bluuebunny/crossref_metadata_2025 huggingface dataset:
Chymase Inhibitor Improves Dermatitis in NC/Nga Mice
Authors: Watanabe Naohiro , Tomimori Yoshiaki , Saito Kayo , Miura Kenju , Wada Adumi , Tsudzuki Masaoki , Fukuda Yoshiaki
Published: April 2003

Background: Mast cell chymase is thought to participate in allergic inflammation, but its precise role remains undetermined. Inbred NC/Nga mice develop skin lesions similar to atopic dermatitis (AD) when they grow up in a conventional environment. To elucidate the possible role of chymase in AD, we examined the effect of a chymase inhibitor on skin lesions of NC/Nga mice. Methods: NC/Nga mice were given the chymase inhibitor SUN-C8257 daily at 150 mg/kg/day with drinking water, and the severity of the dermatitis was evaluated on day 35 of the experiment. The role of chymase in dermatitis was further investigated in vitro and in vivo using recombinant mouse mast cell protease-4 (mMCP-4). Results: Administration of SUN-C8257 significantly reduced the clinical skin and histological score in NC/Nga mice. SUN-C8257 also inhibited the accumulation of inflammatory cells, such as eosinophils and mast cells, in the affected lesions in this model. mMCP-4 stimulated eosinophil migration in vitro, and intradermal injection of the enzyme resulted in a significant accumulation of inflammatory cells, including eosinophils, at the injection site. Thus amelioration of the skin lesions in NC/Nga mice by SUN-C8257 might be, at least in part, due to the suppression of cell infiltration in the lesions. Conclusions: Mast cell chymase may contribute to the pathogenesis of AD, and SUN-C8257 will be beneficial to the treatment of the skin disorder.
Inflammatory Cytokines and Lipopolysaccharide Induce Fas-Mediated Apoptosis in Renal Tubular Cells
Authors: Jo Sang Kyung , Cha Dae Ryong , Cho Won Yong , Kim Hyoung Kyu , Chang Kyung Hyun , Yun Su Young , Won Nam Hee
Published: April 2003

Background/Aims: Increased susceptibility of the kidney to acute renal failure (ARF) in the setting of sepsis even in the absence of systemic hypotension is well known. In the hypothesis that the proinflammatory cytokines and lipopolysaccharide (LPS) in gram-negative sepsis can directly cause renal tubular cell apoptosis via Fas- and caspase-mediated pathways, we examined apoptosis and Fas, Fas ligand, FADD expression, as well as PARP cleavage in cultured human proximal tubular cells under the cytokine and LPS-stimulated conditions. Methods: HK-2 cell, immortalized human proximal tubular cell lines, were treated with 5 and 30 ng/ml of tumor necrosis factor-α (TNF-α), 5 and 20 ng/ml of interleukin-1β (IL-1β) and 30 ng/ml LPS for 24 h. Fas expression was examined by RT-PCR and Fas ligand, Fas-associated protein with death domain (FADD) and poly ADP ribose polymerase (PARP) cleavage were examined by Western blot analysis. Apoptosis was assessed by flow cytometer using Annexin V-FITC and propidium iodide (PI) staining and also by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) methods. Results: Fas mRNA expression (ratio of Fas/L-19) increased in the TNF-α 5, 30 ng/ml and LPS treated group (p < 0.01, p < 0.01, p = 0.02), but there was no difference between the low- and high-dose TNF-α groups. Fas ligand protein expression did not increase in the low-dose TNF-α treated group, but it increased significantly in the high-dose TNF-α treated group (p< 0.01), IL-1β- and LPS-treated groups (p < 0.01, p = 0.01, p < 0.01, p = 0.02). The intracellular adaptor protein, FADD expression also increased significantly in the high-dose TNF-α- and IL-β-treated groups (p = 0.04, p = 0.04), but in the low-dose TNF-α and IL-β treated group, it did not show statistically significant differences. In the LPS group, FADD expression also showed an increased tendency, but it was not statistically significant (p = 0.09). Western blot for PARP, a DNA repair enzyme mainly cleaved by caspase 3, showed increased 89- and 24-kD PARP cleavage products in TNF-α, IL-1β and LPS treated cells. The degree of apoptosis examined by DNA fragmentation and translocation of membrane phosphatidyl serine significantly increased in cytokines and LPS treated groups. Conclusion: These results suggest that Fas- and caspase-mediated apoptosis of tubular cells by inflammatory cytokines and LPS can be one of the possible mechanisms of renal dysfunction in endotoxemia.
Expression of Bcl-2 and Bax in Hypokalemic Nephropathy in Rats
Authors: Kimura Toshiaki , Nishino Toshihiko , Maruyama Naoki , Hamano Kazumasa , Kubo Atsushi , Iwano Masayuki , Shiiki Hideo
Published: April 2003

Objectives: Potassium depletion results in hyperplasia of renal tubular and interstitial cells in humans and animals, and potassium repletion induces rapid regression of hyperplasia. Apoptosis participates importantly in this reduction of cell number, although we have observed tubular and interstitial apoptosis in rats during potassium depletion as well. Methods: To investigate mechanisms of apoptosis in this model, we assessed expression of Bcl-2 and Bax, using immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Cell proliferation identifiable by labeling with 5-bromo 2′-deoxyuridine was prominent in tubular and interstitial cells of the cortex and outer medulla (OM) 7 days after potassium depletion. Simultaneously present apoptotic cells identified by light microscopy, electron microscopy, and nick end labeling were located mainly in the OM. Seven days after potassium repletion, apoptotic cells increased again but proliferating cells decreased. Bcl-2 protein distributed in the tubules of the OM was significantly decreased in potassium-depleted and potassium-repleted rats compared with control rats, while immunoreactivity for Bax protein tended to increase above control levels in potassium-depleted rats. RT-PCR for bcl-2 and bax demonstrated a significant decrease in levels of bcl-2 mRNA in potassium-depleted and potassium-repleted rats relative to those in controls. Expression of bax mRNA in potassium-depleted and potassium-repleted rats tended to increase, while ratios of bcl-2 mRNA to bax mRNA significantly decreased. Conclusions: These results suggest that apoptosis is associated with progression and regression of cellular proliferation in hypokalemic nephropathy, and a decrease in Bcl-2 may be involved in promoting this apoptotic process.
Tumor Removal Enhances Immunity Induced by B7.1
Authors: Lee Min-Jung , Choi Sang-Hoon , Shim Yhong-Hee , Cho Sun-Hee , Kim Chul-Woo
Published: April 2003

