. , Kopp Jeffrey B. , Ziyadeh Fuad N. , Meyers Catherine M.
Published: April 2003

As reports of mice genetically deficient for TGF-β1 demonstrated aberrant renal class II MHC expression, we investigated inducible class II MHC expression on renal tubular epithelial cells derived from TGF-β1 knockout (–/–) and wild-type (+/+) mice. IFN-γ markedly upregulated class II MHC (I-Ab) expression in both (–/–) and (+/+) tubular epithelial cells. Coincubation studies of (+/+) and (–/–) tubular epithelial cells with IFN-γ+LPS, or pretreatment of these cells with TGF-β1, revealed inhibition of IFN-γ-induced I-Ab mRNA and cell surface expression that occurred via a decrease in class II transactivator gene expression in both (+/+) and (–/–) tubular epithelial cells. In addition, ICAM-1 was constitutively expressed on both (+/+) and (–/–) tubular epithelial cells and was upregulated by IFN-γ or IFN-γ+LPS. ICAM-1 expression in (+/+) and (–/–) tubular epithelial cells, however, was decreased by TGF-β1. Parallel analysis evaluating B7-1 expression detected low levels of B7-1 in unstimulated (+/+) and (–/–) tubular epithelial cells that were increased by IFN-γ, LPS, and IFN-γ+LPS. IFN-γ+LPS-mediated upregulation of B7-1 was also blocked by pretreatment with TGF-β1. Cytokine analysis detected significantly higher levels of TNF-α and MIP-1α mRNA in all treated (–/–) preparations than in (+/+) tubular epithelial cell controls. These studies demonstrate normal patterns of class II MHC, ICAM-1, and B7 expression in TGF-β1 (–/–) tubular epithelial cells in response to IFN-γ, LPS, and TGF-β1. Upregulated cytokine expression at baseline and in response to proinflammatory mediators is apparent in (–/–) tubular epithelial cells, however, and suggests that dysregulation of cytokine expression in inflammatory responses may be a primary event in multifocal inflammation observed in TGF-β1-deficient animals.
Preserved Endothelium-Dependent but Impaired β-Adrenergic Relaxation of the Resistance Vessels in Experimental Renal Failure
Authors: Jolma Pasi , Kalliovalkama Jarkko , Tolvanen Jari-Petteri , Kööbi Peeter , Kähönen Mika , Saha Heikki , Pörsti Ilkka
Published: April 2003

Chronic renal failure is associated with increased cardiovascular morbidity and reduced arterial elasticity. Only little information is available on the functional effects of uraemia on resistance arteries. Therefore, we studied the influence of renal failure on rat small mesenteric vessels. The responses of arterial rings were investigated in a Mulvany myograph 6 weeks after 5/6 nephrectomy or sham operation. The subtotal nephrectomy resulted in a 1.9-fold elevation of plasma urea nitrogen but was without significant effect on blood pressure. Endothelium-dependent relaxations, largely mediated via arterial K+ channels, were preserved in the resistance vessels of uraemic rats. Endothelium-independent vasorelaxations, mediated via exogenous nitric oxide and the opening of ATP-sensitive K+ channels, were also unchanged. However, the responses induced by isoprenaline were slightly reduced, indicating impaired relaxation via β-adrenoceptors in experimental renal failure.
Unexpected Renal Actions of Erythropoietin
Authors: Westenfelder Christof
Published: April 2003

Erythropoietin (EPO) in the renal cortex is synthesized by fibroblast-like cells that are in direct contact with capillaries and adjacent tubular cells. Prompted by this anatomical relationship, we asked whether renal cells express EPO receptors (EPORs) through which EPO could act as a renotropic cytokine. We found that all regions of human, rat and mouse kidney, mesangial and proximal and distal tubular cells express authentic EPORs. Similar EPOR expression was detected in kidney cancer cells, and in cyst epithelia from polycystic kidneys. In vitro, EPO stimulated mitogenesis in all normal and malignant cells, and cell survival and motogenesis in injured tubular cells. Since the normal kidney is essentially unresponsive to EPO, we hypothesized that EPO’s cytokine effects in the kidney are revealed when tubular cells are induced to proliferate by a prior insult, as occurs in acute renal failure. Accordingly, we found that EPO treatment of rats with ‘ischemic’ acute renal failure afforded renoprotection and accelerated functional recovery.
Basic Rules of Parenteral Fluid Therapy
Authors: Oh Man S. , Kim Ho-Jung
Published: April 2003

The following basic rules of parenteral fluid therapy are formulated with the aim of alleviating concern and confusion about i.v. fluid orders that are experienced by most physicians: Don’t be generous with fluid; in determining the water intake, one must know the usual water output through the kidney, skin and lung; one must know the quantities of the electrolytes and nutrients that are being given, and know the initial volume of distribution (usually the ECF); one must know the aim of fluid therapy; one must not give and remove the same substance at the same time; one must be aware that hypertonic saline contains less water for a given amount of Na than isotonic saline; one must be familiar with different i.v. solutions and i.v. additives; one must be aware that the kidney does not manufacture water or electrolytes except for bicarbonate; for short-term fluid therapy, divalent ions (Ca, Mg, and P) do not need replacement; one should think about COP-wedge gradient in determining the type of fluid to be given.
The Coincidence of Fetal Magnetocardiography and Direct Electrocardiography in a Case of Fetal Atrial Flutter due to Intracardiac Tumor
Authors: Hosono Takayoshi , Kanagawa Takeshi , Chiba Yoshihide , Kandori Akihiko , Tsukada Keiji
Published: April 2003

