bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed cardioprotection with isoflurane: role of reactive oxygen and nitrogen
Authors: Shi Yang , Hutchins William C. , Su Jidong , Siker Daniel , Hogg Neil , Pritchard Kirkwood A. , Keszler Agnes , Tweddell James S. , Baker John E.
Published: September 2004

We determined whether isoflurane can confer delayed cardioprotection in the adult rat by triggering increased production of reactive oxygen (ROS) and nitrogen species (RNS). Our objectives were to determine 1) the concentration of isoflurane that confers delayed cardioprotection in the adult rat, 2) the role of ROS and RNS in the induction of delayed cardioprotection, and 3) the cellular sources of ROS and RNS responsible for induction of delayed cardioprotection by isoflurane. Male Sprague-Dawley rats at 8 wk of age ( n = 8 rats/group) were exposed to 0.5%, 0.8%, 1%, and 2% (vol/vol) isoflurane-100% oxygen for 2 h. Isoflurane conferred delayed cardioprotection 24 h later at a concentration of 0.8% (vol/vol). Administration of manganese (III) tetrakis (4-benzoic acid)porphyrin chloride (MnTBAP), a superoxide scavenger (15 mg/kg ip), or NG-nitro-l-arginine methyl ester (l-NAME), a general nitric oxide synthase inhibitor (15 mg/kg ip), 15 min before isoflurane treatment abolished the delayed cardioprotective effects of isoflurane. MnTBAP and l-NAME had no effect on delayed cardioprotection in untreated hearts. Perfusion of isolated hearts with hydroethidine, a fluorescent probe for superoxide, after isoflurane treatment resulted in a twofold increase in ethidine staining of isoflurane-treated hearts compared with untreated controls, which was attenuated by myxothiazol, an inhibitor of the mitochondrial electron transport chain (0.2 mg/kg ip) and l-NAME (15 mg/kg ip). Nitrite and nitrate content in isoflurane-treated hearts was 1.5-fold higher than in untreated hearts, whereas myocardial reduced glutathione levels were decreased by 13% in 0.8% but not in 1.0% isoflurane-treated hearts. We conclude that isoflurane confers delayed cardioprotection in the adult rat, triggered by ROS and RNS.
Cyclooxygenase- and lipoxygenase-dependent relaxation to arachidonic acid in rabbit small mesenteric arteries
Authors: Zhang David X. , Gauthier Kathryn M. , Chawengsub Yuttana , Holmes Blythe B. , Campbell William B.
Published: September 2004

We recently reported that the lipoxygenase product 11,12,15-trihydroxyeicosatrienoic acid (THETA) mediates arachidonic acid (AA)-induced relaxation in the rabbit aorta. This study was designed to determine whether this lipoxygenase metabolite is involved in relaxation responses to AA in rabbit small mesenteric arteries. AA (10−9–10−4 M) produced potent relaxations in isolated phenylephrine-preconstricted arteries, with a maximal relaxation of 99 ± 0.5% and EC50 of 50 nM. The cyclooxygenase (COX) inhibitors indomethacin (10 μM), NS-398 (10 μM, selective for COX-2), and SC-560 (100 nM, selective for COX-1) caused a marked rightward shift of concentration responses to AA. With the use of immunohistochemical analysis, both COX-1 and COX-2 were detected in endothelium and smooth muscle of small mesenteric arteries. Indomethacin-resistant relaxations were further reduced by the lipoxygenase inhibitors cinnamyl-3,4-dihydroxy-cyanocinnamate (CDC; 1 μM), nordihydroguaiaretic acid (NDGA; 1 μM), and ebselen (1 μM). HPLC analysis showed that [14C]AA was metabolized by mesenteric arteries to PGI2, PGE2, THETAs, hydroxyepoxyeicosatrienoic acids (HEETAs), and 15-hydroxyeicosatetraenoic acid (15-HETE). The production of PGI2 and PGE2 was blocked by indomethacin, and the production of THETAs, HEETAs, and 15-HETE was inhibited by CDC and NDGA. Column fractions corresponding to THETAs were further purified, analyzed by gas chromatography/mass spectrometry, and identified as 11,12,15- and 11,14,15-THETA. PGI2, PGE2, and purified THETA fractions relaxed mesenteric arteries precontracted with phenylephrine. The AA- and THETA-induced relaxations were blocked by high K+ (60 mM). These findings provide functional and biochemical evidence that AA-induced relaxation in rabbit small mesenteric arteries is mediated through both COX and lipoxygenase pathways.
Concurrent opposite effects of trichostatin A, an inhibitor of histone deacetylases, on expression of α-MHC and cardiac tubulins: implication for gain in cardiac muscle contractility
Authors: Davis Francesca J. , Pillai Jyothish B , Gupta Madhu , Gupta Mahesh P.
Published: September 2004