Costimulation of tumor T cells by B7.1 has been shown to be important for eliciting cell-mediated anti-tumor immunity. We constructed a stable B7.1 gene transfectant of a poorly immunogenic murine sarcoma, Moloney murine sarcoma virus-induced tumor cell line (MMSV). This transfectant, MMSV-B7.1, failed to produce any tumor development in syngeneic mouse models. When MMSV-B7.1 was simultaneously injected with wild-type MMSV, about half of the coinjected mice remained tumor free and displayed an increase in T cell population, upregulation of the mRNA level of various cytokines such as IL-4, IL-5, IL-10, IL-13, IL-15 and IFN-γ, and complete rejection of reinjected MMSV. To investigate whether MMSV-B7.1 demonstrates any vaccinal effect, the transfectant was injected following the surgical removal of the primary tumor mass. Following a re-challenge with wild-type MMSV, all vaccinated mice maintained their tumor free status and displayed a rapid recovery of down-regulated cytokine levels. The results suggest that B7.1 vaccination after tumor removal might be useful for the prevention of tumor recurrence.
Effects of Quinine and Quinidine on the Transient Outward and on the L-Type Ca2+ Current in Rat Ventricular Cardiomyocytes
Authors: Michel Delia , Wegener Jörg W. , Nawrath Hermann
Published: April 2003

The effects of the enantiomers quinine and quinidine on the transient outward current (Ito) and on the L-type Ca2+ current (ICa) were investigated in rat ventricular cardiomyocytes using the patch-clamp technique. At a stimulation frequency of 2 Hz, both quinine and quinidine depressed the magnitude of Ito and ICa; the half-maximal effects on Ito were achieved at 11 and 15 µmol/l, respectively, and those on ICa at 14 and 10 µmol/l, respectively. At 0.2 Hz, both drugs depressed the magnitude of Ito, but not that of ICa. A change in extracellular pH from 7.3 to 8.3 did not significantly influence the effects of the drugs (which are protonated to 98% at pH 7.3) on Ito or ICa. It is concluded that neither the different chemical structure nor the amount of protonation of quinine and quinidine controls their effects on Ito or ICa.
Neurotransmitter Mechanisms in Gabapentin Antinociception
Authors: Dixit R.K. , Bhargava V.K.
Published: April 2003

The present study was done to investigate the neurotransmitter mechanisms involved in gabapentin antinociception in healthy albino rats. The formalin test was used to asses antinociception. Gabapentin (10–120 mg/kg s.c.) decreased the pain score in the formalin test. In order to study the putative neurotransmitter mechanisms involved in gabapentin action, the effect of gabapentin (30 mg/kg s.c.) alone and in rats pretreated with different receptor blockers, e.g. bicuculine, saclofen, naloxone, mecamylamine, atropine, DL-p-chlorophenylalanine methyl ester hydrochloride, glibenclamide, theophylline, and L-arginine was assessed. Gabapentin decreased the pain score, and the ED50 of gabapentin was 36.8 ± 8.2 (30.2–43.1) mg/kg s.c. Pretreatment with different receptor blockers did not modify gabapentin (30 mg/kg s.c.) antinociception except for L-arginine which increased the pain score from 1.68 ± 0.29 (gabapentin) to 2.29 ± 0.41. Results suggest the involvement of L-arginine nitric oxide pathways in gabapentin antinociception.
Deoxycholic Acid Conjugates Are Muscarinic Cholinergic Receptor Antagonists
Authors: Raufman Jean-Pierre , Chen Ying , Zimniak Piotr , Cheng Kunrong
Published: April 2003

In the course of examining the actions of major human bile acids on cholinergic receptors, we discovered that conjugates of lithocholic acid are partial muscarinic agonists. In the present communication, we report that conjugates of deoxycholic acid (DC) act as cholinergic muscarinic receptor antagonists. Chinese hamster ovary (CHO) cells expressing rat M3-muscarinic receptors were used to test bile acids for inhibition of radioligand [N- 3H-methylscopolamine (3H-NMS)] binding; alteration of inositol phosphate (IP) formation; mitogen-activated protein (MAP) kinase phosphorylation and cell toxicity. We observed approximately 18.8, 30.3 and 37.1% inhibition of 3H-NMS binding with DC and its glycine (DCG) and taurine (DCT) conjugates, respectively (all 100 µmol/l, p < 0.01). DCT and DCG inhibited acetylcholine-induced increases in IP formation and MAP kinase phosphorylation (p44 and p42 ERK). DCG and DCT did not alter trypan blue exclusion or lactate dehydrogenase release from CHO-M3 cells. We observed the following rank order of potency (IC50 µmol/l) for inhibition of 3H-NMS by muscarinic antagonists and bile acids: NMS (0.0004) > 4-DAMP (0.009) > atropine (0.012) > DCT (170) > DCG (250). None of the bile acids tested were hydrolyzed by recombinant cholinesterase. At concentrations achieved in human bile, DC derivatives are natural muscarinic antagonists.
Vestibular Flap Urethroplasty for Strictures of the Female Urethra
Authors: Montorsi Francesco , Salonia Andrea , Centemero Antonella , Guazzoni Giorgio , Nava Luciano , Da Pozzo Luigi F. , Cestari Andrea , Colombo Renzo , Barbagli Guido , Rigatti Patrizio
Published: April 2003