Objective: To demonstrate the coincidence of fetal magnetocardiography (FMCG) and fetal direct electrocardiography (FDECG) in a case of fetal atrial flutter (AF). Methods: FMCG and FDECG using a fetal scalp electrode were recorded in the case of fetal AF at 41 weeks’ gestation. Results: FMCG revealed fetal AF with 2:1 atrioventricular block, which was also documented by FDECG using a fetal scalp electrode. The prenatal diagnosis was confirmed by postnatal electrocardiogram. Neonatal echocardiography revealed an intracardiac tumor on the left atrial septum. The tumor seemed to be the cause of AF. Conclusion: FMCG may provide the same information as a fetal electrocardiogram in the prenatal diagnosis of fetal AF.
Prenatal Diagnosis of Zygosity by Fetal DNA Analysis, a Contribution to the Management of Multiple Pregnancies
Authors: Levy Ronaldo , Mirlesse Véronique , Jacquemard François , Daffos Fernand
Published: April 2003

Objective: To evaluate the contribution of prenatal diagnosis of zygosity by fetal DNA analysis to the management of multiple pregnancies. Methods: Between March 1999 and March 2000, 31 same-sex multiple pregnancies, were referred to our Institute during their second trimester to have amniocentesis done. Fetal DNA variants were studied in addition to karyotype. The main indications for amniocentesis were fetal growth discordance, fetal malformations or selective pregnancy termination. Zygosity results were compared to the first-trimester ultrasound diagnosis. Results: 21 out of the 31 multiple pregnancies were dizygous, and 10 out of the 31 pregnancies were monozygous. First-trimester ultrasound provided information on chorionicity only in 24 out of the 31 cases (77%). Of these 24 reports, 21 proved to be correct (87.5%). Moreover, in 2 cases among 14 pregnancies with growth discordance, DNA analysis ruled out a twin-to-twin transfusion syndrome, while ultrasound could not yield a conclusion. In 2 twin pregnancies with fetal malformations affecting one of the fetuses, DNA analysis made it possible to assess the risk for the other twin. In the 5 cases leading to selective termination, prenatal diagnosis of zygosity had a decisive value for the surviving fetus. Conclusion: Fetal DNA analysis is a simple and highly useful test for prenatal diagnosis of zygosity in the management of complicated multiple pregnancies.
Craniopharyngioma Involving the Infrasellar Region
Authors: Fujimoto Yasunori , Matsushita Hamilton , Velasco Octávio , Rosemberg Sérgio , Plese José Píndaro , Marino Jr. Raul
Published: April 2003

Craniopharyngiomas are most commonly located in the intradural suprasellar region. However, ectopic craniopharyngiomas can originate in the infrasellar region. The authors present the case of an 8-year-old boy diagnosed with a large cystic craniopharyngioma involving the nasal cavities and maxillary, ethmoid and sphenoid sinuses, in addition to the sella turcica. The primary symptoms of this patient were nasal obstruction, unilateral decreased visual acuity and exophthalmos. He subsequently underwent combined radical resection of the tumor by means of an endonasal transsphenoidal approach followed by radiation therapy. During the surgery, the dura mater of the sellar floor was found to be intact. The neuroradiological and surgical findings suggested that this tumor originated in the extradural infrasellar region and invaded the sella turcica.
Innate Immunity Associated with Inflammatory Responses and Cytokine Production against Common Dietary Proteins in Patients with Autism Spectrum Disorder
Authors: Jyonouchi Harumi , Sun Sining , Itokazu Nanae
Published: April 2003

Objectives: Children with autism spectrum disorder (ASD) frequently reveal various gastrointestinal (GI) symptoms that may resolve with an elimination diet along with apparent improvement of some of the behavioral symptoms. Evidence suggests that ASD may be accompanied by aberrant (inflammatory) innate immune responses. This may predispose ASD children to sensitization to common dietary proteins (DP), leading to GI inflammation and aggravation of some behavioral symptoms. Methods: We measured IFN-γ, IL-5, and TNF-α production against representative DPs [gliadin, cow’s milk protein (CMP), and soy] by peripheral blood mononuclear cells (PBMCs) from ASD and control children [those with DP intolerance (DPI), ASD siblings, and healthy unrelated children]. We evaluated the results in association with proinflammatory and counter-regulatory cytokine production with endotoxin (LPS), a microbial product of intestinal flora and a surrogate stimulant for innate immune responses. Results: ASD PBMCs produced elevated IFN-γ and TNF-α, but not IL-5 with common DPs at high frequency as observed in DPI PBMCs. ASD PBMCs revealed increased proinflammatory cytokine responses with LPS at high frequency with positive correlation between proinflammatory cytokine production with LPS and IFN-γ and TNF-α production against DPs. Such correlation was less evident in DPI PBMCs. Conclusion: Immune reactivity to DPs may be associated with apparent DPI and GI inflammation in ASD children that may be partly associated with aberrant innate immune response against endotoxin, a product of the gut bacteria.
Colchicine-Induced Myopathy with Normal Creatine Phosphokinase Level in a Renal Transplant Patient
Authors: Caglar Kayser , Safali Mükerrem , Yavuz Izzet , Odabaşi Zeki , Yenicesu Müjdat , Vural Abdülgaffar
Published: April 2003

