bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reciprocal Functions of Liver Tumor Cells and Endothelial Cells
Authors: Okamoto H. , Ohigashi H. , Nakamori S. , Ishikawa O. , Imaoka S. , Mukai M. , Kusama T. , Fujii H. , Matsumoto Y. , Akedo H. 
Published: April 2003

<i>Background:</i> The mechanism by which tumor cells interact with endothelial cells at the primary site in metastasis remains obscure. <i>Materials and Methods:</i> To disclose the precise mechanisms and processes of metastasis and angiogenesis, we investigated the interactions of endothelial cells (CPAE; calf pulmonary arterial endothelial cells) with two mouse liver tumor cell lines, G-5, a highly metastatic clone, and G-1, a poorly metastatic clone, based on the difference in their angiogenic activities in vivo at a primary site. <i>Results:</i> G-5 cell cultured conditioned medium (CM) promoted migration of endothelial cells more than did G-1 cell CM, in migration assay using modified Boyden chambers. Anti-basic FGF antibody inhibited G-5-induced endothelial cell migration. Furthermore, endothelial cells stimulated proliferation of G-5 cells more than that of G-1 cells in coculture assay using Transwell chambers (pore size; 0.4 µm). Pretreated endothelial cells with bFGF enhanced tumor cell proliferation, suggesting the ability of activated endothelial cells to support tumor growth. In addition, incubation with endothelial cell CM also improved the proliferative activity of G-5 cells more than that of G-1 cells in a concentration-dependent fashion, indicating production and secretion of liver tumor cell growth substance by endothelial cells. <i>Conclusion:</i> These results provide evidence that liver tumor cells stimulate endothelial cell migration and migrated endothelial cells facilitate liver tumor cell proliferation. Tumor growth at a primary site may initially be dependent on migrated endothelial cells rather than vascularization or blood nutrient supply. This bi-directional paracrine relationship between liver tumor cells and endothelial cells may influence their metastatic ability.
Molecular Mechanisms by Which Iron Induces Nitric Oxide Synthesis in Cultured Proximal Tubule Cells
Authors: Chen Liguang , Wang Yiping , Kairaitis Lukas K. , Wang Yang , Zhang Bao-Hong , Harris David C.H. 
Published: April 2003

Nitric oxide (NO) levels are increased after exposure of cultured proximal tubule cells (PTC) to non-haem iron, potentially contributing to PTC injury in disease states associated with increased iron exposure, including proteinuric renal disease. The mechanisms underlying this observed increase were investigated. After 3 h exposure to 400 µ<i>M</i> nitrilotriacetate (NTA)-Fe, inducible nitric oxide synthase (iNOS) mRNA expression was significantly increased, with a corresponding increase in iNOS protein after 12 h. The nuclear binding activity of NFĸB with 400 µ<i>M</i> NTA-Fe was increased, and pyrrolidine dithiocarbamate (PDTC), an antioxidant inhibitor of NFĸB, prevented both activation of NFĸB and NO production in response to NTA-Fe. Inhibition of protein tyrosine kinase reduced iNOS mRNA, iNOS protein levels and NO production in response to NTA-Fe. The effect of tyrosine kinase inhibition on NFĸB activation was variable, with herbimycin but not genistein having an inhibitory effect. Activation of either protein kinase A or C increased iNOS mRNA and protein levels, and NO production in response to NTA-Fe, whereas only the protein kinase C activator phorbol dibutyrate (PDBu) had a stimulatory effect on NFĸB activation. The protein kinase A activator forskolin did not alter iron-induced activation of NFĸB. These data suggest that the observed increase in NO production by PTC in response to iron is due to increased transcription of iNOS. The transcriptional regulation of this response is complex and involves NFĸB, protein tyrosine kinase and the protein kinases A and C.
Apoptosis Induced by Serum Withdrawal in Human Mesangial Cells
Authors: Verzola Daniela , Villaggio Barbara , Berruti Valeria , Gandolfo Maria Teresa , Deferrari Giacomo , Garibotto Giacomo 
Published: April 2003