Histone deacetylases (HDACs) are a family of enzymes that catalyze the removal of acetyl groups from core histones, resulting in change of chromatin structure and gene transcription activity. In the heart, HDACs are targets of hypertrophic signaling, and their nonspecific inhibition by trichostatin A (TSA) attenuates hypertrophy of cultured cardiac myocytes. In this study, we examined the effect of TSA on two major determinants of cardiac contractility: α-myosin heavy chain (MHC) expression and microtubular composition and organization. TSA upregulated the expression of α-MHC in cultured cardiac myocytes, as well as in an in vivo model of hypothyroid rats. Studies designed to delineate mechanisms of α-MHC induction by TSA revealed an obligatory role of early growth response factor-1 on activation of the α-MHC promoter. Concurrently, TSA downregulated the expression of α- and β-tubulins and prevented the induction of tubulins by a hypertrophy agonist, ANG II. The ANG II-mediated increased proportion of α- and β-tubulins associated with polymerized microtubules was also markedly reduced after treatment of cells by TSA. Results obtained from immunofluorescent microscopy indicated that TSA had no noticeable effect on the organization of cardiac microtubules in control cells, whereas it prevented the ANG II-induced dense parallel linear arrays of microtubules to a profile similar to that of controls. Together, these results demonstrate that inhibition of HDACs by TSA regulates the cardiac α-MHC and tubulins in a manner predictive of improved cardiac contractile function. These studies improve our understanding of the role of HDACs on cardiac hypertrophy with implications in development of new therapeutic agents for treatment of cardiac abnormalities.
Cardiac function in hearts isolated from a rat model deficient in mast cells
Authors: Kennedy Richard H. , Hauer-Jensen Martin , Joseph Jacob
Published: September 2004

Several studies have examined the role of mast cells in the myocardial response to injury such as that caused by hypertension and ischemia-reperfusion. However, little is known about the influence of mast cells on normal myocardial structure and function. The present experiments examined cardiac function in Langendorff-perfused hearts isolated from 6- and 9-mo-old male mast cell-deficient ( Ws/ Ws) and mast cell-competent rats. A fluid-filled balloon catheter was used to measure left ventricular diastolic and systolic function at increasing preload volumes. At 6 mo of age, mast cell-deficient rats showed a slight cardiac hypertrophy (as monitored by heart weight and heart weight-to-body weight ratio) but no significant change in maximum observed systolic or diastolic function. In contrast, at 9 mo of age, the mast cell-deficient group showed no signs of hypertrophy but displayed a diastolic dysfunction characterized by decreased compliance without a significant decline in maximum observed basal −dP/d tmax. There were no significant differences in maximum observed values for measures of systolic function (developed pressure and +dP/d tmax). In summary, the results of this study in adult rats suggest that mast cells influence cardiac function in the absence of injury and that observed differences between mast cell-competent and -deficient animals vary with age. Thus it is important to consider these “physiological” actions and resulting changes in function when studying effects of insult in mast cell-deficient models.
Freshly isolated rat alveolar type I cells, type II cells, and cultured type II cells have distinct molecular phenotypes
Authors: Gonzalez Robert , Yang Yee Hwa , Griffin Chandi , Allen Lennell , Tigue Zachary , Dobbs Leland
Published: September 2004