A case of a renal transplant recipient with colchicine-induced myopathy is presented. He was on colchicine therapy for 10 months. He was hospitalized for investigation of fatigue, severe myalgia in the lower extremities and elevated serum aminotransferase levels. His viral markers and other factors that may cause myalgia and that may increase the serum aminotransferase levels were either normal or negative. Creatine phosphokinase (CK) levels were normal. Electrophysiological findings indicated myopathy and muscle biopsy was consistent with vacuolar myopathy. After withdrawal of colchicine, the symptoms disappeared gradually and serum aminotransferase levels were normalized. We suggest that colchicine myopathy should be taken into account in patients who have been on colchicine therapy and had unexplained myalgia as well as elevated aminotransferase levels even with normal CK levels.
Exogenous Nitric Oxide Inhibits Tumor Necrosis Factor-Alpha- or Interleukin-1-Beta-Induced Monocyte Chemoattractant Protein-1 Expression in Human Mesangial Cells
Authors: Lee Sang Koo , Kim Choung Soo , Yang Won Seok , Kim Soon Bae , Park Su-Kil , Park Jung Sik
Published: April 2003

Monocyte chemoattractant protein-1 (MCP-1) plays an important role in glomerulonephritis and nitric oxide (NO) exerts a variety of renal pathophysiological effects. We investigated the effect of exogenous NO on pro-inflammatory cytokine-induced MCP-1 expression in human mesangial cells and its signal transduction pathway. Cells were pretreated with NO donors such as 3-morpholino-sydnonimine (SIN-1) or nitroprusside, and then stimulated with tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β). MCP-1 expression of mRNA and protein were measured by Northern blot analysis and ELISA. NF-ĸB binding activity was determined by electrophoretic mobility shift assay. Degradation of IĸB-α protein was assessed by Western blot analysis. SIN-1 inhibited TNF-α- or IL-1β-induced MCP-1 mRNA expression in a dose-dependent manner and also suppressed the MCP-1 protein expression. Nitroprusside inhibited the MCP-1 mRNA expression as well. SIN-1 dose dependently inhibited the TNF-α- or IL-1β-induced NF-ĸB binding activity and suppressed the TNF-α-induced degradation of IĸB-α. Analogue of cGMP (8-bromo-cGMP) had no significant effect on TNF-α-induced MCP-1 mRNA expression and guanylate cyclase inhibitor (ODQ) also had no significant influence on the inhibitory effect of SIN-1. These results suggest that exogenous NO inhibits MCP-1 expression via suppression of NF-ĸB by reducing the degradation of IĸB-α and through a cGMP-independent pathway.
Different Effects of Castration and Estrogen Administration on Glomerular Injury in Spontaneously Hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) Rats
Authors: Tomiyoshi Yoshiyuki , Sakemi Takanobu , Aoki Shigehisa , Miyazono Motoaki
Published: April 2003

Aim: Non-insulin-dependent diabetic mellitus model rats, Otsuka-Long-Evans-Tokushima-Fatty (OLETF), develop diabetic nephropathy presenting with mesangial expansion leading to glomerular sclerosis and thickening of the glomerular basement membrane (GBM), especially in elderly males. The effects of sex hormones and castration on the incidence of diabetes mellitus (DM) have been studied in this strain rat. However, there have been no detailed studies on the effects of castration and sex hormone in the development of diabetic nephropathy. Methods: In this study we examine the effect of castration or estrogen on the development of glomerular injury in OLETF rats. Thirty male OLETF rats and 10 male long-Evans Tokushima Otsuka (LETO) rats as a normal control were used. OLETF rats were divided into three groups: group 1 received sham-operation, group 2 was castrated at 6 weeks, and group 3 was administered 0.1 mg estrogen subcutaneously once a month from 6 weeks to 58 weeks of age and LETO rats were assigned to group 4. Body weight, urinary protein and fasting blood glucose, serum albumin and other serum constituents were investigated every 12 weeks from 12 weeks to 60 weeks of age. In groups 1–3, glucose tolerance test was performed at 38 weeks. Each group was studied morphologically at the end of the experiment (60 weeks of age). Results: Castration attenuated proteinuria and glomerular sclerosis accompanied by an amelioration of glucose tolerance, a decrease in mesangial expansion and an attenuation of the GBM thickening. In contrast, although estrogen equally ameliorated glucose tolerance and attenuated the mesangial expansion and the GBM thickening, estrogen failed to attenuate proteinuria and glomerulosclerosis. A significant increase in glomerular tuft volume, and serum levels of growth hormone, total cholesterol and triglycerides was observed in the estrogen-treated rats as compared with the castrated rats. Conclusion: Besides the mechanisms involved in the development of diabetic nephropathy, other mechanisms may be involved and contribute to the development of glomerulosclerosis in the estrogen-treated rats, leading to a difference in glomerular injury between the castrated and estrogen-treated OLETF rats.
Hyperphosphatemia Modestly Retards Parathyroid Hormone Suppression during Calcitriol-Induced Hypercalcemia in Normal and Azotemic Rats
Authors: Jara Aquiles , Chacón Cecilia , Felsenfeld Arnold J.
Published: April 2003