Apoptosis has been reported to occur both during the course of kidney development and the progression of kidney injury to scarring. Insulin-like growth factor binding protein-3 (IGFBP-3), a component of the IGF system, has been shown to induce apoptosis in cancer cell lines. However, if IGFBP-3 has similar effects in human mesangial cells (HMC) remains unknown. The purpose of this study was to examine the expression of IGFBP-3 and its possible effect on the induction of apoptosis in HMC during serum deprivation. We have observed that IGFBP-3 accumulates progressively in HMC in which serum has been withdrawn. In these cells, an increase of IGFBP-3 is observed before the production of apoptosis suggesting a link between these phenomena. Furthermore, the addition of IGFBP-3 in physiological amounts (from 100 to 400 ng/ml) to culture medium devoid of growth factors accelerates and increases the apoptotic process with a dose-dependent effect. These findings suggest that IGFBP-3 is a mediator of cell death in human mesangial cells when the availability of growth factors is curtailed. These data also suggest that IGFBP-3 could contribute to apoptotic processes observed in human disease.
Renal Effects of Nabumetone, a COX-2 Antagonist: Impairment of Function in Isolated Perfused Rat Kidneys Contrasts with Preserved Renal Function in vivo
Authors: Reichman James , Cohen Shlomo , Goldfarb Marina , Shina Ahuva , Rosen Seymour , Brezis Mayer , Karmeli Fanny , Heyman Samuel N. 
Published: April 2003

The constitutive cyclooxygenase (COX)-1 enzyme has been considered the physiologically important isoform for prostaglandin synthesis in the normal kidney. It has, therefore, been suggested that selective inhibitors of the ‘inducible’ isoform (COX-2) may be free from renal adverse effects. We studied the renal effects of the predominantly COX-2 antagonist nabumetone in isolated perfused kidneys. As compared with controls, kidneys removed after in vivo administration of oral nabumetone (15 mg/kg) disclosed altered renal function with reduced glomerular filtration rate, filtration fraction, and urine volume and enhanced hypoxic outer medullary tubular damage. By contrast, renal function and morphology were not affected in vivo by nabumetone or its active metabolite 6-methoxy-2-naphthylacetic acid. The latter agent (10–20 mg/kg i.v.) did not significantly alter renal microcirculation, as opposed to a selective substantial reduction in medullary blood flow noted with the nonselective COX inhibitor indomethacin (5 mg/kg i.v.). In a rat model of acute renal failure, induced by concomitant administration of radiocontrast, nitric oxide synthase, and COX inhibitors, the decline in kidney function and the extent of hypoxic medullary damage with oral nabumetone (80 mg/kg) were comparable to a control group, and significantly less than those induced by indomethacin. In rats subjected to daily oral nabumetone for 3 consecutive weeks, renal function and morphology were preserved as well. Both nabumetone and 6-methoxy-2-naphthylacetic acid reduced renal parenchymal prostaglandin E<sub>2</sub> to the same extent as indomethacin. It is concluded that while nabumetone adversely affects renal function and may intensify hypoxic medullary damage ex vivo, rat kidneys are not affected by this agent in vivo, both in acute and chronic studies. COX selectivity may not explain the renal safety of nabumetone.
Altered Cultured Mesangial Cell Phenotypes from RF/J Mice: A Spontaneous Immune Complex Mediated Glomerulonephritis with Progressive Glomerulosclerosis
Authors: Yashiro Masatomo , Muso Eri , Kamata Tadashi , Oyama Atsushi , Sasayama Shigetake , Yoshida Haruyoshi 
Published: April 2003

<i>Background/Aim:</i> RF/J mice are a model of spontaneous immune complex mediated glomerulonephritis showing massive extracellular matrix accumulation and progressive glomerulosclerosis. The aim of this study was to investigate whether there is an altered cultured mesangial cell (MC) phenotype in RF/J mice associated with these glomerular changes. <i>Methods:</i> The nature of cultured MCs from RF/J mice in the proliferative response to platelet-derived growth factor (PDGF) BB was compared with that of normal mice (BALB/c) by <sup>3</sup>H-thymidine incorporation. The binding of PDGF-BB was examined with Scatchard analysis, and the messenger RNAs (mRNAs) of PDGF β-receptor, collagen I, collagen IV, and fibronectin were detected using Northern blot analysis in the MCs of each mouse. <i>Results: </i>The <sup>3</sup>H-thymidine incorporation of MCs from RF/J mice showed significantly lower responses to PDGF-BB stimulations with concentrations ranging from 0.5 to 10.0 ng/ml in comparison with those of BALB/c mice which exhibited a proportional dose- dependent increase of the incorporation (p < 0.05 for 0.5 ng/ml PDGF-BB, p < 0.01 for 1.0–10.0 ng/ml). According to the Scatchard analysis, MCs from BALB/c mice showed aKD of 105 p<i>M</i> of PDGF-BB binding to its receptors, and the density of receptors was 5.82 fmol/10<sup>5</sup> cells. However, no binding PDGF-BB site on the surface of MCs from RF/J mice was noted. Northern blot analysis of MCs from RF/J mice indicated negative expression of detectable PDGF-β receptor mRNA. As for matrix protein messages, MCs from RF/J mice did not express mRNA of type I collagen, but did express a higher amount of type IV collagen and fibronectin in comparison with MCs from normal BALB/c mice. <i>Conclusions:</i> An altered phenotype in MCs of RF/J mice was demonstrated, possibly contributing to the characteristic pathological glomerular changes. However, the precise association remains to be clarified.
Alleviating Constipation in the Elderly Improves Lower Urinary Tract Symptoms
Authors: Charach Gideon , Greenstein Alexander , Rabinovich Pavel , Groskopf Itamar , Weintraub Moshe 
Published: April 2003

