bluuebunny/crossref_metadata_2025 huggingface dataset:
ROSIGLITAZONE, A PEROXISOME PROLIFERATOR‐ACTIVATED RECEPTOR‐γ LIGAND, REDUCES INFARCTION VOLUME AND NEUROLOGICAL DEFICITS IN AN EMBOLIC MODEL OF STROKE
Authors: Allahtavakoli Mohammad , Shabanzadeh Alireza P , Sadr Seyed Shahabeddin , Parviz Mohsen , Djahanguiri Bijan
Published: October 2006

Stroke is accompanied by a robust inflammatory response, glutamate‐mediated excitotoxicity, release of reactive oxygen species and apoptosis. Thiazolidinediones, which target the nuclear receptor peroxisome proliferator‐activated receptor (PPAR)‐g, have been reported recently to exhibit potent anti‐inflammatory and anti‐oxidant actions and inhibit both neural excitotoxicity and apoptosis.

The present study was conducted to determine whether rosiglitazone, a potent thiazolidinedione for PPAR‐g, would show efficacy against the cerebral infarction and neurological dysfunctions induced by embolic middle cerebral artery (MCA) occlusion in the rat.

Focal ischaemic injury was induced by embolizing a preformed clot into the MCA. Rosiglitazone was dissolved in dimethyl sulphoxide and injected i.p. 1 h before MCA occlusion at doses of 0.33, 0.1, 0.3 or 1 mg/kg. In addition, 1 mg/kg rosiglitazone was used immediately or 4 h after embolization. Forty‐eight hours after MCA occlusion, brains were removed, sectioned and stained with a 2% solution of 2,3,5‐triphenyltetrazolum chloride and analysed using a commercial image‐processing software program.

When rosiglitazone was administered 1 h before embolization, it significantly reduced infarct volume by 48.2, 68.4% and 70.3% at doses of 0.1, 0.3 and 1 mg/kg, respectively (P < 0.001). Administration of rosiglitazone (1 mg/kg) immediately or 4 h after stroke also reduced infarct volume by 67 and 50.8%, respectively (P < 0.001). Rosiglitazone‐treated rats also demonstrated improved neurological functions. However, there were no statistically significant differences between control and treated groups in terms of brain oedema at 48 h after ischaemic injury.

The findings of the present study may support the idea of a potential benefit of thiazolidinediones in the management of ischaemic stroke.
Cpu0507, An Endothelin Receptor Antagonist, Improves Rat Hypoxic Pulmonary Artery Hypertension And Constriction In Vivo And In Vitro
Authors: Yuan Sheng‐hua , Dai De‐zai , Guan Li , Dai Yin , Ji Min
Published: October 2006

The Aim Of The Present Study Was To Test The Efficacy Of The Novel Endothelin (Et) Receptor Antagonist Cpu0507 In Treating Rat Hypoxic Pulmonary Hypertension (Ph) In Vivo And In Vitro And To Explore The Role Of The Et‐1 System In The Disease.

Male Sprague‐dawley Rats (220 ± 20 G) Were Divided Into Four Groups: (I) Control; (Ii) Untreated Hypoxic (28 Days Hypoxia); (Iii) Hypoxic Rats Treated In The Last 5 Days Of Hypoxia With Nifedipine(5 Mg/kg Per Day, P.o.); And (Iv) Hypoxic Rats Treated In The Last 5 Days Of Hypoxia With Cpu0507 (20 Mg/kg Per Day, S.c.). Effects Of Treatments On Haemodynamics And Biochemical Data, As Well As Functional Assessments Of The Isolated Pulmonary Artery, Were Determined In Vivo And In Vitro.

It Was Found That Cpu0507 Reduced The Elevated Pulmonary Arterial Pressure And Right Heart Weight Index And Restored Abnormalities In Nitric Oxide (No), Malondialdehyde And No Synthase (Nos) In The Serum And Superoxide Dismutase, Hydroxyproline And Nos In Pulmonary Homogenates. In Addition, Cpu0507 Restored Altered Pulmonary Vasoconstrictor And Vasodilator Responses. Vascular Constriction And Dilatation Of Untreated Pulmonary Arteries Were Reverted Effectively Towards Normal Following Exposure Of Artery Rings To Cpu0507 In Vitro.

In Conclusion, The Results Indicate That Hypoxic Ph Is Relieved Significantly By Cpu0507 In Vivo And In Vitro And The Effects Are Presumed To Be Mediated By Suppression Of The Et–reactive Oxygen Species Axis.
l‐GLUTAMATE AND GLUTAMINE IMPROVE HAEMODYNAMIC FUNCTION AND RESTORE MYOCARDIAL GLYCOGEN CONTENT DURING POSTISCHAEMIC REPERFUSION: A RADIOACTIVE TRACER STUDY IN THE RAT ISOLATED HEART
Authors: Støttrup Nicolaj B , Kristiansen Steen B , Løfgren Bo , Hansen Bo Falck , Kimose Hans‐Henrik , Bøtker Hans Erik , Nielsen Torsten Toftegaard
Published: October 2006

l‐Glutamate and glutamine have been suggested to have cardioprotective effects. However, the issue is controversial and the metabolic mechanisms underlying a beneficial effect are not well understood.

In the present study we investigated the effects of l‐glutamate and glutamine on haemodynamic recovery, the rate of de novo glycogen synthesis and myocardial glucose uptake during postischaemic reperfusion.

