bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pentoxifylline Synergizes with All-Trans Retinoic Acid to Induce Differentiation of HL-60 Myelocytic Cells, but Suppresses tRA-Augmented Clonal Growth of Normal CFU-GM
Authors: Yang K.D. , Chao C.Y. , Shaio M.F. 
Published: April 2003

All-trans retinoic acid (tRA) has been shown to promote terminal differentiation of promyelocytic leukemia cells, but frequently induce hyperleukocytosis and pulmonary leakage syndrome. Employing pentoxifylline (PTX), a phosphodiesterase inhibitor which could raise intracellular cAMP and modulate leukocyte activation, we sought to investigate if PTX could enhance tRA-induced promyelocytic leukemic cell differentiation but suppress tRA-augmented growth and activation of human granulocytes. tRA could significantly suppress clonal growth of U937 and HL-60 leukemic cells but enhanced the CFU-GM formation of normal bone marrow cells (22 ± 6 vs. 90 ± 16 CFU/well). PTX significantly augmented tRA suppression of clonal growth of U937 and HL-60 leukemic cells but suppressed tRA-augmented CFU-GM formation of normal bone marrow cells (90 ± 16 vs. 25 ± 9 CFU/well). In addition, PTX enhanced tRA-induced growth inhibition and differentiation of promyelocytic HL-60 leukemic cells, but suppressed respiratory burst activation by the immature granulocytic HL-60 cells and suppressed CD11b adhesion molecule expression by mature granulocytes. PTX similar to dibutyric cAMP promoted HL-60 myelocytic leukemic cell differentiation and growth inhibition, whereas PTX, in contrast to dibutyric cAMP which could augment phorbol myristate acetate (PMA)-elicited respiratory burst activity by immature granulocytes, suppressed the PMA-elicited respiratory burst activity by immature and mature granulocytes. PTX did not raise the intracellular cAMP level of HL-60 cells, but partly suppressed the dibutyric cAMP-elicited elevation of intracellular cAMP level. Results from these studies suggest that PTX might act through different signaling pathways to enhance tRA-induced myelocytic leukemic cell differentiation but prevent from hyperreactive normal granulopoiesis and granulocyte activation.
Continuous Interleukin-2 Infusion Combined with Cyclophosphamide- Based Combination Chemotherapy in the Treatment of Hemato-Oncological Malignancies
Authors: Nagler A. , Ackerstein A. , Ben-Shahar M. , Or R. , Naparstek E. , Ben-Yosef R. , Slavin S. 
Published: April 2003

The combination of a cyclophosphamide (CTX)-based chemotherapy regimen and interleukin-2 (IL-2) has been shown to provide synergistic effects against malignancy in animal models. We therefore conducted a phase I–II trial combining CTX-based combination chemotherapy or CTX alone with high-dose IL-2 in patients with advanced and refractory malignant disease. Fifteen patients with hemato-oncological malignancies (malignant lymphoma 8, multiple myeloma 3, solid tumor 2, leukemia 2) were enrolled in the study. Continuous high-dose IL-2 infusion was shown to be safely administered, starting as soon as recovery of white blood cell count. All patients developed rebound lymphocytosis 24–48 h after termination of IL-2 infusion. Although grade IV toxicity was observed in 5 patients (7 episodes), all side effects completely subsided. Triple chemotherapy (CTX, etoposide and Ara-C) seemed rather toxic (in this group of heavily treated patients) while CTX alone was well tolerated. Four out of 13 (31%) evaluable patients had partial response and another patient (7%) had stabilization of disease progression lasting 2–8 months. Our conclusion is that the combination of CTX and continuous infusion of IL-2 is feasible and should be investigated in patients with various malignant neoplasms.
Efficacy and Side Effects of Deferiprone (L1) in Thalassemia Patients Not Compliant with Desferrioxamine
Authors: Taher A. , Chamoun F.M. , Koussa S. , Saad M. Abi , Khoriaty A.I. , Neeman R. , Mourad F.H. 
Published: April 2003