<i>Background:</i> Constipation and lower urinary tract symptoms (LUTS) very frequently occur in the elderly, and several reports have suggested that dysfunction in either one of these systems may affect the other. Most studies correlating rectal and bladder dysfunction, however, have been carried out in children or young women. <i>Objective:</i> To examine the effect of alleviating constipation on LUTS in the elderly. <i>Methods:</i> Fifty-two patients aged 65–89 (mean 72 ± 13) years with chronic constipation and LUTS participated in this prospective cohort study. Before treatment of constipation was initiated and on their monthly visits, patients completed a questionnaire regarding their constipation pattern, urinary symptoms, sexual function and mood, and underwent urinalysis. Urinary tract anatomy and residual urine were evaluated by abdominal ultrasound at the commencement and completion of the study. Patients were followed up for 4 months. <i>Results:</i> Treatment of constipation increased the number of weekly defecations from 1.5 ± 0.9 to 4.7 ± 1.2 (p < 0.001). Patients spent less time on the toilet (25 ± 2.1 versus 63 ± 1.9 min, p < 0.0001). Fewer patients reported urgency (16 versus 34, p < 0.001), frequency (25 versus 47, p < 0.001) and burning sensation during urination (6 versus 17, p < 0.05). There was improvement in the scoring of urgency, frequency and burning sensation (from a baseline of 52 to 126, 131 and 95, respectively, p < 0.001). Urinary stream disturbances improved in 32 of the 52 patients (p < 0.001). Residual urine volume decreased from 85 ± 39.5 to 30 ± 22.56 ml (p < 0.001). There was also a significant decrease in the number of patients with bacteriurial events (5 versus 17, p < 0.001), and an improvement in sexual activity and mood (p < 0.05). <i>Conclusions:</i> Our data demonstrated that medical relief of constipation significantly improves LUTS in the elderly which, in turn, improves the patient’s mood, sexual activity and quality of life.
Suspected Cardiac Syncope in Elderly Patients: Use of the 12-Lead Electrocardiogram to Select Patients for Holter Monitoring
Authors: Manchanda S. , Ehsanullah M. 
Published: April 2003

<i>Background:</i> Results of 24-hour Holter monitoring in elderly patients are often unhelpful, since the prevalence of asymptomatic arrhythmias increases and their prognostic significance is unclear. We investigated the value of the resting electrocardiogram (ECG) in predicting significant findings on 24-hour Holter recordings in those suspected of having cardiac syncope. <i>Objective:</i> To see whether the resting 12-lead ECG can be used as a screening tool to select elderly patients suspected of having cardiac syncope for 24-hour ECG monitoring. <i>Method:</i> Comparison of resting 12-lead ECGs and 24-hour Holter tapes in 145 consecutive elderly outpatients suspected of having a cardiac cause for falls, dizziness, or syncope. <i>Results:</i> Four of 30 normal ECGs (13%) showed an abnormality on Holter monitoring as compared with 55 of the 115 abnormal ECGs (47.8%; chi = 11.7143, p < 0.005). In the ‘normal’ group the 4 abnormal Holter recordings all showed short runs of supraventricular tachycardia, and no intervention resulted. The 115 abnormal resting ECGs showed either ischaemia (n = 27), dysrhythmia (n = 28), sinus bradycardia (n = 22), or conduction defects (n = 38). The 55 of these which showed abnormalities on Holter recordings occurred mostly where the resting ECG showed dysrhythmia (n = 14/28; 50%), bradycardia (n = 19/22; 86.4%), and conduction defect (n = 17/38; 44.7%). Seven patients had complete heart block on Holter, and all had conduction defects on resting ECG (p < 0.0004). Fifteen patients had pauses of longer than 3 s on Holter; all had conduction defect, bradycardia, or dysrhythmias on resting ECG (p < 0.0045). Sixteen patients were paced because of complete heart block or pauses on Holter recordings, and all had either bradycardia or conduction defects on resting ECG, resulting in complete resolution of their symptoms. <i>Conclusions:</i> Patients with suspected cardiac syncope and normal resting ECGs are unlikely to reveal significant abnormalities on single 24-hour Holter monitoring. Cardiac event recorder or prolonged Holter monitoring may be required in patients with strong clinical history. Those with abnormal ECGs, in particular sinus bradycardia and conduction defects, are highly likely to have significant abnormalities on 24-hour ECG monitoring.
Natural Killer Activity and Thyroid Hormone Levels in Young and Elderly Persons
Authors: Kmieć Zbigniew , Myśliwska Jolanta , Rachoń Dominik , Kotlarz Grażyna , Sworczak Krzysztof , Myśliwski Andrzej 
Published: April 2003