Introduction: To assess the impact on subjective symptoms and flow patterns of a new surgical technique designed to correct strictures of the female distal urethra and urethral meatus. Materials and Methods: Seventeen patients (mean age 41.2 years) with symptomatic strictures of either the distal urethra or the urethral meatus entered the study. Patients reporting an AUA score >20, a diagnosis of bladder outlet obstruction according to the Abrams-Griffiths nomogram and the Schaefer linPURR diagram, urethral calibration <20 F and radiologic evidence of the stricture, were considered eligible for surgery. A pedicled flap isolated from the vaginal vestibule was anastomosed with two longitudinal running sutures along the two edges of an opened urethra. Results: In all cases, diffuse fibrosis of the urethral wall was demonstrated at histological examination. Mean (± SE) preoperative and 12-month follow-up results were as follows: AUA score 25.2 ± 2.1 vs. 8.4 ± 1.2 (p < 0.0001); peak flow rate (ml/s) 13.2 ± 1.2 vs. 36 ± 1.5 (p < 0.0001); detrusor pressure at Qmax (cm H2O) 45 ± 5 vs. 17 ± 3; residual urine volume (ml) 120 ± 5 vs. 20 ± 5 (p < 0.0001). Fifteen patients (88%) showed an unobstructed Abrams-Griffiths nomogram and a Schaefer linPURR diagram postoperatively. All but 2 cases (88%) could be calibrated at 28 F postoperatively and showed a normal urethral lumen at voiding cystourethrography. Complications were never noted. Conclusions: Female patients with symptomatic strictures of the distal urethra or urethral meatus may be treated efficaciously and safely with vestibular flap urethroplasty. Although this technique must be performed under optical magnification it is easy to perform and is not associated with complications.
Crypt Cell Production Rate in the Small Intestine of the Zinc-Supplemented Mouse
Authors: Duff Michael , Ettarh Rajunor R.
Published: April 2003

Zinc is a trace element which is necessary in the body and the daily requirement is usually provided mainly through food intake. The effects of zinc deficiency are multisystemic and in the gastrointestinal tract include ulceration and inflammation. Many of these effects in the mammalian small intestine are reversible by zinc replenishment in a manner that is thought to be linked to the effect of this element on intestinal mucosal cell kinetics. However, the effects of continued replenishment (supplementation) have not been closely examined. This study examined the effects of zinc supplementation on gut crypt cell production in zinc-replete animals. Fifteen CD-1 mice were given zinc sulphate (0.3 mmol/l) in tap water while a second (control) group of 15 mice received only tap water. After 14 days, the small intestine was removed, measured and divided into four equal lengths and then sampled at the midpoint of each of the resulting four segments. Whole crypt numbers and crypt cell production rate were determined for each intestinal site for both groups of mice. While crypt dimensions and crypt numbers in zinc-fed mice showed no significant change from control levels, the crypt cell production in zinc-fed mice was significantly increased and duration of mitosis reduced in the third (distal) intestinal segment when compared to values from control mice. These findings show that the addition of subtoxic quantities of zinc to diet in zinc-replete animals enhances cell production and indicate that the reversal of zinc deficiency-induced gut damage following dietary zinc replenishment may be due to a direct effect on cell kinetics.
Regional Differences in Yolk Platelet Degradation Activity and in Types of Yolk Platelets Degraded during Early Amphibian Embryogenesis
Authors: Komazaki Shinji , Tanaka Noriko , Nakamura Hiroaki
Published: April 2003

We compared the various regions of amphibian embryos before and during gastrulation to look for differences in activity and character in the degradation of yolk platelets (YPs). Cationic ferritin was used to examine YP degradation activity, the number of cationic-ferritin-containing endosomes and degrading YPs being compared among the various embryonic regions. In addition, we looked for differences in the types of degrading YPs among the various embryonic regions during early development. YP degradation activity was greatest in the animal and dorsal regions, and while large YPs (major axis more than 7 µm) were degraded preferentially in the animal region, small YPs (major axis less than 2 µm) were degraded preferentially in the dorsal region. These results suggest the possibility of different levels of YP degradation activity in different regions of the embryo, and also of regional differences in the types of YPs degraded during amphibian embryogenesis.
Medulloblastoma Metastatic to the Suprasellar Region at Diagnosis: A Report of Six Cases with Clinicopathologic Correlation
Authors: Helton Kathleen J. , Gajjar Amar , Hill D. Ashley , Boop Fredrick A. , Kun Larry E. , Langston James W.
Published: April 2003

The presence of metastatic disease in patients newly diagnosed with medulloblastoma remains one of the most important prognostic factors that determines event-free survival. In the present study, anatomic distribution and the signal characteristics and enhancement patterns of subtle anterior third ventricular recess metastases were compared with those of the original tumor; medical records were reviewed for clinical presentation, surgical stage, treatment and long-term outcomes. All foci were clinically occult; 5 out of 6 had negative cerebrospinal fluid cytology, and in 4 out of 6, the only evidence of metastatic disease was documented suprasellar disease that resolved or significantly improved following irradiation and chemotherapy. Histologically, 3 of the 6 patients had tumors with large cell/anaplastic features, a significant increase compared to the expected incidence of 4–8.8%. Patients with tumors that show large cell/anaplastic features may be at higher risk for early metastatic involvement of this unusual site.
Spontaneous Resolution of a Prepontine Arachnoid Cyst
Authors: Dodd Robert L. , Barnes Patrick D. , Huhn Stephen L.
Published: April 2003