We report our experience with deferiprone (L1) (DFP) in 17 thalassemic patients, followed up in one center in Lebanon, who were initially on desferrioxamine and then shifted to DFP at a dose of 50–75 mg/kg/day as the sole chelator during 1-year follow-up. All 17 patients were compliant with therapy and there was no change in physical examination over the study period. Eight patients (47.1%) were positive for hepatitis C virus (HCV) antibodies. Urinary iron excretion was 21.8 ± 14 mg/24 h (mean ± SD) 1 week after starting DFP and dropped 12 months later to 13 ± 7.4 mg/24 h (p = 0.009, paired t test). The initial serum ferritin level was 3,863 ± 2,344 μg/l which dropped to 3,179 ± 2,075 at 12 months after starting therapy (p = 0.07). HCV-negative patients as a group exhibited a significant decrease in serum ferritin after 6 and 12 months of DFP therapy (3,942 ± 2,739 vs. 2,341 ± 1,179 and 2,681 ± 1,519 μg/l; p < 0.03 and p < 0.05, respectively). The most frequent side effects were joint pain, stiffness or swelling in 6 patients (35.3%), and nausea in 7 patients (41.2%), but these were well tolerated and did not require stopping treatment.
Sequential Use of Deferiprone and Desferrioxamine in Primary School Children with Thalassaemia major in Turkey
Authors: Aydinok Y. , Nisli G. , Kavakli K. , Coker C. , Kantar M. , Çetingül N. 
Published: April 2003

The effectiveness of the sequential use of deferiprone and desferrioxamine (DFO) in children with thalassaemia major was examined. Seven thalassaemic children in whom urinary iron induced by deferiprone was sufficient to maintain a negative iron balance were enrolled in the long-term trial. Deferiprone at a dose of 75 mg/kd/day in 3 divided doses was given for 4 school days a week. The group was given DFO at a dose of 40–50 mg/kg/day s.c. over 8–12 h with a battery-operated pump for 2 days at the weekend. In addition to the safety variables, they were monitored for serum ferritin levels at 2-month intervals and hepatic iron concentrations in liver tissues were determined at the beginning and the 6th month of therapy. The severity of hepatic damage was graded according to the Knodell hepatic activity index and the fibrosis was quantified. None of the patients suffered adverse effects of the therapy but a transient increase in serum ALT levels was noted. A nonsignificant decline in serum ferritin was observed (p = 0.08), a significant reduction in hepatic iron concentration was also determined (p = 0.03). The hepatic activity index in liver tissues of the patients at the 6th month of the sequential therapy significantly decreased (p = 0.03) whereas fibrosis scores did not differ significantly (p = 0.25).
Possible Association between Cytomegalovirus Infection and Gastrointestinal Bleeding in Hemophiliac Patients
Authors: Nogueira Eliana , Arruda Valder R. , Annicchino Bizzacchi Joyce M. , Costa Fernando F. , Castro Ozelo Margareth , Lúcio Rossi Claudio , Costa Sandra C.B. 
Published: April 2003

Cytomegalovirus (CMV) infection is of major concern in immunocompromised and immunosuppressed patients. Prior to the introduction of HIV-1 antibody screening and efficient virucidal processes to inactivate viruses, individuals with a factor VIII or factor IX deficiency had a high risk of contracting HIV-1 infection through the infusion of contaminated blood products. In addition, blood products were also frequently associated with alterations in immune function. This study investigated the frequency of active CMV infection and its clinical relevance in Brazilian hemophiliacs. One hundred hemophiliacs were screened for the presence of CMV-DNA in their blood using nested PCR. Twenty-five out of 100 patients (25%) were positive for CMV-DNA and 24 of these 100 patients (24%) were HIV-1 positive; 6 of these 24 (25%) were positive for CMV-DNA. A similar frequency was observed among HIV-1-negative patients. In 60 hemophiliacs, the clinical relevance of the CMV infection was assessed. Twenty-one patients were positive for CMV-DNA. Of these, 10 had gastrointestinal bleeding compared to only 9 of 39 patients who were CMV-DNA negative (p = 0.05; χ<sup>2</sup> test). These data indicate a high prevalence of active CMV infection in Brazilian hemophiliac patients, irrespective of whether the patients were or were not infected by HIV-1. There was a possible association between the presence of CMV and the occurrence of gastrointestinal bleeding.
Stress Response in a Leporine Renal Cell Model
Authors: Henle Kurt J. , Jethmalani Sunita M. , Nolen Greg T. , Wang Sho-Ya , Nowak Grazyna , Schnellmann Rick G. 
Published: April 2003