<i>Background:</i> On the basis that (1) multiple interactions exist between the hormonal and immune systems, and (2) aging is accompanied by changes in thyroid hormone metabolism and responsiveness, we postulate that thyroid hormones may be involved in the observed decrease in natural killer (NK) activity in a population of apparently healthy elderly subjects. The purpose of the study is to compare NK cytotoxic activity and serum concentrations of TSH and thyroid hormones in healthy old and young people, and to assess in vitro the effects of triiodothyronine (T<sub>3</sub>) on NK activity. <i>Materials and Methods:</i> Sixteen of the 47 healthy old people (mean age 64 ± 5.2) were classified as optimally healthy, and the remainder as ‘almost healthy’ (according to the criteria of the Senieur protocol) [Ligthart et al., Mech Ageing Dev 1984;28:47–55]; the mean age of the healthy young people was 23.3 ± 2.3 years. NK cytotoxic activity of peripheral blood mononuclear cells was assessed using <sup>51</sup>Cr release from K562 target cells. The cutoff level for defining low and high NK responses was set at a value of 20%. Serum concentrations of TSH, total thyroxine (T<sub>4</sub>) and total triiodothyronine (T<sub>3</sub>) were measured by radioimmunoassay. <i>Results:</i> NK activity in the ‘optimally healthy’ elderly was high (mean 41 ± 12%, SE), whereas ‘almost healthy’ subjects showed low NK activity (mean 6 ± 5%). Serum T<sub>4</sub> and TSH levels, but not T<sub>3</sub> concentrations were similar in both the young and old. We observed a significant correlation (r = 0.53, n = 21, p < 0.05) between the serum total T<sub>3</sub> level and the NK activity in the elderly individuals. Under in vitro conditions exogenous T<sub>3</sub> significantly increased NK activity in the elderly subjects who had serum T<sub>3</sub> values at the lower end of the reference range. However, no effect of T<sub>3</sub> on NK activity was observed in peripheral blood mononuclear cells obtained from either old or young individuals who had serum T<sub>3</sub> levels at the midpoint of the range. <i>Conclusion:</i> Decreased serum concentrations of total T<sub>3</sub> may contribute to low NK activity in the ‘almost healthy’ subgroup of the elderly.
Assessing the Influence of Payment on Motivations of Women Participating as Oocyte Donors
Authors: Lindheim Steven R. , Chase Jennie , Sauer Mark V. 
Published: April 2003

We report on the motivations of potential ovum donors entering an assisted reproduction program and discuss the potential ramifications of escalating payments to donors. From July 1995 to July 1998, recruitment of ovum donors was directed at healthy women between 21 and 34 years of age. Financial remuneration for services rendered was USD 2,500 from July 1995 through March 1998 and increased to USD 5,000 after that. Donors were screened and consented according to established SART guidelines. The demographic background of the women was similar for women paid USD 2,500 to those receiving USD 5,000. The financial motivation was greater in those receiving USD 5,000 (68%) than USD 2,500 (39%). Some form of expressed altruism was similarly present in both groups (USD 5,000 90%, and USD 2,500 91%). However, altruism expressed as the sole motivation occurred more in those receiving USD 2,500 (61%) compared to USD 5,000 (32%). Financial reimbursement has escalated for the services of ovum donors in order to maintain the increasing demand. While money has become a dominant factor motivating ovum donors, its seductive nature requires even greater attention to adequate informed consent. Young donors may be unable to adequately weigh the risks of ovarian hyperstimulation and oocyte retrieval against the monetary reward.
Value of Subcutaneous Drainage System in Obese Females Undergoing Cesarean Section Using Pfannenstiel Incision
Authors: Al-Inany Hesham , Youssef Gamal , Abd ElMaguid Ahmed , Abdel Hamid Moustapha , Naguib Ahmed 
Published: April 2003