We used microarray analysis with Affymetrix rat chips to determine gene expression profiles of freshly isolated rat type I (TI) and TII cells and cultured TII cells. Our goals were 1) to describe molecular phenotypic “fingerprints” of TI and TII cells, 2) to gain insight into possible functional differences between the two cell types through differentially expressed genes, 3) to identify genes that might indicate potential functions of TI cells, since so little is known about this cell type, and 4) to ascertain the similarities and differences in gene expression between cultured TII cells and freshly isolated TI cells. For these experiments, we used preparations of isolated TI and TII cells that contained <2% cross-contamination. With a false discovery rate of 1%, 601 genes demonstrated over twofold different expression between TI and TII cells. Those genes with very high levels of differential expression may be useful as markers of cell phenotype and in generating novel hypotheses about functions of TI and TII cells. We found similar numbers of differentially expressed genes between freshly isolated TI or TII cells and cultured TII cells (698, 637 genes) and freshly isolated TI and TII cells (601 genes). Tests of sameness/difference including cluster dendrograms and log/log identity plots indicated major differences between the phenotypes of freshly isolated TI cell and cultured type II cell populations. The latter results suggest that experiments with TII cells cultured under these conditions should be interpreted with caution with respect to biological relevance to TI or TII cells.
Distinct PKC isoforms mediate cell survival and DNA synthesis in thrombin-induced myofibroblasts
Authors: Bogatkevich Galina S. , Gustilo Estella , Oates Jim C. , Feghali-Bostwick Carol , Harley Russell A. , Silver Richard M. , Ludwicka-Bradley Anna
Published: September 2004

Thrombin activates protease-activated receptor (PAR)-1 and induces a myofibroblast phenotype in normal lung fibroblasts that resembles the phenotype of scleroderma lung fibroblasts. We now demonstrate that PAR-1 expression is dramatically increased in lung tissue from scleroderma patients, where it is associated with inflammatory and fibroproliferative foci. We also observe that thrombin induces resistance to apoptosis in normal lung fibroblasts, and this process is regulated by protein kinase C (PKC)-ε but not by PKC-α. Overexpression of a constitutively active (c-a) form of PAR-1 or PKC-ε significantly inhibits Fas ligand-induced apoptosis in lung fibroblasts, whereas scleroderma lung fibroblasts are resistant to apoptosis de novo. Thrombin translocates p21Cip1/WAF1, a signaling molecule downstream of PKC, from the nucleus to cytoplasm in normal lung fibroblasts mimicking the localization of p21Cip1/WAF1 in scleroderma lung fibroblasts. Overexpression of c-a PKC-α or PKC-ε results in accumulation of p21Cip1/WAF1 in the cytoplasm. Depletion of PKC-α or inhibition of mitogen-activated protein kinase (MAPK) blocks thrombin-induced DNA synthesis in lung fibroblasts. Inhibition of PKC by calphostin or PKC-α, but not PKC-ε, by antisense oligonucleotides prevents thrombin-induced MAPK phosphorylation and accumulation of G1 phase regulatory protein cyclin D1, suggesting that PKC-α, MAPK, and cyclin D1 mediate lung fibroblast proliferation. These data demonstrate that two distinct PKC isoforms mediate thrombin-induced resistance to apoptosis and proliferation and suggest that p21Cip1/WAF1 promotes both phenomena.
Estrogen’s attenuating effect on the exercise pressor reflex is more opioid dependent in gonadally intact than in ovariectomized female cats
Authors: Schmitt Petra M. , Kaufman Marc P.
Published: September 2004