It is well established that renal proximal tubule (RPT) cells grown under standard in vitro conditions attenuate many of their in vivo properties and functions. Thus, the study of renal stress response mechanisms requires an appropriate cell culture model. In the present study, we compared the heat stress (10 min, 45°C) response of freshly isolated RPT cells with that of RPT cells grown in vitro for 6 days under two different culture conditions: (1) SHAKE conditions, where oxygen levels and physiological functions are maintained via continuous media motion [Nowak G, Schnellmann RG: Am J Physiol 1996;271:C2072–2080] and (2) STILL conditions, involving standard cell culture which leads to partial hypoxia and a marked reduction in physiological functions. The freshly isolated RPT cells progressively synthesized heat shock proteins (HSPs) and stress glycoproteins (SGs) during a 3-hour culture period in vitro. Under these conditions, heat stress did not further increase HSP and SG synthesis. In RPT cells grown under SHAKE conditions, HSP70 synthesis was detected 1 h after heat stress and decreased below detection by 3 h. In contrast, the uptake of radiolabeled mannose into (glycoprotein) GP62 (M<sub>r</sub> 62,000), GP50, and GP38 was observed in control SHAKE cultures and was not further increased after heat stress. These results are consistent with immunohistochemistry studies, where similar changes in HSP70 and GP50 expression were noted. RPT cells grown under STILL conditions showed both increased synthesis of HSP70 and increased glycosylation of GP62, GP50, and GP38 as early as 1 h after heat stress, but in contrast to SHAKE conditions, this heat-induced stress response further intensified at 3 h after heat stress. By 7 h after heating, HSP synthesis returned to control levels, while glycosylation of GP62 and GP50 remained elevated. Based on our results, we conclude that freshly isolated RPT cells exhibit a stress response that may be caused by acute cell isolation/culture stress. While this stress response unfolds, freshly isolated RPT cells appear unable to respond to additional heat stress. RPT cells grown under SHAKE and STILL conditions exhibit high rates of SG glycosylation, especially that of GP62, possibly reflecting a ‘stress’ condition associated with growth on plastic substrate. Concurrently, RPT cells from STILL cultures show a higher capacity for responding to acute heat stress than SHAKE cultures, evidenced by the transiently increased HSP synthetic rates. The interpretation of the renal stress response capacity, therefore, must be linked to a specific culture condition.
Potassium Depletion Stimulates mRNA Expression of Proximal Tubule AT<sub>1</sub> Angiotensin II Receptors
Authors: Burns Kevin D. , Smith Iain B. 
Published: April 2003