. Hearts from male Wistar rats (250–300 g) were divided into three groups as follows: (i) control (n = 12); (ii) l‐glutamate (n = 12); and (iii) glutamine (n = 12). Hearts were mounted in a Langendorff preparation and perfused with oxygenated Krebs’–Henseleit solution at 80 mmHg and 37C. Global ischaemia for 20 min was followed by 15 min reperfusion, during which l‐glutamate (50 mmol/L) or glutamine (20 mmol/L) were administered. Left ventricular developed pressure (LVDP), de novo synthesis of glycogen using [14C]‐glucose and myocardial glucose uptake using d‐[2‐3H]‐glucose were measured.

l‐Glutamate and glutamine increased postischaemic LVDP (P < 0.01 vs control hearts for both). l‐Glutamate and glutamine increased de novo glycogen synthesis by 78% (P < 0.001) and 55% (P < 0.01), respectively. At the end of reperfusion, total myocardial glycogen content was increased by both l‐glutamate and glutamine (5.7 ± 0.3 and 6.2 ± 0.7 mmol/g wet weight, respectively; P < 0.05 and 0.01, respectively) compared with that in control hearts (3.6 ± 0.4 mmol/g wet weight). Neither l‐glutamate nor glutamine affected myocardial glucose uptake during reperfusion.

. Improved postischaemic haemodynamic recovery after l‐glutamate and glutamine supplementation during reperfusion is associated with increased de novo glycogen synthesis, suggesting a favourable modulation of intracellular myocardial carbohydrate metabolism.
STRUCTURAL AND FUNCTIONAL CHARACTERIZATION OF INTERACTIONS BETWEEN THE DIHYDROPYRIDINE RECEPTOR II–III LOOP AND THE RYANODINE RECEPTOR
Authors: Casarotto Marco G , Cui Yanfang , Karunasekara Yamuna , Harvey Peta J , Norris Nicole , Board Philip G , Dulhunty Angela F
Published: October 2006

Excitation–contraction coupling in skeletal muscle is dependent on a physical interaction between the dihydropyridine receptor (DHPR) and the ryanodine receptor (RyR).

A number of peptides derived from the II–III loop region of the DHPR have been shown to be functionally active in stimulating the release of calcium via RyR channels. Their function has been found to correlate with the presence of a basic helical region located at the N‐terminus of the II–III loop.

The entire recombinant skeletal DHPR II–III loop is an efficient activator of RyR1 and RyR2.

The skeletal DHPR II–III loop is comprised of a series of a‐helices, but its tertiary structure has been determined to be unstructured and flexible.

Fluorescence quenching experiments have been used to identify and measure the binding affinity of the II–III loop with fragments of the RyR.
Gastric longitudinal shortening may occur during gastric phase III activities in man
Authors: Ino Kyoko , Kusano Motoyasu , Ohwada Tsuneo , Kawamura Osamu , Toki Munetoshi , Sekiguchi Toshikazu , Mori Masatomo
Published: October 2006

Background and Aim:  The aim of this study was to determine whether the gastric longitudinal shortening occurs during the gastric phase III in man.

Methods:  Intragastric pH and gastroduodenal motility were simultaneously measured by means of a 24‐h ambulatory recording system in 14 healthy volunteers. In nine subjects (group A), the catheter assembly was endoscopically clipped to the gastric mucosa with the middle transducer and the distal pH sensor in the antrum. In the remaining five subjects (group B), measurements were performed without securing the assembly.

Results:  In 23 of the 25 gastrointestinal interdigestive migrating complexes in group A, the distal and middle transducers showed characteristic duodenal contractions (11–12 c.p.m.). Neutralization was noted at the distal pH sensor. Similar phenomena were observed during all 15 gastrointestinal interdigestive migrating complexes in group B. The catheter assemblies escaped into the duodenum despite the fact that they were secured to the stomach. This may be explained by gastric longitudinal shortening during gastric phase III activities.

Conclusions:  Studies of intragastric physiology with test catheters must take the effect of gastric longitudinal shortening during phase III into consideration.
Recurrent hepatocellular carcinoma has an increased risk of subsequent recurrence after curative treatment
Authors: Yamashiki Noriyo , Yoshida Haruhiko , Tateishi Ryosuke , Shiina Shuichiro , Teratani Takuma , Yoshida Hideo , Kondo Yuji , Oki Takamasa , Kawabe Takao , Omata Masao
Published: October 2006

Background and Aim:  Local ablation therapy has been shown to be effective for small hepatocellular carcinoma (HCC); however, HCC recurrence is very frequent even after apparently curative treatment. In particular, recurrent HCC may be more prone to subsequent recurrence, although quantitative data are lacking. The aim of this study was to evaluate the difference in the risk for subsequent recurrence, if any, between primary and recurrent cases.

Methods:  A retrospective analysis was conducted of 376 patients with HCC (uninodular and ≤5 cm, or 2–3 nodules each ≤3 cm) who underwent local ablation therapy. There were 207 primary cases (group I), 100 with first recurrence (group II), and 69 with second or later recurrence (group III). After confirming complete ablation, each patient was followed up for recurrence. Risk factors for recurrence‐free survival were analyzed using proportional hazard regression.

Results:  The median time to recurrence, as estimated by Kaplan–Meier method, was 30 months in group I, 23 months in group II, and 11 months in group III (P < 0.001). Multivariate proportional hazard regression analysis reveled that group (i.e. previous recurrence) was the strongest predictor of subsequent recurrence; compared to group I, group II showed a hazard ratio of 1.456 (P = 0.015) and group III, 3.011 (P < 0.0001). α‐Fetoprotein level >100 ng/mL, treatment other than radiofrequency ablation, HCV antibody positivity, and tumor multinodularity also remained as significant predictors.

Conclusion:  Hepatocellular carcinoma at second or later recurrence is three times as prone to subsequent recurrence as is primary HCC, when compared with adjustment for other tumor and hepatic factors.
Rho/Rho kinase is a key enzyme system involved in the angiotensin II signaling pathway of liver fibrosis and steatosis
Authors: Kitamura Kumi , Tada Shinichiro , Nakamoto Nobuhiro , Toda Kyoko , Horikawa Hitomi , Kurita Satoshi , Tsunematsu Satoshi , Kumagai Naoki , Ishii Hiromasa , Saito Hidetsugu , Hibi Toshifumi
Published: October 2006

Background and Aim:  The molecular mechanisms underlying the involvement of the renin‐angiotensin system in hepatic fibrosis are unclear. Recently, it was reported that a Rho kinase inhibitor prevented fibrosis of various tissues and that the Rho/Rho kinase pathway was involved in the renin‐angiotensin system of vascular smooth muscle cells. In this study, the involvement of the Rho/Rho kinase pathway on angiotensin II signaling in liver fibrogenesis and generation of steatosis was investigated.