Background/Aims: In in vitro studies, a high phosphate concentration has been shown to directly stimulate parathyroid hormone (PTH) secretion in a normal calcium concentration and to reduce PTH suppression in a high calcium concentration. In hemodialysis patients during dialysis-induced hypercalcemia, the effect of hyperphosphatemia on PTH secretion was less than in vitro studies. Our goal was to determine whether hyperphosphatemia retards PTH suppression during calcitriol-induced hypercalcemia in azotemic rats with hyperparathyroidism. Methods: Rats underwent a two-stage 5/6 nephrectomy or sham operations. After surgery, rats received a high phosphate diet (P 1.2%, Ca 0.6%) for 4 weeks to induce hyperparathyroidism and then were placed on a normal diet (P 0.6%, Ca 0.6%) for two additional weeks to normalize serum calcium values in azotemic rats. At week 7, rats were divided into five groups and before sacrifice received at 24-hour intervals, three doses of calcitriol (CTR) or its vehicle. The five groups and dietary phosphate content were: group 1 – normal renal function (NRF) + 0.6% P + vehicle; group 2 – NRF + 0.6% P + CTR; group 3 – renal failure (RF) + 0.6% P + vehicle; group 4 – RF + 1.2% P + CTR; and group 5 – RF + 0.6% P + CTR. Results: In the two CTR-treated groups with marked hypercalcemia (groups 2 and 5), 15.52 ± 0.26 and 15.12 ± 0.13 mg/dl, respectively, stepwise regression showed that hyperphosphatemia retarded PTH suppression. When the two azotemic groups treated with CTR (groups 4 and 5) were combined to expand the range of serum calcium values, stepwise regression showed that hypercalcemia suppressed and hyperphosphatemia modestly retarded PTH suppression. Similarly, in groups 4 and 5 combined, correlations were present between PTH and both serum calcium (r = –0.70, p < 0.001) and serum phosphate (r = 0.64, p = 0.001). Conclusions: Hypercalcemia and high doses of calcitriol markedly reduced PTH secretion in azotemic rats despite severe hyperphosphatemia. Even though hyperphosphatemia did retard PTH suppression during hypercalcemia, its effect was small.
Suppressive Effects of Rosmarinic Acid on Mesangioproliferative Glomerulonephritis in Rats
Authors: Makino Toshiaki , Ono Takahiko , Liu Ning , Nakamura Tomoko , Muso Eri , Honda Gisho
Published: April 2003

Background: Rosmarinic acid is known to be a natural phenolic compound widely distributed in Labiatae herbs such as rosemary, sweet basil, and perilla. In the present study, we evaluated the suppressive effects of rosmarinic acid on mesangioproliferative glomerulonephritis in vivo, which was induced by intravenous injection of rabbit anti-rat thymocyte serum (ATS) to rats. Methods: Rosmarinic acid was orally administered to the rats at a dose of 100 mg/kg/day from the day of ATS injection (day 0) to day 8 when rats were sacrificed. The degree of mesangial cell proliferation and matrix accumulation were evaluated by trichrome staining and by immunostaining for proliferating cell nuclear antigen (PCNA), fibronectin, type IV collagen and fibrin. Superoxide dismutase (SOD)-activity in the homogenate of renal cortex was also evaluated. Results: The number of PCNA-positive cells, staining areas of trichrome, fibronectin, collagen IV and fibrin in the glomerulus were significantly decreased, and SOD-activity of renal cortex homogenate was significantly augmented in rosmarinic acid-treated group. Conclusion: Rosmarinic acid would suppress the proliferation of mesangial cells and glomerular matrix expansion in vivo by its fibrinolytic and anti-oxidative activity.
Distinct Role of Nitric Oxide and Endothelium-Derived Hyperpolarizing Factor in Renal Microcirculation
Authors: Ozawa Yuri , Hayashi Koichi , Nagahama Takahiko , Fujiwara Keiji , Kanda Takeshi , Homma Koichiro , Saruta Takao
Published: April 2003

Background: Both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) are established as important factors determining the vascular tone. The relative contribution of these factors to the renal microvascular tone, however, has not been delineated. Methods: Isolated perfused hydronephrotic rat kidneys were used to characterize the relative role of NO and EDHF in mediating the tone of interlobular arteries (ILA) and afferent arterioles (AFF). Results: During the norepinephrine constriction, acetylcholine (ACH, 1 µmol/l) induced a sustained vasodilation of ILA (90 ± 9% reversal) and AFF (117 ± 13% reversal). In the presence of nitro-L-arginine methylester (LNAME), the ACH-induced vasodilation of ILA and AFF was converted to transient dilation, with only 53 ± 7 and 32 ± 7% reversal observed 10 min after 1 µmol/l ACH (i.e sustained phase). In contrast, LNAME had no effect on the initial phase of ACH-induced dilation. In the presence of apamin + charybdotoxin, the initial vasodilator response to ACH (1 µmol/l) was diminished (ILA, from 108 ± 8 to 46 ± 9%; AFF, from 108 ± 14 to 58 ± 8%), whereas no impairment was observed in sustained phases. Furthermore, the magnitude of the vasoconstriction caused by LNAME was greater at smaller vessel segments. Finally, the LNAME-induced inhibition of the sustained phase of ACH-induced vasodilation was greater as the vessel diameter decreased. Conclusions: That the relative contribution of NO and EDHF differs, with a greater role of NO in the basal tone and ACH-induced vasodilation at smaller vascular segments of ILA and AFF.
Urinary Concentrations of Alpha-1-Microglobulin and Albumin in Patients with Reflux Nephropathy before and after Puberty
Authors: Konda Ryuichiro , Kakizaki Hidehiro , Nakai Hideo , Hayashi Yutaro , Hosokawa Shozo , Kawaguchi Satoru , Matuoka Hirofumi , Nonomura Katsuya
Published: April 2003