Dietary potassium (K<sup>+</sup>) deficiency is associated with blood pressure elevation and impaired urinary sodium excretion. Since angiotensin II is a potent stimulator of tubular sodium transport, we studied the effect of low [K<sup>+</sup>] on expression of kidney AT<sub>1</sub> angiotensin receptors. In rabbits fed a K<sup>+</sup>-deficient diet for 14 days, plasma [K<sup>+</sup>] was significantly reduced compared to rabbits fed a standard diet (control: 4.06 ± 0.12 vs. K<sup>+</sup>-deficient: 2.66 ± 0.19 mmol/l; p < 0.001; n = 6–9). By Northern hybridization or RNase protection assays, dietary K<sup>+</sup> deficiency caused an increase in mRNA expression for AT<sub>1</sub> receptors in kidney cortex (43.5 ± 12.9% increase vs. control; p < 0.04; n = 8), and in proximal tubule segments in suspension (76.4 ± 28.8% increase vs. control; p < 0.005; n = 6). K<sup>+</sup> deficiency had no effect on AT<sub>1</sub> receptor mRNA expression in liver, or on mRNA expression of β-actin in kidney cortex, proximal tubule suspensions, or liver. To determine if low extracellular [K<sup>+</sup>] might directly modulate AT<sub>1</sub> receptor mRNA expression, primary cultures of rabbit proximal tubule cells were incubated for 1, 3, 6 or 24 h in media with or without 5 mmol/l K<sup>+</sup>. Incubation of cells in 0 mmol/l K<sup>+</sup> caused a 99.2 ± 32.9% increase in AT<sub>1</sub> receptor mRNA expression at 3 h (p < 0.001; n = 14), returning to control levels by 24 h. Incubation of proximal tubule cells in 0 mmol/l K<sup>+</sup> also caused a significant increase in basolateral membrane specific binding of [<sup>125</sup>I]-angiotensin II (p < 0.05; n = 4). These results indicate that dietary K<sup>+</sup> deficiency and low extracellular [K<sup>+</sup>] stimulate expression of kidney AT<sub>1</sub> angiotensin II receptors. Increased AT<sub>1</sub> receptor mRNA and protein expression in proximal tubule may promote enhanced sodium reabsorption in K<sup>+</sup> deficiency.
Biosynthesis of Methylguanidine in the Hepatic Peroxisomes and the Effect of the Induction of Peroxisomal Enzymes by Clofibrate
Authors: Takemura Katsumi , Aoyagi Kazumasa , Nagase Sohji , Gotoh Michihiro , Hirayama Aki , Ueda Atsushi , Tomida Chie , Koyama Akio 
Published: April 2003

A state of peroxidation is one of the factors contributing to uremia. For example, we have reported that certain species of reactive oxygen, particularly the hydroxyl radical, play an important role in the biosynthesis of methylguanidine which contributes to toxicity in patients with uremia. However, it is uncertain which enzymes are involved in the synthesis of methylguanidine from creatinine. In this study, we attempt to show methylguanidine synthesis in the presence of peroxisomal enzymes that catalyze the β-oxidation of fatty acids. In addition, we investigate the effect of clofibrate, which induces peroxisomal enzymes or glutathione peroxidase activity, on methylguanidine synthesis in the peroxisomal fraction. Male Wistar rats were fed with the chow containing 0.5% clofibrate to induce peroxisomal enzymes and control rats were fed with ordinary laboratory chow. Peroxisomal fractions were obtained from liver homogenates by centrifugation, and incubated with creatinine in 0.1 <i>M</i> potassium phosphate buffer pH 7.4 at 37°C. Results show that methylguanidine is synthesized from creatinine concomitant with the synthesis of hydrogen peroxide from endogenous substrates in the peroxisomal fraction. This methylguanidine synthesis is inhibited by the addition of dimethylsulfoxide, glutathione, or sodium azide (p < 0.01). The rate of methylguanidine synthesis in clofibrate-treated rats was significantly less than that in control rats (p < 0.02). These results suggest that methylguanidine is synthesized in the peroxisomal fraction, and reactive oxygen species which are generated through this enzymatic reaction, participate in methylguanidine synthesis. Moreover, the induction of a scavenger system, especially glutathione peroxidase takes precedent over the generation of reactive oxygen species in peroxisomes treated with clofibrate.
Urea Reduction Ratio Considering Urea Rebound
Authors: Maduell F. , Garcia-Valdecasas J. , Garcia H. , Hdez-Jaras J. , Sigüenza F. , del Pozo C. , Giner R. , Moll R. , Garrigos E. 
Published: April 2003