<i>Objective:</i> To determine whether closed subcutaneous drainage systems were efficacious in reducing the rate of wound breakdown of Pfannenstiel incision after cesarean section (CS) in obese females. <i>Design:</i> Prospective controlled clinical trial. <i>Participants:</i> 118 obese pregnant females with a body mass index >32 undergoing CS were divided into two groups: group I (n = 78) with closed subcutaneous drainage system and group II (n = 40) without drainage system. Incision closure technique was standardized. Prophylactic antibiotics were given routinely to both groups. <i>Outcome Measures:</i> Primary outcomes were the incidence of wound breakdown in both groups together with rate of hematoma formation and occurrence of fever. Secondary outcomes were amount of fluid drained, need for redressing. <i>Results:</i> Wound breakdown occurred in 9 cases in group I (11.5%), while it happened in 5 cases in group II (12.5%) (p > 0.05). Relative risk was 0.92 (95% CI 0.26–3.75). Hematoma formation was observed in only 1 case in the nondrainage group (group II). Fever was observed in 18 cases in group I (23.1%) in the first 24 h postoperative while in group II, 13 cases developed fever (32.5%) (p > 0.05). The need for redressing within the first 24 h was only in 2.5% of cases in group I while it was 17.9% in group II (p < 0.05). <i>Conclusion:</i> We found no significant benefit in using a subcutaneous drain as a prophylactic measure against wound breakdown in obese pregnant females undergoing CS as long as they received a prophylactic antibiotic.
Auxological and Endocrine Evolution of 28 Children with Prader-Willi Syndrome: Effect of GH Therapy in 14 Children
Authors: Tauber M. , Barbeau C. , Jouret B. , Pienkowski C. , Malzac P. , Moncla A. , Rochiccioli P. 
Published: April 2003

We report on the auxological and endocrine evolution of 28 patients presenting with Prader-Willi syndrome. Half of them received growth hormone (GH) therapy (group 2). The spontaneous auxological evolution was analyzed in the two groups from 2 to 8 years; the mean SDS for height remained stable (–0.6 ± 0.6) in group 1 and decreased (from –2.0 ± 0.9 to –2.7 ± 0.6) in group 2. Magnetic resonance imaging showed marked pituitary hypoplasia in the two groups. In group 2, the mean GH peak after two provocative tests was 3.8 ± 2.4 µg/l, the mean SDS values for insulin-like growth factor I levels were –2.0 ± 1.5 (range from –0.5 to –5.0). The mean duration of GH treatment was 3.6 ± 2.9 (range 1–9.3) years. 14 children completed 1 year of treatment. The two groups had opposite evolutions in ΔSDS for height (–0.8 ± 0.8 vs. +1.1 ± 0.8), for growth velocity (–1.9 ± 2.2 vs. +2.9 ± 2.7), and for Z score of the body mass index (+0.37 ± 1.3 vs. –0.14 ± 0.76; group 1 vs. group 2). This retrospective study shows that, in children with Prader-Willi syndrome and true GH deficiency, long-term GH therapy is effective in increasing growth velocity and in maintaining body mass index.
Effect of Excitatory Amino Acids on Serum TSH and Thyroid Hormone Levels in Freely Moving Rats
Authors: Alfonso M. , Durán R. , Arufe M.C. 
Published: April 2003

The actions of glutamate (L-Glu), and glutamate receptor agonists on serum thyroid hormones (T4 and T3) and TSH levels have been studied in conscious and freely moving adult male rats. The excitatory amino acids (EAA), L-Glu, N-methyl-<i>D</i>-aspartate (NMDA), kainic acid (KA) and domoic acid (Dom) were administered intraperitoneally. Blood samples were collected through a cannula implanted in the rats jugular 0–60 min after injection. Thyroid hormone concentrations were measured by enzyme immunoassay, and thyrotrophin (TSH) concentrations were determined by radioimmunoassay. The results showed that L-Glu (20 and 25 mg/kg) and NMDA (25 mg/kg) increased serum thyroxine (T4), triiodothyronine (T3) and TSH concentrations. Serum thyroid hormone levels increased 30 min after treatment, while serum TSH levels increased 5 min after i.p. administration, in both cases serum levels remained elevated during one hour. Injection of the non-NMDA glutamatergic agonists KA (30 mg/kg) and Dom (1 mg/kg) produced an increase in serum thyroid hormones and TSH levels. These results suggest the importance of EAAs in the regulation of hormone secretion from the pituitary-thyroid axis, as well as the importance of the NMDA and non-NMDA receptors in this stimulatory effect.