We determined urinary concentrations of α1-microglobulin and albumin in 155 patients with reflux nephropathy including 72 prepubertal (48 males and 24 females) and 83 postpubertal patients (43 males and 40 females) to elucidate the effect of age and gender in the progression of renal damage. Vesicoureteral reflux was resolved in all patients at least two years before enrollment into this study. Renal scarring was diagnosed with 99mtechnetium dimercaptosuccinic acid renal scan. More severe renal scarring was found predominantly in male compared to female patients. Urinary α1-microglobulin levels were significantly lower in postpubertal female patients (mean ± SD: 1.59 ± 1.02 mg/g creatinine) than in prepubertal males and females (3.32 ± 3.53 and 4.06 ± 4, respectively; p < 0.007 and p < 0.002, respectively), and in postpubertal males (3.69 ± 2.6; p < 0.002) regardless of severity of renal scarring. In the patients with severe unilateral renal scarring, urinary albumin levels were significantly higher in postpubertal males (81.9 ± 239.5) than in prepubertal males and postpubertal females (25.8 ± 63.1 and 13.8 ± 7.7, respectively; p < 0.05 and p < 0.05, respectively). Our results suggest that glomerular injury may develop during adolescence predominantly in male patients with severe renal scarring. In contrast, renal damage indicated by urinary α1-microglobulon level appears to be ameliorated in female postpubertal patients. This gender difference may be attributed to sex hormones.
Follow-Up with Serum Cyfra 21-1 in Patients with Squamous Cell Carcinomas of the Head and Neck
Authors: Kuropkat C. , Lippert B.M. , Werner J.A.
Published: April 2003

Objective: Finding tumor markers for disease progression, and especially development of distant metastases, is desirable for patients with squamous cell carcinoma of the head and neck (SCCHN). Elevated serum levels of Cyfra 21-1 (cytokeratin fraction 21-1) have been frequently associated with disease progression in patients with lung cancer. In SCCHN, Cyfra 21-1 has not been established as a routine tumor marker yet, probably due to difficulties in finding the appropriate cut-off for the serum level. The aim of this study was to investigate whether assessment of changes in serum Cyfra 21-1 over time can predict distant metastases in patients with SCCHN, without attempting to establish an arbitrary cut-off for abnormal levels. Methods: Cyfra 21-1 serum levels of 25 patients with SCCHN and distant metastases were evaluated by means of an ELISA test kit. Results: There was a wide range of Cyfra 21-1 serum levels at the time of primary diagnosis, without correlation with tumor size, lymph node status, time to recurrence, or presence of distant metastases. All patients had a clear increase of Cyfra 21-1 levels which preceded the appearance of distant metastases clinically. Conclusions: Due to the wide range of Cyfra 21-1 levels at the time of primary tumor diagnosis, Cyfra-21-1 is neither a suitable screening marker for SCCHN, nor for diagnosis of distant metastases at the time of initial diagnosis of the tumor, but is of evident prognostic value for follow-up, especially for early detection of distant metastases.
Effects of Interleukin-1-Beta, Interleukin-6 and Tumor Necrosis Factor-Alpha, Alone or in Association with Hexarelin or Galanin, on Growth Hormone Gene Expression and Growth Hormone Release from Pig Pituitary Cells
Authors: Mainardi Gian Luca , Saleri Roberta , Tamanini Carlo , Baratta Mario
Published: April 2003

Objective: We studied the effects of IL-1β, IL-6 and TNF-α on GH gene expression and secretion with or without galanin and hexarelin. Methods: Pituitary cells from adult pigs were treated with IL-1β, IL-6 or TNF-α (1, 10 and 100 ng/ml), alone or in association with galanin or hexarelin (10–8M): GH mRNA was measured by RT-PCR and GH secretion by ELISA. Results: IL-1β (1, 10 and 100 ng/ml) and IL-6 (1 and 10 ng/ml) significantly (p < 0.05) enhanced GH output. IL-1β and TNF-α (1 and 10 ng/ml) reduced (p < 0.05) the galanin-induced GH secretion and IL-6 (10 ng/ml) potentiated the effect of both GH releasers (p < 0.05). GH gene expression was increased only by IL-6 at the concentrations of 1 and 10 ng/ml, either alone or in association with both galanin and hexarelin. Conclusions: We hypothesize that cytokines may play a paracrine/autocrine role in GH regulation in the pituitary independently from the intracellular pathways of the GH secretagogues.
Evidence for Human Leukocyte Antigen-Related Susceptibility in Idiopathic Childhood Ischemic Stroke
Authors: Zou Li-Ping , Guo Yu-Hong , Fang Fang , Jin Hong , Wu Hu-Sheng , Mix Eilhard
Published: April 2003

Stroke in children is a relatively uncommon condition and frequently associated with other diseases like cardiopathies, sickle cell disease and chronic smoking. In contrast to stroke in adults, it is rarely caused by atherosclerosis, hypertension or diabetes mellitus. Childhood stroke of unknown causes is called idiopathic stroke. The etiology of idiopathic stroke is unknown. However, several so-called idiopathic diseases develop on the basis of a genetic predisposition. As an approach to investigate this possibility in idiopathic childhood ischemic stroke, we studied the relationship between clinical and immunogenetic features in this disease. We demonstrate that the gene frequencies and relative risk of HLA-B51 were markedly increased in our patients compared with controls (p < 0.001). Thirteen of seventeen HLA-B51-positive patients had had a preceding respiratory infection, which was a higher proportion than in the control group (p < 0.05). In the patient group, the alleles HLA-DRB1*0802, -DRAI*0401 and -DQBI*0402 were also significantly increased, defining the haplotype DRB1*0802-DRA1*0401-DQB1*0402 as a high-risk haplotype for idiopathic childhood ischemic stroke. Transient viral or bacterial infections, which involve vasculitis and vascular occlusion in the brain, can trigger idiopathic childhood ischemic stroke on the basis of an genetic predisposition.
Use of Pedicle Flap from the Labia minora for the Repair of Female Urethral Strictures
Authors: Tanello M. , Frego E. , Simeone C. , Cosciani Cunico S.
Published: April 2003