Methods:  Rats were fed a choline‐deficient/L‐amino acid‐defined (CDAA) diet continuously and treated with a Rho kinase inhibitor, Y‐27632, and an angiotensin II receptor blocker, TCV‐116. Liver histology and hepatic stellate cell activation were analyzed. Free radical production was detected by 4‐hydroxynonenal and 8‐hydroxy‐2′‐deoxyguanosine immunostaining and the expression of tumor necrosis factor‐α was examined. Isolated hepatic stellate cells were pretreated with a Rho kinase inhibitor, Y‐27632, or an angiotensin II receptor blocker, CV‐11974, and stimulated with angiotensin II, and mRNA expression of transforming growth factor‐β and α‐smooth muscle actin was analyzed.

Results:  Both the angiotensin II receptor blocker and the Rho kinase inhibitor improved fibrosis and steatosis of the liver in CDAA‐fed rats. The increase in the number of hepatocytes positive for 4‐hydroxynonenal and 8‐hydroxy‐2′‐deoxyguanosine in CDAA‐fed rats was significantly prevented by the angiotensin II receptor blocker and the Rho kinase inhibitor. The levels of tumor necrosis factor‐α mRNA in the liver of CDAA‐fed rats were significantly increased and this increase was significantly inhibited by treatment with the angiotensin II receptor blocker and the Rho kinase inhibitor. mRNA expression of transforming growth factor‐β and α‐smooth muscle actin stimulated by angiotensin II was also significantly suppressed by these two drugs.

Conclusion:  These results suggest that the Rho/Rho kinase pathway is at least partly involved in the renin‐angiotensin system and plays an important role in hepatic fibrosis and steatosis.
Vaccination for the paediatrician
Authors: Wood Nicholas , McIntyre Peter , Wong Melanie
Published: October 2006

Abstract:  In most of Australia, general practitioners manage routine childhood vaccination schedules. However, paediatricians have an important role and need to have a thorough understanding of vaccination, particularly as it interfaces with other medical care. This is challenging as the Australian Standard Vaccination Schedule has undergone some substantial changes over the past 4 years, with the addition of meningococcal C conjugate, 7 valent pneumococcal conjugate, varicella and inactivated polio vaccines. Paediatricians are frequently the first port of call for advice on vaccination schedules for children with special needs, in relation to either vaccine efficacy or the risk of side effects. Categories include children with a range of chronic diseases, immunosuppression, premature infants and immigrant children. Advice about specific vaccines such as varicella, inactivated polio, influenza or multivalent vaccines and revaccination after adverse events is also often sought. The aim of this article is to update paediatricians on vaccination recommendations and relevant reference sources. The first part of this article discusses groups with special vaccination requirements. The second part discusses the use of individual vaccines in these children.
Low incidence of alpha 1‐antitrypsin deficiency among Filipinos with neonatal cholestatis
Authors: Tan Josephine J , Cutiongco‐dela Paz Eva Maria , Avila Jose Maria C , Gregorio Germana V
Published: October 2006

Aim:  Alpha 1‐antitrypsin (AAT) deficiency is the most common genetic cause of liver disease in children. The Pi*S carrier rate among Filipinos is <1%. Its significance in Filipino infants with neonatal cholestasis has not been investigated. The aim of the study was to determine the incidence of AAT deficiency among Filipino infants presenting with neonatal cholestasis.

Methods:  Genotype determination that detects Pi*S and Pi*Z alleles was performed using Elucigene AAT reagents (Cellmark Diagnostics, UK). AAT inclusions were identified by light microscopy using periodic acid‐Schiff (PAS) stain.

Results:  Ninety‐six infants (mean age: 89 days, 48 males) with a history of jaundice since 2 weeks old and a direct bilirubin level >20% of the total were recruited. Only one patient (1 month old, male) was positive for Pi*S allele and 95 were negative for Pi*S and Pi*Z alleles, with an annual incidence of 0.7%. Of the 96, 49 infants underwent diagnostic percutaneous liver biopsy. All liver biopsy specimen were subjected to PAS stain and two infants, 2 and 4 months old, both with idiopathic neonatal hepatitis, had suspicious findings of AAT globules that was confirmed on immunostain. Both infants were negative for Pi*S alleles. The only patient positive for Pi*S allele was negative for PAS globule on liver biopsy.

Conclusion:  Our results showed a low incidence of AAT deficiency caused by the Pi*S and Pi*Z alleles among Filipino infants presenting with neonatal cholestasis, similar to the low carrier rate in the population.
Descriptive epidemiology of small screen recreation among Australian adolescents
Authors: Hardy Louise L , Dobbins Timothy A , Denney‐Wilson Elizabeth A , Okely Anthony D , Booth Michael L
Published: October 2006

Aim:  To describe the epidemiology of small screen recreation (SSR) that is: television, computer, video, and DVD use among school students aged 11–15 years in New South Wales, Australia.

Methods:  Cross‐sectional representative population survey (n = 2750) of 45 primary and 48 secondary schools in rural and urban areas. Self‐reported time spent in SSR was categorised according to national guidelines into less than 2 h per day (low users) or 2 or more hours per day (high users).