An American National Study shows that survival benefits from higher dialysis doses appear to be present up to a Kt/V level of 1.3 or a urea reduction ratio (URR) of 70%. The effect of increasing dialysis efficiency magnified urea rebound and the error in URR determinations. Several formulas have been developed to calculate URR considering the urea rebound (URRr). Smye and coworkers have proposed a method whereby the equilibrated blood urea nitrogen is predicted by additional intradialytic urea sample. Maduell and colleagues, based on analysis of postdialysis urea rebound, have proposed a method whereby the urea rebound is predicted. To compare measured URRr to estimated by Smye and Maduell formulas, 384 patients were studied, 211 males and 173 females, who received a dialysis session with their habitual parameters. Measurements of plasma urea concentration were obtained at the beginning, 90–100 min following the start of dialysis, at the end, and 45 min after dialysis. The postdialysis urea rebound was 22.4 ± 9.7%. The urea kinetic model Kt/V was 1.365 ± 0.26, and Kt/Vr was 1.14 ± 0.23. URR was 68.7 ± 6.6%, and when it was calculated with urea rebound, it decreased to 61.9 ± 7.4%. The URRr correlated with calculations by Smye and Maduell formulas: 60.7 ± 8.4 (r = 0.722, p < 0.001) and 61.8 ± 6.6 (r = 0.933, p < 0.001), respectively. The precision of estimated limits of agreement and percentage of error by Bland and Altman analysis show that URRr estimated Maduell formula could be used in place of the URRr. Otherwise, the degree of agreement of the Smye method was not clinically acceptable. In conclusion, our results led us to suggest that in actual dialysis, the use of URR is not adequate for delivered hemodialysis dose, and URRr should be used. URRr estimated by Maduell formula could be a simple and accurate method for use in clinical practice. The recommended dialysis dose by the American National Study of URR of 70% could correspond, considering urea rebound, to Kt/Vr 1.18 or URRr of 64%.
Dipyridamole Inhibits Human Mesangial Cell Proliferation
Authors: Hillis Graham S. , Duthie Lesley A. , MacLeod Alison M. 
Published: April 2003

<b>Background:</b> Many glomerular diseases are associated with mesangial cell proliferation and the accumulation of extracellular matrix. At present, there are, however, few treatments which can inhibit these processes. The current study assessed the effects of the anti-platelet and putative anti-proliferative drug dipyridamole (DP) on the growth of human mesangial cells in vitro and their production of the extracellular matrix protein, fibronectin. <b>Methods:</b> Human mesangial cell proliferation, both intrinsic and stimulated by platelet-derived growth factor, was assessed using <sup>3</sup>H-thymidine incorporation and an MTT proliferation assay. A sandwich enzyme-linked immunosorbent assay was used to study the effects of DP on fibronectin synthesis, again in cells stimulated by transforming growth factor beta 1 and in unstimulated cells. <b>Results:</b> At concentrations compatible with the serum levels found in subjects consuming standard dosages, DP significantly inhibited the growth of human mesangial cells in vitro in a dose-dependent fashion. DP also abrogated the mitogenic effects of platelet-derived growth factor. It had no significant effects on the synthesis of fibronectin by these cells (either spontaneous or induced by transforming growth factor beta 1). There was no evidence of cytotoxicity. <b>Conclusion:</b> These data suggest that DP may have a therapeutic role in proliferative glomerulonephritis and possibly other diseases characterized by cell proliferation.
The Proliferative Responsiveness of Mesangial Cells to Postnephrectomy Serum Declines Progressively with Time Elapsing after Contralateral Nephrectomy
Authors: Weissgarten J. , Modai D. , Cohn M. , Berman S. , Averbukh Z. 
Published: April 2003