Prepontine arachnoid cysts are rare developmental anomalies that occur almost exclusively in children. The symptomatic child typically suffers from hydrocephalus, visual impairment, endocrine dysfunction and/or cranial neuropathies. Some cysts, however, are discovered incidentally upon prenatal or postnatal imaging for other indications. While there is little doubt that surgical treatment should be initiated to help the symptomatic child, appropriate therapy for the asymptomatic patient is unclear. Although arachnoid cysts are often managed conservatively using serial imaging, the consequences of injury to surrounding structures with prepontine cysts often lowers the threshold for intervention. The natural history of asymptomatic prepontine arachnoid cysts is unknown. It has been reported that some cysts enlarge and cause symptoms, whereas others are stable for years. This report describes an index case of spontaneous resolution of a prepontine arachnoid cyst in a female infant over a 5-year period.
An Unusual Tuberous Sclerosis Case Presenting with Fibrillary Astrocytoma
Authors: Eren Suat , Polat Pinar , Erman Zekai
Published: April 2003

Tuberous sclerosis (TS) is an autosomal dominant disorder. It is characterized by hamartomatous lesions in various organs such as the brain, skin, kidneys and heart. Subependymal and parenchymal nodules occur in the cerebrum. Although giant cell astrocytoma may develop from these subependymal nodules, tumor formation is very rare in the cortical nodules. We present the clinical, computed tomography and magnetic resonance imaging findings of a fibrillary astrocytoma originating from a cortical tuber in a 4-year-old female with TS.
The Analgesic Domain of Interferon-α2b Contains an Essential Proline39 Residue
Authors: Wang Yun-Xia , Song Li-Hua , Chen Yi-Zhang , Jiang Chun-Lei
Published: April 2003

Objective: It has been demonstrated that there are structural and functional similarities between interferon-α (INF-α) and endorphins. We have reported that there are distinct domains in the IFN-α molecule that mediate immune and analgesic effects, respectively, and that the opioid-like analgesic effect of IFN-α is mediated by the µ opioid receptor, thus inferring that the analgesic domain of IFN-α consists of Tyr122 and the residues around Tyr122 in the tertiary structure. The aim of this work was to further explore the molecular basis for the analgesic domain of IFN-α. Methods: By using site-directed mutagenesis, the structure of IFN-α was changed and a mutant of IFN-α was obtained. Then, the antiviral activity and opioid-like analgesic activity of IFN-α were measured. Results: When the Pro39 residue of IFN-α, which is located close to the Tyr122 residue in the tertiary structure, was mutated to Gly, the analgesic activity of this mutant was lost completely, but the antiviral activity of IFN-α was maintained compared with wild-type IFN-α. Conclusions: Combining the sequence of the endomorphin, it is suggested that the Pro39 residue is one of the constituents of the analgesic domain of IFN-α and contributes to IFN-α binding to the µ opioid receptor.
Functional Imaging of the Auditory System: The Use of Positron Emission Tomography
Authors: Johnsrude Ingrid S. , Giraud Anne Lise , Frackowiak Richard S.J.
Published: April 2003

Modern brain imaging methods now afford unprecedented opportunities for the in vivo study of central auditory system function. Positron emission tomography (PET) has been used as a functional imaging technique for more than 15 years to study the distribution of cerebral haemodynamic changes associated with auditory stimulation, in subjects with normal and abnormal auditory function. Many of these studies concern processes related to, but not identical with, audition, such as speech perception, melodic processing and directed attention. Additionally, PET has been used to explore auditory perception in clinical populations such as cochlear implantees, neurosurgical candidates and people with tinnitus and auditory hallucinations. The spatial resolution of PET does not appear sufficient to address questions of a fine anatomical grain, e.g. exploring functional specialization within the primary and secondary auditory cortex. Nevertheless, PET has considerable potential as a tool in basic research on, and clinical assessment of, many auditory phenomena. Although functional magnetic resonance imaging can now be used for many studies for which formerly only PET was suitable, PET still possesses unique advantages. For example, it permits acquisition of data from inferior frontal and anterior temporal areas, can be used with subjects with cochlear and other implants (such as pacemakers) and can be used to map neurochemical pathways and receptors.
Serum Cystatin C Is a More Sensitive Marker of Glomerular Function than Serum Creatinine
Authors: Shimizu-Tokiwa Ayumi , Kobata Mami , Io Hiroaki , Kobayashi Noriyoshi , Shou Ichiyu , Funabiki Kazuhiko , Fukui Mitsumine , Horikoshi Satoshi , Shirato Isao , Saito Kensuke , Tomino Yasuhiko
Published: April 2003

We determined the relationship between the levels of serum cystatin C or creatinine (s-Cr) and the grade of creatinine clearance (CCr) in patients with various glomerular diseases. Serum samples from 96 patients with glomerular diseases were obtained from our hospital. The levels of serum cystatin C were measured using the Dade Behring Cystatin C assay with the automated Dade Behring Nephelometer II (BNII). CCr levels were classified into six groups according to the Guidelines of the Japanese Society of Nephrology as follows: grade 1 (normal renal function); grade 2 (slight decrease of renal function); grade 3 (moderate decrease of renal function); grade 4 (severe decrease of renal function); grade 5 (renal failure), and grade 6 (uremia). The mean levels of serum cystatin C in grade 3 patients were significantly higher than those in grade 1. The mean levels of serum cystatin C in grades 4, 5 and 6 patients were also significantly higher than those in grade 1. However, the mean levels of serum Cr in grade 3 patients were not significantly higher than those in grade 1. The levels of s-Cr in grades 4, 5 or 6 patients were significantly higher than those in grade 1. In this study, an increase of serum cystatin C levels occurred earlier than that of s-Cr in various glomerular diseases. It appears that the levels of serum cystatin C may provide early prognostic marker of patients with various glomerular diseases rather than the levels of s-Cr.
Angiotensin II Type 1 Receptor Gene Polymorphism in End-Stage Renal Disease
Authors: Buraczynska Monika , Ksiazek Piotr , Zaluska Wojciech , Spasiewicz Danuta , Nowicka Teresa , Ksiazek Andrzej
Published: April 2003