Results:  Of primary and secondary school students, 53% and 72%, respectively, were high users of SSR. Boys spent significantly more time in SSR and were more likely to be high users of SSR compared with girls. For primary students, rural boys had a higher prevalence of high SSR use than urban boys (odds ratio (OR) 1.9, 95% confidence interval (CI) 1.0–3.5), while overweight girls had a higher prevalence than healthy‐weight girls (OR 1.8, 95% CI 1.2–2.8). For secondary students, rural boys had a lower prevalence of high SSR use than urban boys (OR 0.5, 95% CI 0.3–0.6), and girls from high SES backgrounds had a lower prevalence than girls from low socio‐economic status backgrounds (OR 0.6, 95% CI 0.3–1.0).

Conclusion:  The majority of school students in New South Wales exceed the national guidelines for SSR. Reducing the time spent in SSR among young people is one potential approach to increasing energy expenditure and reducing adiposity or maintaining a healthy weight. First steps for intervention strategies among school‐age children to reduce SSR could include teaching awareness skills and self‐monitoring techniques.
Atherosclerosis in haemodialysis patients without significant comorbidities: Determinants of progression
Authors: ZUMRUTDAL AYSEGUL , DEMIRCAN SENOL , SEYDAOGLU GULSAH , SINGAN METIN , SEZER SIREN , OZDEMIR F NURHAN , HABERAL MEHMET
Published: October 2006

Aim:  The aim of this prospective study was to assess the determinants of the progression of carotid artery intima‐media thickness (CA‐IMT) for 1 year in haemodialysis (HD) patients without significant comorbidities.

Methods:  Fifty‐four HD patients younger than 55 years, without diabetes, obesity and any clinical evidence of cardiovascular disease (29 men, 25 women; mean age 33.3 ± 10 years; mean time on HD 49.4 ± 43 months) were included in the 1‐year study. CA‐IMT was assessed at baseline and after 12 months. The difference in IMT between these two points of time was calculated (ΔCA‐IMT). C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), haematocrit‐corrected ESR, beta‐2 microglobulin, cardiac troponin I, lipid profile, fibrinogen, homocysteine, CaXP product, intact parathyroid hormone, haematocrit, albumin, uric acid levels, anthropometric parameters (age, body mass index), smoking, hypertension and left ventricular hypertrophy were recorded at baseline.

Results:  The mean value for CA‐IMT at baseline (0.59 ± 0.05 mm) was significantly lower than that at 12 months (0.64 ± 0.07 mm) (P < 0.001). CA‐IMT had increased in 41 patients (75.9%). Age (P = 0.02), CRP (P = 0.03), beta‐2 microglobulin (P = 0.001) and left ventricular hypertrophy (P = 0.01) were independently related with CA‐IMT at baseline. Age (P = 0.003) and CRP (P = 0.04) were the independent variables related with CA‐IMT, measured at 12 months. ΔCA‐IMT correlated positively with age (r = 0.31, P < 0.05). Age and sex were independent predictors of ΔCA‐IMT (R2 for the model 0.56).

Conclusion:  In addition to age and male sex, non‐specific inflammation may have a possible role in the progression of atherosclerosis in HD patients without significant comorbidities.
Roxithromycin inhibits transforming growth factor‐β production by cultured human mesangial cells
Authors: YAMABE HIDEAKI , SHIMADA MICHIKO , KAIZUKA MITSUAKI , NAKAMURA MASAYUKI , KUMASAKA RYUICHIRO , MURAKAMI REI‐ICHI , FUJITA TAKESHI , NAKAMURA NORIO , OSAWA HIROSHI , OKUMURA KEN
Published: October 2006

Background:  Transforming growth factor‐β (TGF‐β) plays an important role in progression of renal injury. However, few materials which inhibit TGF‐β have been known. Roxithromycin (ROX), macrolide antibiotics, is known to have anti‐inflammatory, immunomodulatory and tissue reparative effects besides its bacteriostatic activity, although the exact mechanism of its anti‐inflammatory and immunomodulatory effects was not defined. We examined the effect of ROX on production of TGF‐β and type IV collagen by cultured human mesangial cells (HMC).

Methods:  Human mesangial cells were incubated with several concentrations of ROX and TGF‐β and type IV collagen levels in the culture supernatants were measured by enzyme‐linked immunoassay. Amount of TGF‐β mRNA was also quantified by using a colourimetric mRNA quantification kit and semiquantitative reverse transcriptase polymerase chain reaction. We also examined the effect of ROX on tyrosine kinase, MAP kinase and NF‐κB stimulated by thrombin.

Results:  Roxithromycin (0.1–10.0 µg/mL) inhibited TGF‐β production by HMC in a dose‐ and time‐dependent manner without inducing cell injury. ROX (10.0 µg/mL) also inhibited mRNA expression of TGF‐β in HMC. Thrombin (5 U/mL) stimulated TGF‐β production by HMC and ROX significantly inhibited the stimulating effect of thrombin on TGF‐β production. ROX also inhibited the increment of type IV collagen production stimulated by thrombin. ROX (10.0 µg/mL) suppressed the thrombin‐induced NF‐κB activation, although ROX did not inhibit the activation of tyrosine kinase and MAP kinase by thrombin.

Conclusion:  Roxithromycin has an inhibitory effect on TGF‐β production by HMC possibly via inhibition of NF‐κB. ROX may be a potential agent for the treatment of glomerulosclerosis.
Molecular tumor markers for asbestos‐related mesothelioma: Serum diagnostic markers
Authors: Maeda Masahiro , Hino Okio
Published: October 2006

Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of the tumor may be described as 30–40 years, and the prognosis is dismal. In addition to immunohistochemical markers, recently, serum markers for the diagnosis of mesothelioma have been reported as candidates. In contrast, the expression in renal carcinoma (ERC) gene has been discovered in the Eker rat model (Tsc2 gene mutant), which is a homolog of the human mesothelin/megakaryocyte potentiating factor gene, and a novel ELISA system (N‐ERC/mesothelin) has been developed. It has also been found that N‐ERC/mesothelin is very stable and plentiful in the blood. In the present paper the potential utility of molecular diagnostic markers is reviewed, including ELISA systems for asbestos‐related mesothelioma.
Sparganum mansoni parasitic infection in the lung showing a nodule
Authors: Iwatani Kazunori , Kubota Ichiro , Hirotsu Yasuhiro , Wakimoto Johji , Yoshioka Masakazu , Mori Takeshi , Ito Takaaki , Nomori Hiroaki
Published: October 2006