Using gonadally intact female cats, we showed previously that estrogen, applied topically to the spinal cord, attenuated the exercise pressor reflex. Although the mechanism by which estrogen exerted its attenuating effect is unknown, this steroid hormone has been shown to influence spinal opioid pathways, which in turn have been implicated in the regulation of the exercise pressor reflex. These findings prompted us to test the hypothesis that opioids mediate the attenuating effect of estrogen on the exercise pressor reflex in both gonadally intact female and ovariectomized cats. We therefore applied 200 μl of 17β-estradiol (0.01 μg/ml) with and without the addition of 1,000 μg naloxone, a μ- and δ-opioid antagonist, to a spinal well covering the L6–S1 spinal cord in decerebrated female cats that were either gonadally intact or ovariectomized. The exercise pressor reflex was evoked by electrical stimulation of the L7 or S1 ventral root, a maneuver that caused the hindlimb muscles to contract statically. We found that, in gonadally intact cats, the attenuating effect of estrogen was more pronounced than that in ovariectomized cats. We also found that, in gonadally intact female cats, naloxone partly reversed the attenuation of the pressor response to static contraction caused by spinal estrogen application. For example, in intact cats, the pressor response to contraction before estrogen application averaged 39 ± 4 mmHg ( n = 10), whereas the pressor response 60 min afterward averaged only 18 ± 4 mmHg ( P < 0.05). In contrast, the pressor response to contraction before estrogen and naloxone application averaged 33 ± 5 mmHg ( n = 11), whereas afterward it averaged 27 ± 6 mmHg ( P < 0.05). In ovariectomized cats, naloxone was less effective in reversing the attenuating effect of estrogen on the exercise pressor reflex.
Nonuniform effects of endurance exercise training on vasodilation in rat skeletal muscle
Authors: McAllister R. M. , Jasperse J. L. , Laughlin M. H.
Published: September 2004

Endurance exercise training (Ex) has been shown to increase maximal skeletal muscle blood flow. The purpose of this study was to test the hypothesis that increased endothelium-dependent vasodilation is associated with the Ex-induced increase in muscle blood flow. Furthermore, we hypothesized that enhanced endothelium-dependent dilation is confined to vessels in high-oxidative muscles that are recruited during Ex. To test these hypotheses, sedentary (Sed) and rats that underwent Ex (30 m/min × 10% grade, 60 min/day, 5 days/wk, 8–12 wk) were studied using three experimental approaches. Training effectiveness was evidenced by increased citrate synthase activity in soleus and vastus lateralis (red section) muscles ( P < 0.05). Vasodilatory responses to the endothelium-dependent agent acetylcholine (ACh) in situ tended to be augmented by training in the red section of gastrocnemius muscle (RG; Sed: control, 0.69 ± 0.12; ACh, 1.25 ± 0.15; Ex: control, 0.86 ± 0.17; ACh, 1.76 ± 0.27 ml·min−1·100 g−1·mmHg−1; 0.05 < P < 0.10 for Ex vs. Sed during ACh). Responses to ACh in situ did not differ between Sed and Ex for either the soleus muscle or white section of gastrocnemius muscle (WG). Dilatory responses of second-order arterioles from the RG in vitro to flow (4–8 μl/min) and sodium nitroprusside (SNP; 10−7 through10−4 M), but not ACh, were augmented in Ex (vs. Sed; P < 0.05). Dilatory responses to ACh, flow, and SNP of arterioles from soleus and WG muscles did not differ between Sed and Ex. Content of the endothelial isoform of nitric oxide synthase (eNOS) was increased in second-order, fourth-order, and fifth-order arterioles from the RG of Ex; eNOS content was similar between Sed and Ex in vessels from the soleus and WG muscles. These findings indicate that Ex induces endothelial adaptations in fast-twitch, oxidative, glycolytic skeletal muscle. These adaptations may contribute to enhanced skeletal muscle blood flow in endurance-trained individuals.
Imaging of the Liver by Helical CT and MR Imaging
Authors: Yamashita Yasuyuki , Morishita Shoji , Awai Kazuo , Kawanaka Koichi
Published: September 2004

With modern imaging technologies, including helical CT and MR imaging, the evaluation of liver morphology, blood flow and detection and characterization of liver neoplasms is possible in a noninvasive manner. Experiences in numerous institutions have established that both imaging methods are highly accurate in diagnosing hepatic pathology. Three-dimensional evaluation is feasible with fast imaging techniques such as multislice CT. With tissue-specific MR contrast agents such as SPIO, our capability is enhanced not only with respect to lesion detection but also lesion characterization.
Imaging Diagnosis of Cirrhosis and Chronic Hepatitis
Authors: Ito Katsuyoshi , Mitchell Donald G.
Published: September 2004