Introduction: We present the method of pedicle labial urethroplasty for urethral reconstruction in female patients treated for urethral strictures. Patients and Methods: We performed urethral reconstruction using a pedicle labial flap in 2 female patients (23 and 70 years old) for urethral stricture (posttraumatic and postinflammatory origin). We used as a patch a pedicle skin flap obtained from the labia minora. The pedicle flap is slid beneath the vulvovaginal wall, until the urethra is reached. Results: In both cases a normal micturition was obtained, and cystourethrography after 24 months showed a good urethral silhouette, without residual urine. Conclusion: The pedicle labial urethroplasty seems to be a reliable technique for the repair of urethral strictures.
Importance of Transition Zone Biopsies in Patients Undergoing Ultrasound-Guided Prostate Systemic Biopsies for the First Time
Authors: Ishizuka O. , Iijima K. , Ishikawa M. , Hirakata S. , Nagai T. , Ueki T. , Nishizawa O.
Published: April 2003

Introduction: We analyze the efficacy of routine transition zone biopsies in patients undergoing ultrasound-guided systemic prostate biopsies for the first time because of a suspicious digital rectal examination or an elevated serum prostate-specific antigen (PSA) level. Patients and Methods: During systemic prostate biopsy two or four additional transition zone biopsies were performed in 192 consecutive patients: in 182 because of a serum PSA concentration >4.1 ng/ml and in 10 because of a suspicious digital rectal examination and a serum PSA level <4.0 ng/ml. Results: The overall prostate cancer detection rate was 37.5% (72/192). In 24 patients (33.3%), cancer was only detected in the peripheral zone, in 3 (4.2%) only in the transition zone, and in 45 (62.5%) in both zones. Conclusion: Transition zone biopsies performed at the first time of systemic prostate biopsy seem to have a low efficacy.
A Reevaluation of the Structures Accepted to Represent the Postnatal Gubernaculum
Authors: Tanyel F. Cahit , Talim Beril , Kale Gülsev , Büyükpamukçu Nebil
Published: April 2003

Introduction: The structure called the residual gubernaculum (G) has been evaluated to define its origin. Materials and Methods: Girls operated for inguinal hernia (n = 7) and boys operated for undescended testis (n = 12), inguinal hernia (n = 7), hydrocele of the cord (n = 1), and ectopic (n = 1) and entrapped (n = 1) testes were evaluated. Attachments of the structures coursing distally from the sacs were identified, and they were removed en block. Three samples, first from the distal part of the sac with the beginning of the fibrous structure, second from the midportion, and third from the most distal part, were prepared and stained with hematoxylin-eosin, trichrome and elastic van Gieson. Histologic structures within the samples were determined and compared with Mann-Whitney U test. Results and Conclusions: Structures called the residual G differed from the walls of accompanying sacs by only the absence of mesothelial lining. Therefore, the structure called the residual G in boys with an undescended testis and the round ligament in girls actually represent the obliterated processus vaginalis.
Subsequent Activation of Mitogen-Activated Protein Kinase after Adhesion of Transitional Cell Cancer Cells to Fibronectin
Authors: Saito Toshihiro , Tomita Yoshihiko , Kawasaki Takashi , Bilim Vladimir , Takahashi Kota
Published: April 2003

Introduction: In the process of tumor invasion and metastasis, interactions between tumor cells and extracellular matrix play a crucial role. Recently, it was shown that fibronectin binding to fibronectin receptor promotes mitogen-activated protein kinase (MAPK) activation after tyrosine phosphorylation of focal adhesion kinase (FAK). We investigated these signal transduction events in transitional cell cancer (TCC) cells. Materials and Methods: (1) The adhesion of T24 cells, a fibronectin-receptor-positive TCC cell line, to fibronectin was investigated; (2) the MAPK activation after fibronectin stimulation in bladder cancer cell lines was examined by Western blotting using an antiactive MAPK antibody, and (3) FAK, Sos, and Grb-2 were also examined by Western blot analysis. Results and Conclusions: T24 cells adhered to fibronectin-coated dishes more quickly than to the noncoated dishes. Fibronectin stimulation induced activation of MAPK in T24, SCaBER, and HT1376 cells. However, activated MAPK was not detected in RT4 cells which do not express α5β1 integrin (major fibronectin receptor) after fibronectin stimulation. T24, SCaBER, and HT1376 expressed FAK and Sos. RT4 showed little FAK and Sos expression. Grb-2 was expressed in all cell lines. Adhesion of fibronectin-receptor-positive TCC cells to fibronectin activates the MAPK cascade, possibly resulting in activation of tumor cells.
Early and Late Complications of Double Pigtail Ureteral Stent
Authors: Damiano Rocco , Oliva Andrea , Esposito Ciro , De Sio Marco , Autorino Riccardo , D’Armiento Massimo
Published: April 2003