Reported herein is a 57‐year‐old man infected by Sparganum mansoni, a kind of tapeworm, showing a solitary nodule of the middle lobe of the right lung. Because a transbronchial biopsy could not diagnose the nodule, a right middle lobectomy was performed on suspicion of malignant tumor. The lesion was diagnosed as sparganosis by histological and immuno‐serological examinations. Histological examination revealed granulomatous inflammation with neutrophil and eosinophil infiltration around the worm and interstitial pneumonia surrounding the nodule. Moreover, vasculitis with foreign body giant cell was seen around the lesion. To the authors' knowledge this is the second case of sparganosis limited in the lung, and the current report presents the first detailed histological description of a pulmonary sparganosis case.
Cockayne syndrome with recurrent acute tubulointerstitial nephritis
Authors: Funaki Satoshi , Takahashi Shori , Murakami Hitohiko , Harada Kensuke , Kitamura Hiroshi
Published: October 2006

A 12‐year‐old girl, who had been diagnosed as having Cockayne syndrome (CS), was admitted for emaciation and dehydration. On admission the patient had mild chronic renal failure (glomerular filtration rate: GFR 50 mL/min) and hyperuricemia. After rehydration, allopurinol was commenced for her hyperuricemia. Then, her renal function rapidly deteriorated (GFR 20 mL/min) with enhancement of proximal tubular dysfunction and hypertension. A renal biopsy showed that the patient had acute tubulointerstitial nephritis (ATIN). Based on this diagnosis, allopurinol was stopped and prednisolone was started (2 mg/kg per day), following which the renal tubular function improved. However, the proteinuria intensified to become nephrotic syndrome. After 1 month the patient developed a gastric ulcer. Famotidine was commenced but GFR deteriorated and renal proximal tubular dysfunction re‐occurred. The renal pathology was evaluated by referring to the previous reports of renal pathology in CS. It is suggested that rapid deterioration of the renal function in CS patients might be the result of ATIN. In addition, the present nephrotic syndrome seemed to be accompanied by ATIN, as in other reports.
Non‐cystic solid‐pseudopapillary tumor of the pancreas showing nuclear accumulation and activating gene mutation of β‐catenin
Authors: Nishimori Isao , Kohsaki Takuhiro , Tochika Naoshige , Takeuchi Tamotsu , Minakuchi Tomoko , Okabayashi Takehiro , Kobayashi Michiya , Hanazaki Kazuhiro , Onishi Saburo
Published: October 2006

Solid‐pseudopapillary tumor (SPT) is an unusual pancreatic neoplasm that is characterized by a mixture of solid and cystic components and a fibrous capsule. Recently, the tumorigenesis of SPT has been reported to be associated with gene mutations of β‐catenin, which is a molecule participating in the Wnt signaling pathway. Reported herein is the case of a 53‐year‐old woman with SPT. The tumor, approximately 3 cm in diameter in the pancreas body, had a clear margin and central calcification but had neither a cystic component nor fibrous capsule. Several lines of pathological findings in the surgically resected specimen indicated SPT: (i) pseudopapillary proliferation of eosinophilic polygonal cells with oval nuclei; (ii) positive expression of several marker molecules indicating differentiation into acinar and endocrine cells; and (iii) zymogen granule‐like structures in the cytoplasm on electron microscopy. Further, the tumor cells had intense nuclear accumulation of β‐catenin and an activating mutation, 34Gly(GGA) to Arg(AGA), in exon 3 of the β‐catenin gene, as previously reported in most SPT. These findings suggest that association of the β‐catenin phenotype with development of the rare phenotype of SPT, a non‐cystic and unencapsulated tumor, is unlikely.
Correlation between rheumatoid factor and peripheral eosinophil count in chronic eosinophilic pneumonia
Authors: KUDOU Megumi , YASUBA Hirotaka , KOBAYASHI Yoshiki , HAMADA Kazuyuki , KITA Hideo
Published: October 2006

Abstract:  The relationship between the blood level of rheumatoid factor (RF) and the peripheral blood eosinophil (Eo) count (white blood cells × %Eo, Eo count) in a patient diagnosed with chronic eosinophilic pneumonia was evaluated from before the onset till resolution of the disease. RF levels correlated with Eo counts, and showed a strong correlation with the logarithmic value of the Eo counts (r = 0.816). RF levels tended to become elevated earlier and decline later than Eo counts or abnormal X‐ray shadows. We concluded that the RF level may reflect the activity of this disease. The mechanism of RF elevation in eosinophil‐activated disorders needs to be clarified.
Epithelioid sarcoma presenting as pulmonary cysts with cancer antigen 125 expression
Authors: KIKUCHI Eiki , KINOSHITA Ichiro , YAMAZAKI Koichi , ITOH Tomoo , SHIMIZU Tadamichi , SHIMIZU Hiroshi , NISHIMURA Masaharu
Published: October 2006

Abstract:  A 39‐year‐old Japanese woman presented with a swollen right hand and a right‐sided pneumothorax. Chest CT revealed bilateral multiple pulmonary thin‐walled cysts measuring ≤1 cm in diameter and small nodules. An initial skin biopsy led to a misdiagnosis of metastatic adenocarcinoma, as tumour cells were positive for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen and cancer antigen 125. However, chemotherapy proved ineffective, and the skin biopsy was repeated. A final diagnosis of epithelioid sarcoma (ES) was made. Open lung biopsy showed that the pulmonary nodules represented metastases of ES. Although the pulmonary cyst walls did not contain tumour cells, bronchiolar wall adjacent to the cysts had been infiltrated by tumour cells. These findings suggested that pulmonary cysts, a rare form of pulmonary metastases from soft tissue sarcomas, had developed through a ball‐valve effect of metastatic tumour in small airways. However, presence of cancer antigen 125 hindered obtaining a correct diagnosis of ES.
Systemic antioxidant defences during acute exacerbation of chronic obstructive pulmonary disease
Authors: SADOWSKA Anna M. , LUYTEN Chris , VINTS Anne‐Marie , VERBRAECKEN Johan , RANST Dirk Van , BACKER Wilfried A. De
Published: October 2006

Objective and background:  Existence of an increased oxidative stress has been confirmed in patients with acute exacerbation of COPD. This study aims to examine the extent and time‐course of antioxidant defence in patients with an acute exacerbation of COPD in comparison with stable patients.