The genes of the renin-angiotensin system (RAS) are involved in progression of renal failure. We examined the A1166C polymorphism at the angiotensin II type 1 (AT1R) locus in patients with end-stage renal disease (ESRD). The distribution of genotype and allele frequencies was compared in 430 dialysis patients and 260 healthy controls. DNA samples were amplified by the polymerase chain reaction (PCR) and amplification products were digested with BsuRI restriction enzyme. In the presence of cytosine (C) there is a restriction site for this enzyme, giving a fragment of 231 bp (C allele), whereas undigested 255 bp fragment indicates the presence of the A allele. The higher frequency of combined AC and CC genotypes was observed in the patient group than in controls (48.6 vs. 39.5%, p < 0.05). The average time from the onset of renal disease to ESRD in patients with C allele was significantly shorter than in those with AA genotype (6.3 vs. 13 years, p < 0.01). Positive family history of renal disease in patients with AC/CC genotype seems to increase this effect. Our results indicate that the presence of C allele of the AT1R locus polymorphism might be associated with faster deterioration of renal function.
Acute Interstitial Nephritis Associated with the Use of Mesalazine in Inflammatory Bowel Disease
Authors: Frandsen Niels Erik , Saugmann Søren , Marcussen Niels
Published: April 2003

Background: In the last 10 years several reports have linked oral 5-aminosalicylic acid (5-ASA) therapy to acute and chronic tubulointerstitial nephritis, but to our knowledge only 2 patients have been reported with terminal end-stage renal disease due to mesalazine (5-ASA). After 1 year of treatment with 5-ASA annual monitoring of serum creatinine is recommended. Results: We report the development of end-stage renal disease in a patient 10 months after the last assessment of serum creatinine, which was normal at 71 µmol/l. Conclusion: Because of this dangerous side effect, we would like to recommend 6-monthly assessment of renal function.
Mechanisms and Kinetics of Bowman’s Epithelial-Myofibroblast Transdifferentiation in the Formation of Glomerular Crescents
Authors: Fujigaki Yoshihide , Sun Di Fei , Fujimoto Taiki , Suzuki Takayuki , Goto Tetsuo , Yonemura Katsuhiko , Morioka Tetsuo , Yaoita Eishin , Hishida Akira
Published: April 2003

Background: We investigated the mechanisms and kinetics of Bowman’s epithelial-myofibroblast transdifferentiation in the formation of glomerular crescents. Methods: Crescentic glomerulonephritis was induced by i.v. injection of rabbit anti-rat glomerular basement membrane antiserum in WKY rats. Results: Cellular crescents (83.5% of glomeruli) were first observed at day 7 after disease induction. Immunostaining of alpha-smooth muscle actin (alpha-SMA), as a marker for the myofibroblast phenotype, was found in some periglomerular regions as early as day 3, when it was also seen in parietal epithelial cells (PEC) of Bowman’s capsule at day 5 and in crescent formation at day 7. Proliferation marker Ki67-positive PEC was found at day 3, and double Ki67- and alpha-SMA-positive PEC could be seen at day 5. The migratory figure of PEC with the expression of alpha-SMA was found by immunoelectron microscopy. At day 7, some crescent cells were stained positive for PEC marker, protein gene product 9.5, in association with alpha-SMA or Ki67. Expression of transforming growth factor (TGF)-β receptor types I and II, as well as platelet-derived growth factor (PDGF) receptor β and PDGF-B increased in PEC as early as day 3. At day 5 marked deposition of cellular and common fibronectin, but not other extracellular matrix components examined was found in Bowman’s spaces where ED 1-positive macrophages infiltrated. Conclusions: PEC may be stimulated to proliferate and/or transdifferentiate into myofibroblast phenotype possibly by action of TGF-β and PDGF and/or binding of fibronectin to PEC, then migrate and/or proliferate, participating in glomerular crescents.
Hospitalizations for Valvular Heart Disease in Chronic Dialysis Patients in the United States
Authors: Abbott Kevin C. , Agodoa Lawrence Y.
Published: April 2003

Background: Valvular heart disease has not been studied in a national population of end stage renal disease patients. Methods: 327,993 dialysis patients in the United States Renal Data System initiated from 1 January 1992 to 30 June 1997 were analyzed in a historical cohort study of patients hospitalized for valvular heart disease (ICD9 Code 424.x, excluding endocarditis, and 394.x-397.x). Results: 2,778 dialysis patients were hospitalized for VHD (incidence rate, 3.57 per 1,000 person years), and dialysis patients had an age-adjusted incidence ratio for valvular heart disease of 5.06 (95% confidence interval, 4.00–6.42) compared to the general population in 1996. In Cox regression analysis, time to hospitalization for valvular heart disease was associated with earlier year of first dialysis, increased age, congestive heart failure and use of erythropoietin prior to dialysis, while African-American race (AHR 0.62, 0.52–0.74) was associated with decreased risk of hospitalization for valvular heart disease. Patients hospitalized for valvular heart disease had increased mortality compared to all other dialysis patients (adjusted hazard ratio by Cox regression 1.35, 95% CI, 1.25–1.46). Conclusions: Dialysis patients were at increased risk for hospitalizations for valvular heart disease compared to the general population, which substantially decreased patient survival. The reasons for the decreased risk of African-Americans on chronic dialysis for this complication should be the subject of future trials.
Chronic Hypercortisolemia Inhibits Dopamine Synthesis and Turnover in the Nucleus accumbens: An in vivo Microdialysis Study
Authors: Pacak Karel , Tjurmina Olga , Palkovits Miklós , Goldstein David S. , Koch Christian A. , Hoff Thomas , Chrousos George P.
Published: April 2003