Objectives: To analyze the early and late complications of indwelling ureteral stents in a series of 146 patients with nephroureteral lithiasis. Materials and Methods: 146 patients with obstructing nephrolitiasis were treated for urinary diversion with double pigtail ureteral stent before extracorporeal shock-wave lithotripsy (ESWL) and following ureterorenoscopic treatment of lithiasis. All patients were scheduled for stent removal or replacement at specific 3-month intervals until stone-free status was achieved. Results: Early complications during the first 4 weeks after stent insertion were stent discomfort (37.6%), irritative bladder symptoms (18.8%), hematuria (18.1%), bacteriuria (15.2%), fever >104F (12.3%) and flank pain (25.3%); late complications included hydronephrosis (5.7%), and stent migration (9.5%), encrustation (21.6%), fragmentation (1.9%) and breakage (1.3%). Conclusions: Ureteral stents have proven to be an invaluable tool for endourologists. Morbidity is minimal for up to three months but longer indwelling times are associated with an increasing frequency of incrustation, infections, secondary stone formation and obstruction of the stented tract.
Giant Calculus of the Posterior Urethra following Recurrent Penile Urethral Stricture
Authors: Hegele A. , Olbert P. , Wille S. , Heidenreich A. , Hofmann R.
Published: April 2003

A case of an unusually large, proximal urethral calculus located very close to the external sphincter and caused by recurrent urethral stricture is presented.
Improved Quality of Life in Patients with Refractory or Recidivant Ascites after Insertion of Transjugular Intrahepatic Portosystemic Shunts
Authors: Gülberg Veit , Liss Ingrid , Bilzer Manfred , Waggershauser Tobias , Reiser Maximilian , Gerbes Alexander L.
Published: April 2003

Background: We have recently shown that the transjugular intrahepatic portosystemic shunt (TIPS) is more effective than paracentesis in the treatment of cirrhotic patients with severe ascites and can prolong survival in selected patients. Although an improved quality of life (QOL) has been suggested in these patients after the TIPS procedure, so far there are no data available to substantiate this assumption. Therefore, the aim of this study was to determine the effect of TIPS on the QOL in cirrhotic patients with refractory or recidivant ascites. Methods: 21 cirrhotic patients who underwent TIPS for refractory or recidivant ascites were investigated. All patients were pretreated with repeated paracentesis for at least 1 year. Before the procedure and at 3 and 6 months during follow-up, the patients themselves rated QOL, fatigue and physical performance on a visual analogue scale (range 0–100). Furthermore, QOL was determined by the QOL index (range 0–10) according to Spitzer. Results: Patients’ rating of the QOL on the visual analogue scale significantly increased from 35 ± 25 (baseline) to 64 ± 28 (3 months), and 66 ± 24 (6 months; p = 0.02). Similarly, the QOL index significantly increased from 6.9 ± 2.0 (baseline) to 8.3 ± 2.1 (3 months), and 8.6 ± 1.7 (6 months; p < 0.001). The increase of QOL was more pronounced in patients with complete response to TIPS. Conclusions: We demonstrate that TIPS for refractory or recidivant ascites improves the QOL in patients with cirrhosis. Our data indicates that this improvement is dependent on the response to therapy.
Polymorphisms in the von Willebrand Factor Gene Are Not Associated with Proliferative Retinopathy in Non-Insulin-Dependent Diabetes mellitus
Authors: Beránek Michal , Kaňková Kateřina , Kolář Petr , Znojil Vladimír
Published: April 2003

Von Willebrand factor, a multimeric glycoprotein synthesized mainly by endothelial cells, is involved in platelet adhesion and aggregation and has an important role in the process of angiogenesis. Increased levels of von Willebrand factor, reflecting activation or damage of endothelial cells, have been described in association with proliferative diabetic retinopathy (PDR). We investigated the relationships of two polymorphisms (–1793G/C and Thr789Ala) in the von Willebrand factor gene with PDR. Genotypes were detected by polymerase chain reactions with subsequent restrictions with specific endonucleases. Allele frequencies were determined in an association study (n = 371) comprising three groups of subjects (diabetics with and without retinopathy and nondiabetics). Allele frequencies of the –1793G/C and Thr789Ala did not differ between the non-insulin-dependent diabetes mellitus (NIDDM) + PDR and the NIDDM non-PDR groups (p > 0.05). However, a statistically significant difference in allele and genotype frequencies of the –1793G/C was proved between all NIDDM versus nondiabetic subjects (p = 0.024 and 0.0065, respectively) with allele G and genotype GG being significantly more frequent in the NIDDM group. Calculated odds ratio for the GG genotype was 1.20 (95% CI, 0.77–1.86). Although significantly higher plasma von Willebrand factor antigen levels in NIDDM patients with PDR have been described in several studies, our findings indicate that no association exists between the two polymorphisms and PDR. However, the –1793G/C polymorphism might affect the risk of NIDDM.
Effects of Elevated Pressure on Prostanoid Receptor Gene Expression Levels in Human Trabecular Meshwork
Authors: Schneemann Andrea , Hoyng Philip F.J. , Kamphuis Willem
Published: April 2003

The purpose of this study was to assess the effects of increased intraocular pressure on the expression levels of the prostanoid receptor genes (DP, EP1–4, FP, IP, TP) in the trabecular meshwork of human donor eyes. Anterior segments of human donor eyes were perfused in an ex vivo anterior segment perfusion system under different pressure regimes. The expression levels of the prostanoid receptors and of several housekeeping genes were assessed by non-competitive real-time quantitative polymerase chain reaction (Q-PCR). Perfusion of the anterior segments for 24 h at 10 mm Hg, followed by 24 h at 30 mm Hg, caused a significant decrease in the expression of the EP2 receptor compared to a constant perfusion under 10 mm Hg. No significant changes were found for the other prostanoid receptor transcripts. When the pressure was raised to 30 mm Hg for only 1 or 3 h, no changes in the EP2 receptor expression levels were evident. However, a transient DP and TP receptor expression increase was found after 1-hour perfusion at 30 mm Hg. Whether these changes in expression are part of a response of the trabecular meshwork cells in order to normalise intraocular pressure needs to be studied further.
Effect of Simultaneous CGRP and PGF2α on the Outflow Facility in the Rabbit Eye
Authors: Alajuuma Päivi , Oksala Olli , Alaranta Sakari , Palkama Arto , Uusitalo Hannu
Published: April 2003