Cirrhosis is an end stage of chronic diffuse liver disease, characterized by irreversible hepatic fibrosis. Cirrhosis slowly progresses from chronic hepatitis to early cirrhosis and finally to advanced cirrhosis with the increasing risk of complications, and causes regional morphologic changes of the liver during the course of the disease, according to disease severity. MR imaging is better able to provide comprehensive information about cirrhosis or chronic hepatitis and their complications than any other imaging modality currently available. In this article, we reviewed the spectrum of imaging findings of cirrhosis and chronic hepatitis, including regional changes of hepatic morphology, several signs of early and advanced cirrhosis, nodular liver surface, hepatic iron deposition, regenerative nodules, and varices and portosystemic collaterals.
Detection of Intratumoral Vascularity in Small Hepatocellular Carcinoma by Coded Phase Inversion Harmonics
Authors: Wen Yan Ling , Zhou Pei , Kudo Masatoshi
Published: September 2004

Objective: To investigate the value of contrast-enhanced coded phase inversion harmonic imaging (PIHI) in the depiction of intratumoral vascularity in small hepatocellular carcinoma (HCC). Methods: Eighty-five patients with 106 HCCs ≤3 cm in diameter were evaluated with coded harmonic angio (CHA), a coded PIHI, with use of an intravenous contrast medium, Levovist. Intratumoral vessels were detected in the early arterial phase, and tumor parenchymal stain was demonstrated in the late vascular phase. The detectability of intratumoral vascularity on contrast-enhanced CHA was compared with that on dynamic computed tomography (CT) and digital subtraction angiography (DSA). Results: With a combination of both vessel images and parenchymal flow images demonstrated by contrast-enhanced CHA, 98 of 106 small HCCs were evaluated as being hypervascular or isovascular. Using the results on dynamic CT as a gold standard, the sensitivity, specificity and accuracy were 95.1, 100 and 95.3%, respectively. The detection rate of intratumoral vascularity by contrast-enhanced CHA was 92.5% (98/ 106), compared with 97.2% (103/106) on dynamic CT (p = 0.14) and 88.9% (40/45) on DSA (p = 0.53). Conclusions: Contrast-enhanced coded PIHI is a sensitive tool for depicting intratumoral vascularity of small HCC.
Imaging of Dysplastic Nodules and Small Hepatocellular Carcinomas: Experience with Explanted Livers
Authors: Krinsky Glenn
Published: September 2004

Differentiation of benign from malignant nodules in the end-stage cirrhotic liver can be challenging, due to the presence of fibrosis, necrosis and altered blood supply. Whole liver explant pathologic correlation provides a unique opportunity to evaluate the sensitivity and specificity of current imaging modalities for the diagnosis of HCC and dysplastic nodules in the cirrhotic liver. This chapter will explore and critique the imaging literature with an emphasis on studies performed with timely explanted liver correlation.
Multidetector Row CT and MR Imaging in Diagnosing Hepatocellular Carcinoma
Authors: Murakami Takamichi , Hori Masatoshi , Kim Tonsok , Kawata Shuji , Abe Hisashi , Nakamura Hironobe
Published: September 2004

It is important to diagnose hepatocellular carcinoma (HCC) correctly and in early stage, because viral hepatitis and liver cirrhosis are often complicated by HCC. Noncontrast and enhanced CT and MRI are very useful to visualize and diagnose HCC objectively. Especially, CT and MR imaging with dynamic study is essential to diagnose HCC, because it is usually hypervascular. Dynamic CT and MR study also improve differential diagnosis in the characterization of the tumor. However, to perform useful dynamic study, it is necessary to use a CT unit which can make a helical scan, or a MR system with fast imaging technique available that can obtain more than 15 slices within a single breath hold. Tissue specific contrast medium, such as superparamagnetic iron oxide that is available only on MRI, is also useful for diagnosis of HCC.
Pitfalls in the Imaging Diagnosis of Hepatocellular Nodules in the Cirrhotic and Noncirrhotic Liver
Authors: Yoshimitsu Kengo , Irie Hiroyuki , Aibe Hitoshi , Tajima Tsuyoshi , Nishie Akihiro , Asayama Yoshiki , Matake Kunishige , Nakayamka Tomohiro , Kakihara Daisuke , Honda Hiroshi
Published: September 2004