Over 60% of patients with Cushing’s syndrome suffer from major depression, which frequently abates after correction of the hypercortisolism. The mesolimbic and mesocortical dopaminergic (DAergic) systems are thought to participate in psychiatric disorders. In this study, we investigated whether hypercortisolemia affects indices of DAergic activity in the nucleus accumbens (NAc) and the prefrontal cortex (PFC) of freely moving rats. Cortisol (CORT, 25 mg/kg/day) was infused subcutaneously for 7 days via an osmotic minipump. Microdialysate collection (30-min periods, 2 µl/min) began 24 h after probe placement. Concentrations of dihydroxyphenylalanine (DOPA) in interstitial fluid in the nucleus accumbens (NAc) and perifrontal cortex (PFC) were measured before and after local perfusion with NSD-1015, an irreversible inhibitor of L-aromatic amino acid decarboxylase, to assess local dopamine (DA) biosynthesis. The sum of microdialysate DA, dihydroxyphenylacetic acid, and homovanillic acid was used as an index of local DA turnover. DOPA accumulation after NSD-1015 was markedly attenuated in CORT-treated compared with saline-treated animals (5,703 ± 1,849 vs. 10,902 ± 2,454 pg/ml; p < 0.01). In contrast, the two groups did not differ in DOPA accumulation in the PFC. Values for the turnover index of DA were also significantly lower in CORT-treated animals in the NAc but not in the PFC. The results indicate that CORT inhibits DA synthesis and turnover in the NAc but not in the PFC. Region-specific CORT-induced inhibition of DAergic activity may help to explain depressive symptoms in patients with chronic hypercortisolemia and normalization after medical or surgical correction of hypercortisolism.
Photochemoprevention by Botanical Antioxidants
Authors: Afaq Farrukh , Mukhtar Hasan
Published: April 2003

The trend towards an increase in incidence and higher prevalence of skin cancer makes identification of effective chemopreventive agents an urgent priority. Excessive exposure to solar ultraviolet (UV) B radiation has been implicated as its main cause. Since these trends are likely to continue in the foreseeable future, the adverse effect of UVB has become a major human health concern. Therefore, the development of novel strategies to reduce the occurrence of skin cancer has become a highly desirable goal. Because UV radiation is known to cause excessive generations of reactive oxygen species (ROS) which in turn results in a situation known as oxidative stress, the approaches aimed at counteracting ROS production may be useful for the prevention of skin cancer. One approach to reduce its occurrence is through ‘photochemoprotection’, which we define as ‘the use of agents capable of ameliorating the adverse effects of UVB on the skin’. Among many photochemoprotective agents, botanical antioxidants are showing promise. This review focuses on photochemopreventive effects of selected botanical antioxidants. We suggest that the use of botanical antioxidants in combination with the use of sunscreens and educational efforts to avoid excessive sun exposure may be an effective strategy for reducing incidence of skin cancer and other UV-mediated damages in humans.
Photocarcinogenesis: UVA vs. UVB Radiation
Authors: de Gruijl Frank R.
Published: April 2003

Recent research is revealing combinations of disturbed oncogenic and tumor-suppressive signaling pathways by altered or missing genes in skin cancers: mutated PTCH (in the mitogenic Sonic Hedgehog pathway) and mutated p53 tumor suppressor gene in basal cell carcinomas (BCC), possibly an activated mitogenic RAS pathway and mutated p53 in squamous cell carcinomas (SCC), and possibly an activated MET/RAS pathway and inactive p16INK4a tumor suppressor in cutaneous melanomas. UV radiation damages DNA and can give rise to genomic alterations, varying from point mutations to crude chromosomal dislocations. UVB radiation (wavelength band 280–315 nm) is more carcinogenic than UVA radiation (315–400 nm) in experimental induction of SCC. The impact of UVB radiation can be clearly inferred from the characteristic point mutations in p53 found in human SCC and BCC. In contrast to UVB radiation, much of the mutagenic and carcinogenic action of UVA radiation appears to be mediated through reactive oxygen species (ROS). Experiments have shown that UVA1 (340–400 nm) exposure induces SCC largely without the characteristic point mutations in p53. Both UVB and UVA radiation can give rise to ROS-related point mutations (e.g. G to T) and crude genomic alterations (e.g. deletions) which may not be recognized as caused by UV radiation.
The Cardiovascular Risk Factor Homocysteine Is Not Elevated in Young Women with Hyperandrogenism or Hypoestrogenism
Authors: Morgante Giuseppe , la Marca Antonio , Setacci Francesco , Setacci Carlo , Petraglia Felice , De Leo Vincenzo
Published: April 2003

The aim of the present study was to determine whether the plasma concentrations of homocysteine (Hcy) are elevated in women with hypogonadotropic hypogonadism (a condition of chronic hypoestrogenism) and in women with polycystic ovarian syndrome (PCOS, a syndrome characterized by hyperandrogenemia). A cross-sectional study was performed. The plasma concentrations of Hcy were determined in 12 normal-cycling women, in 14 women with hypogonadotropic amenorrhea (HA), and in 20 women with PCOS. The plasma LH, FSH, E2, testosterone, free testosterone, and androstenedione levels were measured. The blood samples analyzed were taken during the early follicular phase in controls and without regard to the menstrual phase in the patients. Twelve normal-cycling women were compared with 14 women with HA and with 20 women with PCOS. Women with HA or PCOS have plasma concentrations of Hcy similar to those of healthy women with normal menstrual cycles. The results suggest that young women with chronic hypoestrogenism (HA) or hyperandrogenism (PCOS) have plasma concentrations of Hcy similar to those of healthy women with normal menstrual cycles.
A Prospective Comparative Study on IVF Outcomes with Either Purified FSH or Human Menopausal Gonadotrophin in Downregulated Normogonadotrophic Women
Authors: Ismail Aboul Foutouh , Hesham Al-Inany , Salah Zaki , Khaled M. , Fouad Nahas , Ashraf Nasr , Hatem Shawky , Hamdi Badrawi
Published: April 2003