Both calcitonin gene-related peptide and prostaglandins have an influence on the intraocular pressure in the eye. In this study, the effects of low intracameral doses (20 ng and 50 ng) of calcitonin gene-related peptide, prostaglandin F2α, and simultaneous dosing of both, on the outflow facility were studied in the rabbit. Calcitonin gene-related peptide increased the outflow facility at both 20 and 50 ng doses, while prostaglandin F2α increased it only at a 50 ng dose. Further, simultaneous administration of both at 50 ng doses increased the outflow facility and showed a slight additive effect with these two compounds. The results further indicate that these compounds have a different mechanism of action. Calcitonin gene-related peptide seems to increase the conventional outflow (trabecular outflow), while prostaglandin F2α tends to increase the unconventional outflow (uveoscleral outflow).
Risk Factors for Cryptogenic and Idiopathic Partial Epilepsy: A Community-Based Case-Control Study in Copparo, Italy
Authors: Casetta Ilaria , Monetti Vincenza C. , Malagù Susanna , Paolino Ezio , Govoni Vittorio , Fainardi Enrico , Tola Maria R. , Granieri Enrico
Published: April 2003

Objectives: The etiology of epilepsy remains unknown in most cases. We sought to investigate the role of some pre-, peri- and postnatal factors in the etiology of idiopathic and cryptogenetic partial epilepsy. Methods: We carried out a community-based case-control study using the incidence cohort of epileptic patients living in the district of Copparo, in the province of Ferrara, Italy. The study was performed in 55 cases and 165 controls. A standardized questionnaire was used to collect information in face-to-face interviews. Results: Multivariate logistic regression analysis found that a personal history of febrile convulsions [odds ratio (OR) = 4.01, 95% confidence interval (CI) = 1.3–19.1] and a family history of seizures in first-degree relatives (OR = 4.5, 95% CI = 1.8–18.6) were independent risk factors for the condition under study. We failed to demonstrate an association between partial epilepsy and previously suggested perinatal risk factors. Conclusion: The findings of this study further support the hypothesis of a genetic propensity for seizures, which may be expressed early by the occurrence of febrile convulsions.
Roles of Hematopoietic Transcription Factors GATA-1 and GATA-2 in the Development of Red Blood Cell Lineage
Authors: Ohneda Kinuko , Yamamoto Masayuki
Published: April 2003

The transcription factors GATA-1 and GATA-2 play key roles in gene regulation during erythropoiesis. Gene ablation studies in mouse revealed that GATA-2 is crucial for the maintenance and proliferation of immature hematopoietic progenitors, whereas GATA-1 is essential for the survival of erythroid progenitors as well as the terminal differentiation of erythroid cells. Both GATA-1 and GATA-2 are regulated in a cell-type-specific manner, their expression being strictly controlled during the development and differentiation of erythroid cells. Closer examination revealed a cross-regulatory mechanism by which GATA-1 can control the expression of GATA-2 and vice versa, possibly via essential GATA binding sites in their cis-acting elements. In addition, recent studies identified several human inherited hematopoietic disorders that are caused by mutations in cis-acting GATA binding motifs or mutations in GATA-1 itself.
Changes in the Expression of Cytoskeletal Proteins in the CNS of Transferrin Transgenic Mice
Authors: Marta C.B. , Ortiz E.H. , Hallak M. , Baron B. , Guillou F. , Zakin M.M. , Soto E.F. , Pasquini J.M.
Published: April 2003

Apotransferrin injected intracranially into young rats has been shown in our laboratories to induce an early differentiation of oligodendroglial cells and an increased deposition of myelin. The expression of some myelin-specific proteins such as myelin basic protein (MBP) and 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) and of their mRNAs were significantly increased in these animals. Also, in the cytoskeleton obtained from isolated myelin, it was found that several microtubule associated proteins (MAPs), particularly the stable tubule only peptide (STOP) and MAP 1B, as well as actin and tubulin were markedly increased. In the present paper, we compare the changes in expression of brain and myelin cytoskeletal proteins in a newly generated transferrin transgenic mouse (Tg), overexpressing the human transferrin gene, with the results obtained in aTf-injected rats. In the myelin cytoskeletal fraction of Tg mice there was a significant increase in the expression of MBP, tubulin, tau and STOP, similarly to what was previously found in the aTf-injected rats. Immunohistochemical studies showed that a variance with what occurs in the aTf-injected model, in which the above mentioned changes were limited to the corpus callosum, in the Tg mice the changes in expression of cytoskeletal proteins were observed in the various anatomical areas studied such as cerebral cortex, brain stem and cerebellum. There was also an increased expression of neurofilaments in the Tg animals, in contrast with results obtained in aTf-injected rats, suggesting that in the Tg mice, the continuous overexpression of Tf might also induce some neuronal changes. Changes in tau, total and acetylated tubulin and MAP 1B were observed in both neurons and OLGc. The increase in STOP was more significant in OLGc while the changes in MAP2 were exclusively found in neurons.