Methods:  Twelve patients with acute exacerbation were studied at admission, and then 24 h and 48 h following admission and at discharge. The antioxidants assessed were the endogenous antioxidants: glutathione peroxidase, superoxide dismutase, oxidized and reduced glutathione, albumin and exogenous antioxidants: α‐tocopherol and retinol. Trolox equivalent antioxidant capacity as a marker of antioxidant status was also measured.

Results:  There was an increase in glutathione peroxidase and superoxide dismutase 48 h after admission (P < 0.05). α‐Tocopherol was the lowest 24 h after admission and increased significantly at discharge (P < 0.05).

Conclusions:  There is an increase in antioxidant defence during acute exacerbation of COPD reaching a maximum at 48 h after admission. This rise in the antioxidant defence is not sufficient to prevent depletion of non‐enzymatic antioxidants such as α‐tocopherol.
Effect of a prebiotic‐enriched phytocompound in improving ovalbumin allergenicity
Authors: METUGRIACHUK Yussef , TSUCHIYA Juichiro , MAROTTA Francesco , KAWAKITA Sam , OKURA Ruichi , KUROI Olivia , MINELLI Emilio
Published: October 2006

OBJECTIVE:  The aim of the present study was to test a prebiotic‐phytotherapic compound in an experimental model of oral allergenicity.

METHODS:  Antigen‐specific immunoglobulin E (IgE) elevated mice were prepared by injecting them intraperitoneally with 10 µg of ovalbumin. Subsequently, the mice were exposed to ovalbumin solution intranasally and blood samples were obtained on weekly intervals for 4 weeks to measure serum‐ovalbumin‐specific IgE and total immunoglobulin G. Mice with high titers of ovalbumin‐IgE were intragastrically administered with 0.3 mL of phosphate buffered solution containing either 20 mg of ovalbumin, the same solution with 5 mL of milk, or 20 mg milk added to prebiotic‐phytocompound.

RESULTS:  Ovalbumin administration caused a significant increase of plasma ovalbumin concentration in sensitized mice while prebiotic‐phytocompound‐supplemented mice showed a significantly reduced peak value (P < 0.05). Prebiotic‐phytocompound added to milk exerted a significant effect in lowering the ovalbumin‐IgE level and the total immunoglobulin G level as compared to control plain milk (P < 0.01).

CONCLUSION:  This study provides a rationale basis for a feasible non‐pharmacological therapeutic strategy in food allergen hypersensitivity syndromes.
Abnormal expression of Smurf2 during the process of rat liver fibrosis
Authors: CAI Yu , SHEN Xi Zhong , ZHOU Chao Hui , WANG Ji Yao
Published: October 2006

OBJECTIVE:  Liver fibrosis is a prelude of liver cirrhosis. Currently the molecular mechanism of liver fibrosis is not clear. The purpose of this study is to screen the abnormally expressed genes of liver fibrosis and to illustrate the changes of Smurf2 expression in the process of liver fibrosis.

METHODS:  A liver fibrosis model was established in rats by injection of tetrachlormethane (CCl4). A cDNA microarray analysis was performed on the liver at mid‐stage of fibrosis. Thereafter, a semi‐quantitative RT‐PCR, Western blot analysis and immunohistochemistry test were performed for determining Smurf2, Smad2 and SnoN at week 1, 2, 4 and 8 of establishing the liver fibrosis model.

RESULTS:  Smurf2, FGG, PTAFR, CYP2D6, among others, increased in the fibrosis liver and a semi‐quantitative RT‐PCR confirmed the reliability of the cDNA microarray analysis. Smurf2 in the liver fibrosis model group was at the same level as that of control group at week 1, but decreased at week 2 and 8 and increased at the week 4. Smad2 increased at week 2 and 8 but increased at week 4. However, Smad2 mRNA increased to the same level at week 4 as that at week 2 and 8. The decrease of Smad2 at week 4 may be due to the enhancement of ubiquitination and proteolytic degradation of Smad2 by the increase of Smurf2. SnoN decreased at week 4 and 8 because of the ubiquitination and degradation caused by Smurf2. The decrease of SnoN may explain the progress of liver fibrosis in spite of the decrease of Smad2 at week 4.

CONCLUSION:  This study screened the abnormally expressed genes of liver fibrosis and illustrated the changes of Smurf2, Smad2 and SnoN during the process of liver fibrosis.
CENTRAL PANCREATECTOMY FOR BENIGN PANCREATIC PATHOLOGY/TRAUMA: IS IT A REASONABLE PANCREAS‐PRESERVING CONSERVATIVE SURGICAL STRATEGY ALTERNATIVE TO STANDARD MAJOR PANCREATIC RESECTION?
Authors: Johnson Maria A. , Rajendran Shanmugasundaram , Balachandar Tirupporur G. , Kannan Devy G. , Jeswanth Satyanesan , Ravichandran Palaniappan , Surendran Rajagopal
Published: October 2006

Background:  The aim of this study was to assess the technical feasibility, safety and outcome of central pancreatectomy (CP) with pancreaticogastrostomy or pancreaticojejunostomy in appropriately selected patients with benign central pancreatic pathology/trauma. Benign lesions/trauma of the pancreatic neck and proximal body pose an interesting surgical challenge. CP is an operation that allows resection of benign tumours located in the pancreatic isthmus that are not suitable for enucleation.