Objective: In compare the use of purified follicle-stimulating hormone with that of a preparation containing follicle-stimulating hormone and luteinizing hormone in infertile females undergoing IVF. Design: Open-labelled prospective controlled single-center study. Setting: Nile Badrawy IVF unit. Participants: 153 infertile females undergoing their first cycle of IVF divided into 2 groups. Interventions: Ovarian stimulation was done with either highly purified FSH for group 1 (n = 75) or human menopausal gonadotrophin group 2 (n = 78) after pituitary desensitization commenced in the midluteal phase of the preceding cycle. Monitoring was performed by ultrasound transvaginal oocyte retrieval followed by IVF and transfer of three embryos. Outcomes: Number of oocytes >18 mm at day of hCG, fertilization rate, embryo transfer rate, clinical pregnancy rate and incidence of ovarian hyperstimulation syndrome. Results: The response to ovarian hyperstimulation was similar in both groups. The number of follicles >18 mm achieved at day of hCG was 12.3 ± 0.9 (mean ± SEM) following stimulation with 38.3 ± 0.9 ampoules of Fostimon The Menogon-treated group needed 39.1 ± 0.8 ampoules to produce 11.6 ± 0.7 follicles. Fertilization rate (2PN/cell) was 58.6 vs. 64.2% in the Fostimon and Menogon group, respectively (p > 0.05). The number of embryos transferred per woman was 3.1 ± 0.1 in the Fostimon group and 3.6 ± 0.1 in the Menogon group. The pregnancy rate per woman was 33.3 vs. 25.6% in the Fostimon- and Menogon-treated groups, respectively (p > 0.05). Miscarriage rate was 16 vs 20%, respectively. However, the incidence of multiple pregnancies was significantly higher in the Fostimon-treated group (32%) vs. 10% only in the Menogon-treated group (p < 0.01). Conclusion: Purified FSH yields similar clinical outcome to hMG in terms of oocytes retrieved and clinical pregnancies in a standard IVF regimen.
Outcome of Selective Peripheral Denervation for Cervical Dystonia
Authors: Meyer C.H.A.
Published: April 2003

30 patients with cervical dystonia were treated by selective peripheral denervation (SPD) (Bertrand procedures). Follow-up 12–75 (median 26) months after surgery showed strong group improvements in the clinical state (Toronto Western Spasmodic Torticollis Rating Scale) and in performance of ADL, impairment, lifestyle and degree of incapacity (rating scales used by Australia’s Department of Veterans’ Affairs). SPD can give long-term benefits important clinically, in the home and in society.
Targeting the Subthalamic Nucleus
Authors: Aziz T.Z. , Nandi D. , Parkin S. , Liu X. , Giladi N. , Bain P. , Gregory R.G. , Joint C. , Scott R.B. , Stein J.F.
Published: April 2003

The small size and surrounding neuronal structures and fibre tracts make the STN a difficult stereotactic target. In this article we present the technique used by us to target the STN. Our combined experience from two centres comprises 18 lesions and 27 stimulator implants in the STN. Our criteria for patient selection and the use of MRI, frame-on CT and volumetric image fusion are presented. The role of a movement disorder specialist neurologist in the operating theatre, local field potential recording, impedance monitoring, macrostimulation, post-operative CT/MRI and test stimulation are detailed.
Investigation of Extra-Temporal Epilepsy
Authors: Roberts D.W. , Jobst B.C. , Siegel A.M. , Lewis P.J. , Darcey T.M. , Thadani V.M. , Williamson P.D.
Published: April 2003

Medically intractable epilepsy of extra-temporal origin can represent a difficult therapeutic challenge. Our Epilepsy Service has managed these patients using standard investigative methods as well as ictal SPECT and intracranial electrode recording. In the present series of patients, image-guided surgery was used for all electrode implantation and resective surgery. Seizure localization and successful resection were achieved in 70–80% of 42 patients with follow-up of at least one year. Normal MRI and previous failed intracranial investigation were not associated with poorer outcome.
Electrical Stimulation for Epilepsy: Stimulation of Hippocampal Foci
Authors: Velasco Francisco , Velasco Marcos , Velasco Ana Luisa , Menez Diana , Rocha Luisa
Published: April 2003

Subacute and chronic continuous electrical stimulation at the epileptic focus in the hippocampus or parahippocampal cortex at 130 Hz, 0.21– 1.0 ms, 2.5–3.5 V (about 200–300 µA) induces a decrease in focal EEG epileptic interictal activity and also in the occurrence of clinical seizures. This may represent an alternative for the treatment of temporal lobe seizures originated in bilateral independent temporal lobe foci or occurring in patients where one is uncertain whether memory deficit might result from ablative procedures.
The Role of the Pedunculopontine Tegmental Nucleus in Experimental Parkinsonism in Primates
Authors: Matsumura Masaru , Kojima Jun
Published: April 2003