Contrast-enhanced CT and MR are the most commonly used modalities for objective evaluation of hepatocellular nodules. Various types of pseudolesions as seen on CT or MR have been reported, which are attributable to either focal alteration in hemodynamics or parenchymal metabolism, or to both. Pseudolesions specifically seen in cirrhotic liver include arterio-portal shunt, regenerating or hyperplastic nodules, and confluent fibrosis. In noncirrhotic liver, transient focal compression to the liver, third inflow other than normal hepatic arterial and portal venous flow, and vessel compromise are the causes of pseudolesions. To understand the characteristic features of these pseudolesions, and their underlying mechanism as well, is important for proper diagnosis of true hepatocellular lesions.
Imaging of Multistep Human Hepatocarcinogenesis by CT during Intra-Arterial Contrast Injection
Authors: Matsui Osamu
Published: September 2004

Various types of hepatocellular nodules are seen in cirrhotic livers. In these nodules, two types of human hepatocarcinogenesis are now considered. One is de novo hepatocarcinogenesis and the other is the stepwise development from high-grade dysplastic nodule (DN), high-grade DN with well-differentiated HCC foci, and overt HCC. According to our analysis by CT during arterial portography (CTAP) and CT during hepatic arteriography (CTHA) and histological study, in accordance with the elevation of the grade of malignancy of the nodules, the portal tract including normal portal vein (intranodular portal supply) and hepatic artery (intranodular arterial supply through normal hepatic arteries) are decreased. On the other hand, abnormal artery (intranodular arterial supply through newly formed abnormal arteries) gradually increases. Therefore, we can estimate the grade of malignacy of the nodules from intranodular blood supply. To know this blood supply pattern is important for the early detection, characterization and treatment of early stage HCCs. We also revealed that there was a close correlation between the prognosis of the nodules and the blood supply patterns.
FLEP Chemotherapy for α-Fetoprotein-Producing Gastric Cancer
Authors: Kochi Mitsugu , Fujii Masashi , Kaiga Teruo , Takahashi Toru , Morishita Yukie , Kobayashi Michiyo , Kasakura Yuichi , Takayama Tadatoshi
Published: September 2004

Objective: This study aimed at comparing the efficacy of FLEP chemotherapy in the treatment of stage IV AFP-producing gastric cancer and stage IV non-AFP-producing gastric cancer. Methods: Between 1989 and 2002, 57 patients with stage IV inoperable gastric cancer were given a combination of chemotherapy with 5-fluorouracil (5-FU), leucovorin (LV), etoposide (VP-16) and cis-diamminedichloroplatinum (CDDP) (designated as FLEP). In the two groups classified histologically according to AFP positivity, the rate of response and conversion to surgery, disease-free and overall survival were compared. The disease-free and overall survival in the two groups was compared by a log-rank test. Results: Patients of the AFP-producing group had a significantly better response rate (70 vs. 31.9%, p = 0.03) and a better conversion rate (40 vs. 12.8%, p = 0.04) than those of the non-AFP-producing group. Patients of the AFP-producing group also had a significantly better disease-free and overall survival (p = 0.02) than those of the non-AFP-producing group. AFP-producing gastric cancer was identified as an independent prognostic factor. Conclusion: FLEP chemotherapy was more effective for stage IV AFP-producing gastric cancer than in stage IV non-AFP-producing gastric cancer. Preoperative FLEP chemotherapy improved the prognosis of AFP-producing gastric cancer because of downstaging.
Coexpression of Gas6/Axl in Human Ovarian Cancers
Authors: Sun Wenshu , Fujimoto Jiro , Tamaya Teruhiko
Published: September 2004