Methods:  Between January 2000 and December 2005, eight central pancreatectomies were carried out. There were six women and two men with a mean age of 35.7 years. The cephalic pancreatic stump is oversewn and the distal stump is anastomosed end–to–end with a Roux‐en‐Y jejunal loop in two and with the stomach in six patients. The indications for CP were: non‐functional islet cell tumours in two patients, traumatic pancreatic neck transection in two and one each for insulinoma, solid pseudopapillary tumour, splenic artery pseudoaneurysm and pseudocyst. Pancreatic exocrine function was evaluated by a questionnaire method. Endocrine function was evaluated by blood glucose level.

Results:  Morbidity rate was 37.5% with no operative mortality. Mean postoperative hospital stay was 10.5 days. Neither of the patients developed pancreatic fistula nor required reoperations or interventional radiological procedures. At a mean follow up of 26.4 months, no patient had evidence of endocrine or exocrine pancreatic insufficiency, all the patients were alive and well without clinical and imaging evidence of disease recurrence.

Conclusion:  When technically feasible, CP is a safe, pancreas‐preserving pancreatectomy for non‐enucleable benign pancreatic pathology/trauma confined to pancreatic isthmus that allows for cure of the disease without loss of substantial amount of normal pancreatic parenchyma with preservation of exocrine/endocrine function and without interruption of enteric continuity.
Developmental and regional expression of NADPH‐diaphorase/nitric oxide synthase in spinal cord neurons correlates with the emergence of limb motor networks in metamorphosing Xenopus laevis
Authors: Ramanathan Sankari , Combes Denis , Molinari Micol , Simmers John , Sillar Keith T.
Published: October 2006

Metamorphosis in anuran amphibians requires a complete transformation in locomotor strategy from undulatory tadpole swimming to adult quadrupedal propulsion. The underlying reconfiguration of spinal networks may be influenced by various neuromodulators including nitric oxide, which is known to play an important role in CNS development and plasticity in diverse species, including metamorphosis of amphibians. Using NADPH‐diaphorase (NADPH‐d) staining and neuronal nitric oxide synthase (nNOS) immunofluorescence labelling, the expression and developmental distribution of NOS‐containing neurons in the spinal cord and brainstem were analysed in all metamorphic stages of Xenopus laevis. Wholemount preparations of the spinal cord from early stages of metamorphosis (coincident with emergence of the fore‐ and hindlimb buds) revealed two clusters of NOS‐positive neurons interspersed with areas devoid of stained somata. These cells were distributed in three topographic subgroups, the most ventral of which had axonal projections that crossed the ventral commissure. Motoneurons innervating the fore‐ and hindlimb buds were retrogradely labelled with horseradish peroxidase (HRP) to determine their position in relation to the two NOS‐expressing cord regions. Limb motoneurons and NOS‐positive cells did not overlap, indicating that during early stages of metamorphosis nitrergic neurons are excluded from regions where spinal limb circuits are forming. As metamorphosis progresses, NOS expression became distributed along the length of the spinal cord together with an increase in the number and intensity of labelled cells and fibers. NOS expression reached a peak as the forelimbs emerge then declined. These findings are consistent with a role for nitric oxide (NO) in the developmental transition from undulatory swimming to quadrupedal locomotion.
Persistent penetration of MPTP through the nasal route induces Parkinson's disease in mice
Authors: Rojo Ana I. , Montero Celia , Salazar María , Close Ryan M. , Fernández‐Ruiz Javier , Sánchez‐González Miguel A. , De Sagarra María Rosa , Jackson‐Lewis Vernice , Cavada Carmen , Cuadrado Antonio
Published: October 2006

The aetiology of idiopathic Parkinson's disease (PD) is poorly defined but environmental aggressions may be relevant. Here, we report a new model of PD in mice, based on chronic inoculation with neurotoxins in the nasal cavity, which is a natural route of contact with the environment. C57BL/6 mice, submitted to daily intranasal inoculation with MPTP for 30 days, developed motor deficits that correlated with a progressive and severe depletion of striatal dopamine levels, and loss of tyrosine hydroxylase and dopamine transporter staining in substantia nigra and striatum. Moreover, mice intranasally inoculated with MPTP developed strong astrogliosis and microgliosis in substantia nigra and striatum. Consistent with these observations, a role for oxidant aggression was demonstrated by increased levels of Mn‐superoxide dismutase. However, α‐synuclein aggregation was not observed. This new animal model provides a new tool for studying PD symptoms that develop slowly over time, and it may be used to asses risk from environmental neurotoxins.
Effects of hypocretin‐1 in 192‐IgG–saporin‐lesioned rats
Authors: Blanco‐Centurion Carlos A. , Shiromani Anjelica , Winston Elizabeth , Shiromani Priyattam J.
Published: October 2006

Hypocretin, also known as orexin, is a neuropeptide located in the perifornical region of the lateral hypothalamus; this region projects to all the major arousal centres including the basal forebrain. The basal forebrain contains a mixed population of neurons, some of which are cholinergic. To identify the relative contribution of the noncholinergic neurons to arousal, here we utilized 192‐IgG–saporin to lesion the basal forebrain cholinergic neurons and determine whether microinjection of hypocretin‐1 to the basal forebrain is still effective in inducing arousal. In Sprague–Dawley rats given 192‐IgG–saporin (intraventricular, 6 µg; n = 7) 92% of the basal forebrain cholinergic neurons were destroyed compared to nonlesioned rats (n = 5). In the lesioned rats microinjection of hypocretin‐1 (0.0625, 0.125 or 0.25 nmol in 250 nL) to the basal forebrain increased waking and suppressed sleep (both non‐REM and REM) in a concentration‐dependent manner and to the same extent as in nonlesioned rats. These results suggest that, in the absence of the basal forebrain cholinergic neurons, the basal forebrain noncholinergic neurons are able to convey hypocretin's arousal signal unabated.
Florivory: the intersection of pollination and herbivory
Authors: McCall Andrew C. , Irwin Rebecca E.
Published: October 2006