To clarify the role of the pedunculopontine tegmental nucleus (PPN) in motor behavior, we have conducted a series of experiments in primates. In the first part, PPN was damaged locally with kainic acid, which resulted in mild hemiparkinsonism in the contralateral limbs. In the second part, muscimol (a GABA agonist) was locally injected into the PPN area in monkeys who had been trained to perform a lever-pull movement with an arm, resulting in a slowness of movement and a delay of the movement onset. In the third part, a dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was systemically injected in monkeys with prior PPN lesioning. These monkeys developed no, or if any, very mild parkinsonism. PPN lesioning was supposed to have protected the nigral neurons from the MPTP- toxicity. The PPN facilitates the motor system through its nigral projection. The decreased activity of the PPN may underlie the pathophysiology of parkinsonism.
Overexpression of Fatty Acid Synthase in Oesophageal Squamous Cell Dysplasia and Carcinoma
Authors: Nemoto Tsuyoshi , Terashima Shinya , Kogure Michihiko , Hoshino Yutaka , Kusakabe Takashi , Suzuki Toshimitsu , Gotoh Mitsukazu
Published: April 2003

Objective: The expression of fatty acid synthase (FAS), an enzyme necessary for de novo fatty acid synthesis, has been examined in several types of tumours so far, but not in oesophageal cancer and dysplasia. Methods: We examined the immunohistochemical reactivity of FAS in 4 normal adult oesophagi, 14 dysplastic oesophageal lesions, and 80 squamous cell carcinomas and 6 cases with 4 special types of malignancies of the oesophagus. We also analysed the correlation between FAS expression and various clinicopathological features and long-term survival in patients with oesophageal cancer. Results: In the normal oesophagus, only faint cytoplasmic FAS expression was observed in cells of the basal layer. In contrast, FAS-positive cells were found in 92.9% of cases of dysplasia and 96.5% of cases of carcinoma including 6 cases with a specific histological subtype. However, high expression of FAS did not correlate with either clinicopathological features or prognosis of patients with oesophageal cancer. Conclusion: Our results demonstrate that FAS is expressed in almost all oesophageal carcinomas of both usual and special types and dysplastic lesions, suggesting that FAS may be upregulated continuously from the early stage of oesophageal squamous cell carcinogenesis to established carcinoma.
Increased Expression but Not Genetic Alteration of BRG1, a Component of the SWI/SNF Complex, Is Associated with the Advanced Stage of Human Gastric Carcinomas
Authors: Sentani Kazuhiro , Oue Naohide , Kondo Humihiro , Kuraoka Kazuya , Motoshita Junichi , Ito Reiko , Yokozaki Hiroshi , Yasui Wataru
Published: April 2003

BRG1, a component of the SWI/SNF complex, regulates gene transcription through chromatin remodeling. Certain human cancer cell lines have been shown to contain homozygous deletions or mutations, half of which are concentrated in exons 4 and 10, resulting in aberrant BRG1 expression. We examined the expression of BRG1 in 38 gastric carcinomas and corresponding nonneoplastic mucosa by using the quantitative real-time RT-PCR method. Twenty-three carcinomas (61%) showed increased BRG1 expression in tumor tissue in comparison with that in nonneoplastic mucosa. The T/N ratio (the expression level of BRG1 mRNA in tumor tissues relative to those in corresponding nonneoplastic mucosa) in advanced cases of gastric carcinoma (stages III and IV) was significantly higher than that in cases of stage I and II carcinoma (p = 0.029). Furthermore, gastric carcinomas with lymph node metastasis showed a tendency to express BRG1 at a higher level than gastric carcinomas without metastasis (p = 0.097). We also searched for genetic alterations of the BRG1 gene in 8 gastric carcinoma cell lines and 33 primary gastric carcinomas by PCR-SSCP analysis. No SSCP variants in exons 4, 10 and 16 of the BRG1 gene were found in both gastric carcinoma cell lines and primary gastric carcinomas. These results suggest that, although genetic abnormality of BRG1 might be rare, an increased expression of BRG1 might be associated with the development and progression of gastric carcinoma.
Effects of Different HIV Strains on Thymic Epithelial Cultures
Authors: Kourtis Athena P. , Ibegbu Christian C. , Scinicarrielo Franco , Lee Francis K.
Published: April 2003

The thymus is the major site for T cell development; interactions of developing thymocytes with thymic epithelial cells are critical for normal thymopoiesis. We set out to determine whether thymic epithelial cells can be infected by HIV strains that cause different patterns of disease progression in infected infants. Thymic epithelial cell monolayers were prepared from normal thymus of infants, removed at the time of cardiac surgery. We infected the thymic epithelial cell monolayers with different strains of HIV, including laboratory strains and clinical strains from 3 of our pediatric HIV-infected patients with different patterns of disease progression. We found that different strains of HIV have different ability to infect thymic epithelial cells; the ability to infect thymic epithelial cells may not be directly related to CCR5/CXCR4 usage. Different HIV strains thus appear to employ different mechanisms by which they affect thymic components.
Iodized Oil as a Complement to Iodized Salt in Schoolchildren in Endemic Goiter in Romania
Authors: Simescu M. , Varciu M. , Nicolaescu E. , Gnat D. , Podoba J. , Mihaescu M. , Delange F.
Published: April 2003

Objective: To evaluate the long-term efficacy and possible side effects of low doses of iodized oil on iodine nutrition and thyroid function in endemic goiter in Romania. Methods: Random selection of 214 schoolchildren aged 6–14 years. Serial measurements of urinary iodine, thyroid volume with ultrasound, serum concentrations of thyrotropin, free thyroxine, thyroglobulin and thyroid autoantibodies before and up to 2 years after the oral administration of 200 mg iodine in iodized oil. Results: Urinary iodine concentrations indicated a moderate iodine deficiency before therapy, sharply increased soon after therapy and slowly decreased thereafter but remained within the normal range up to more than 1 year after therapy. The prevalence of goiter was 29% before the administration of iodized oil and 9% 1 year later. Thyroid function tests and autoantibodies were normal before and up to 2 years after therapy. Conclusion: A single dose of 200 mg iodine from oral Lipiodol® appears adequate and safe for correcting moderate iodine deficiency in children.