Postnephrectomy serum has been proved to enhance proliferation of mesangial cells in culture. Studies in offspring to uninephrectomized (UNx) mothers indicate that it remains active for a long period following UNx. On the other hand, postnephrectomy renal compensatory growth in vivo is known to be completed within a short period. In this study we assessed the proliferative responses of mesangial cells from single kidneys of rats which were cultured 48 h or 4 months following contralateral nephrectomy. The proliferative stimulus was provided by different postnephrectomy sera. Proliferation of both experimental cell populations was significantly greater than that of controls. Moreover, the proliferation rate of early postcontralateral nephrectomy mesangial cells was greater than those harvested 4 months after nephrectomy. We, therefore, propose that the early in vivo completion of single kidney compensatory hypertrophy, at least in part, is due to progressive blunting of renal cell responsiveness to the mitotic stimulus of the animal’s serum.
High-Fiber Diets May Be Responsible for Hypomagnesaemia in Diabetic Patients
Authors: Mullis Primus-E. , Bianchetti Mario G. 
Published: April 2003

Dietary fibre is a subject of considerable recent interest, not only with respect to diabetic diets. Water-insoluble fibres may be beneficial in treating or preventing several gastrointestinal disorders, including colon cancer, and large amounts of water-soluble fibres have a positive effect on serum lipids and may delay glucose absorption without inducing malabsorption. Therefore daily consumption of a diet containing 20–35 g (15 g/1,000 kcal) dietary fibre from a wide variety of food sources is recommended [1].
Urinary Soluble HLA Class I Antigen in Patients with Minimal Change Disease: A Predictor of Steroid Response
Authors: Park Cheol Whee , Song Ho Chul , Shin Young Sin , Ahn Suk Joo , Kim Yong Soo , Kim Suk Young , Choi Eui Jin , Chang Yoon Sik , Bang Byung Kee 
Published: April 2003

In primary minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), increased lymphocyte reactivity to renal antigens has been defined. Soluble HLA class I antigen (sHLA-I) is actively secreted by T and B lymphocytes when they are stimulated by mitogens, antigens and lymphokines. To determine if serum and urine sHLA-I levels could predict steroid response in patients with MCD and differentiate those from FSGS, we have investigated 45 healthy controls, biopsy-proven 17 patients with MCD (edema and 24-hour urine protein >3.5 g/day), 8 patients with FSGS (24-hour urine protein >1 g/day) and 10 patients with membranous nephropathy (MGN) (24-hour urine protein >1 g/day). Before and after prednisone therapy (1 mg/kg/day or 2 mg/kg/EOD for 8 weeks), the levels of serum and urinary sHLA-I were measured by ELISA (sHLA-STAT; Sangstat Co., Calif., USA). After 8 weeks of treatment, 10 patients with MCD were responders (MCD-CR) while the other 7 patients with MCD were nonresponders (MCD-NR). Three of 7 patients with MCD-NR were re-biopsied and finally diagnosed as FSGS. They were included in the data of patients with FSGS. In healthy controls, serum sHLA-I was detected (415 ± 256 ng/ml), but urinary sHLA-I was not. At entry, there were no differences in age, sex, serum Cr and 24-hour urine protein among the patients with MCD-CR, MCD-NR and FSGS, but serum albumin was significantly elevated in patients with FSGS and MGN (p < 0.05). Serum sHLA-I levels were notably elevated in MCD-CR (1,040 ± 1,066 ng/ml), in MCD-NR (668 ± 315 ng/ml) and in FSGS (713 ± 790 ng/ml), but not in patients with MGN (444 ± 86 ng/ml) when compared with controls (p < 0.05). On the other hand, urinary sHLA-I levels in MCD-NR (541 ± 239 ng/mg Cr) and in FSGS (457 ± 239 ng/mg Cr) were significantly higher than those in MGN (125 ± 28 ng/mg Cr) and in MCD-CR (100 ± 42 ng/mg Cr, p < 0.05) and these substantial differences were maintained for 8 weeks. In all patients, serum and urinary sHLA-I levels were not reduced during 8 weeks of steroid therapy. We conclude that elevated serum and urinary sHLA-I levels reflect increased cellular immune response and disease activity in patients with MCD and FSGS. In patients with MCD, urinary sHLA-I may be an easily measurable indicator of predicting steroid response, while MCD-NR with high urinary sHLA-I levels might be re-evaluated for the possibility of FSGS.