Plants interact with many visitors who consume a variety of plant tissues. While the consequences of herbivory to leaves and shoots are well known, the implications of florivory, the consumption of flowers prior to seed coat formation, have received less attention. Herbivory and florivory can yield different plant, population and community outcomes; thus, it is critical to distinguish between these two types of consumption. Here, we consider the ecological and evolutionary consequences of florivory. A growing number of studies recognize that florivory is common in natural systems and in some cases surpasses leaf herbivory in magnitude and impact. Florivores can affect male and female plant fitness via direct trophic effects and through altered pathways of species interactions. In particular, florivory can affect pollination and have consequences for plant mating and floral sexual system evolution. Plants are not defenceless against florivore damage. Concepts of resistance and tolerance can be applied to plant–florivore interactions. Moreover, extant theories of plant chemical defence, including optimal defence theory, growth rate hypothesis and growth differentiation–balance hypothesis, can be used to make testable predictions about when and how plants should defend flowers against florivores. The majority of the predictions remain untested, but they provide a theoretical foundation on which to base future experiments. The approaches to studying florivory that we outline may yield novel insights into floral and defence traits not illuminated by studies of pollination or herbivory alone.
Expected earnings growth and the cost of capital: an analysis of accounting regime change in the European financial market
Authors: Dargenidou Christina , McLeay Stuart , Raonic Ivana
Published: October 2006

This study focuses on the relation between the cost of equity capital and earnings expectations when the properties of accounting that determine earnings vary across different regulatory regimes. More particularly, it addresses the European setting where different types of GAAP regime have continued to function in the presence of the gradual harmonization of the underlying legal framework, and where the adoption of internationally recognized accounting standards by certain firms has anticipated the requirement for International Financial Reporting Standards. On the basis of estimates of the cost of equity that are implied by analysts’ earnings forecasts, the article provides evidence that financial market integration may have already contributed to mitigating the economic consequences of accounting diversity, and that switching to IFRS could have a short lived impact on capital markets. Moreover, based on firm level transparency and disclosure rankings provided by Standard and Poor's, it is shown how the quality of financial reporting conditions the implied cost of equity under different GAAP.
Factors Affecting European Farmers' Participation in Biodiversity Policies
Authors: Siebert Rosemarie , Toogood Mark , Knierim Andrea
Published: October 2006

This article reports the major findings from an interdisciplinary research project that synthesises key insights into farmers' willingness and ability to co‐operate with biodiversity policies. The results of the study are based on an assessment of about 160 publications and research reports from six EU member states and from international comparative research. We developed a conceptual framework to systematically review the existent literature relevant for our purposes. This framework provides a common structure for analysing farmers' perspectives regarding the introduction into farming practices of measures relevant to biodiversity. The analysis is coupled and contrasted with a survey of experts. The results presented above suggest that it is important to view support for practices oriented towards biodiversity protection not in a static sense – as a situation determined by one or several influencing factors – but rather as a process marked by interaction. Financial compensation and incentives function as a necessary, though clearly not sufficient condition in this process.
COMPLEMENTARITY BETWEEN LOCAL KNOWLEDGE AND INTERNATIONALIZATION IN REGIONAL TECHNOLOGICAL PROGRESS*
Authors: López‐Bazo Enrique , Requena Francisco , Serrano Guadalupe
Published: October 2006

ABSTRACT Trade, foreign direct investment, and inter‐regional R&D spillovers facilitate competition, the spread of knowledge, and the adoption of more advanced technologies, which in turn hastens total factor productivity (TFP) growth. The spread of these efficiency gains from internationalization requires a sufficient local knowledge to enable them to be adapted to the domestic productive environment. Thus, higher local knowledge and internationalization will lead to TFP growth, and the greater the complementarity between variables the higher the TFP growth. We test the complementarity hypothesis using Spanish regional data over the period 1980–1995 in which both regional local knowledge and internationalization experienced a notable increase.
SOMETIMES CLOSE IS GOOD ENOUGH: THE VALUE OF NEARBY ENVIRONMENTAL AMENITIES*
Authors: Schmidt Lucie , Courant Paul N.
Published: October 2006

ABSTRACT An extensive empirical literature exists, showing that variations in region‐specific amenities can account for persistent differences in real wages across regions. However, this literature has considered only amenities in the same location as the household. This paper argues that environmental amenities at some distance from but accessible to urban areas may lead to negative compensating wage differentials. We use a general equilibrium framework and data from the 1995 Current Population Survey to calculate implicit amenity prices based on measures of distance to environmental amenities. Our results suggest that amenities outside the metropolitan area do generate compensating wage differentials, as workers are willing to accept lower wages to live in accessible proximity to “nice” places. This implies that these places provide a positive externality to those communities that find them accessible. The estimated effects are quantitatively important, suggesting that these externalities should be taken into account in policy making.
A SPATIAL ANALYSIS OF SECTORAL VARIATIONS IN RETURNS TO EXTERNAL SCALE
Authors: Hanink Dean M.
Published: October 2006

ABSTRACT This paper reports results of spatially explicit analyses of external scale effects across a variety of sectors, including manufacturing. Using data from New England counties, earnings are found to exhibit increasing returns to urbanization in every sector. Returns to sectoral localization are mixed, however, with increasing returns in one sector, constant returns in five sectors, and decreasing returns in two sectors. External scale effects are fairly confined in their spatial extent, with only retailing and services particularly marked by spillover effects from neighboring counties.