Objectives: Gas6, the protein product of the growth arrest-specific gene 6 (gas6), a member of the vitamin K-dependent protein family, was identified as a ligand for the Axl/Sky family of receptor tyrosine kinases. The aim is to study for the presence of Gas6 and its receptor Axl and Sky related to specific growth in the ovarian cancers, and to evaluate their plausible growth potential and mechanism. Methods: In ovarian cancers of 90 cases, the histoscores and mRNA levels of Gas6, Axl and Sky were determined by immunohistochemistry and competitive reverse transcription-polymerase chain reaction-Southern blot analysis using the recombinant RNA, respectively. Results: The histoscores and mRNA levels of Gas6 and Axl in ovarian cancers were significantly higher than in normal ovaries, regardless of histopathological type or clinical stage of ovarian cancers. Conclusions: Gas6/Axl pathway could play a role in the complex events taking place during the early changes of ovarian cancer progression.
Translocation t(11;18)(q21;q21) Is Not Predictive of Response to Chemotherapy with 2CdA in Patients with Gastric MALT Lymphoma
Authors: Streubel Berthold , Ye Hongtao , Du Ming-Qing , Isaacson Peter G. , Chott Andreas , Raderer Markus
Published: September 2004

Background: t(11;18)(q21;q21) resulting in the API2-MALT1 fusion transcript is an exclusive finding in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). While it has recently been demonstrated as a negative predictor for gastric MALT lymphoma undergoing eradication of Helicobacter pylori, nothing is known about the relation between t(11;18)(q21;q21) status and response to chemotherapy. We have therefore performed a retrospective analysis of t(11;18)(q21;q21) in patients undergoing chemotherapy with the nucleoside analogue cladribine (2CdA) for gastric MALT lymphoma. Patients and Methods: Eighteen cases of gastric MALT lymphoma treated with 2CdA were reviewed, and 17 could be investigated for t(11;18)(q21;q21) by reverse-transcription polymerase chain reaction and fluorescence in situ hybridization. t(11;18)(q21;q21) was correlated with response to chemotherapy. Results: Of the 17 patients with gastric MALT lymphoma treated with 2CdA, 9 were at stage IE, 2 at stage IIE and 6 at stage IV. Eight cases with stage IE lymphoma were first treated with H. pylori eradication, but none of them showed histological regression during a minimum follow-up of 12 months, and they were subsequently treated with primary chemotherapy. One patient received chemotherapy due to absence of H. pylori infection. Another patient initially rated as stage IE whose gastric lymphoma did not respond developed spread to the lung during follow-up after eradication. All the remaining 13 cases were treated by chemotherapy at the time of diagnosis. Out of these 17, 8 patients (47%) were found to carry t(11;18)(q21;q21). One patient, who was negative for t(11;18)(q21;q21), progressed during chemotherapy and died 5 months after initiation of treatment. One patient each with and without t(11;18)(q21; q21) had a partial response lasting for 14 and >18 months, respectively. One t(11;18)(q21;q21)-positive patient had stable disease for >16 months. The remaining patients achieved a complete remission (CR) following treatment; 6 were positive for t(11;18)(q21;q21), while the remaining 6 were negative. Two patients [1 positive and 1 negative for t(11;18)(q21;q21), respectively] have developed a local relapse following CR and were salvaged by radiotherapy. Conclusion: Our findings suggest that the presence of the API2-MALT1 fusion transcript resulting from t(11;18)(q21;q21) does not adversely affect the response of gastric MALT lymphoma to chemotherapy with 2CdA. 2CdA appears to be an attractive agent for treatment of gastric MALT lymphoma unresponsive to H. pylori eradication, including those positive for t(11;18)(q21;q21).
Cell Growth Inhibition and Gene Expression Induced by the Histone Deacetylase Inhibitor, Trichostatin A, on Human Hepatoma Cells
Authors: Chiba Tetsuhiro , Yokosuka Osamu , Fukai Kenichi , Kojima Hiroshige , Tada Motohisa , Arai Makoto , Imazeki Fumio , Saisho Hiromitsu
Published: September 2004

Objective: Histone deacetylase (HDAC) inhibitors have been reported to induce cell growth arrest, apoptosis and differentiation in tumor cells. The effect of the HDAC inhibitor, trichostatin A (TSA), on hepatoma cells, however, has not been well studied. In this study, we examined cell viability and gene expression profile in hepatoma cell lines treated with TSA. Methods: To study cell growth inhibition and induction of apoptosis by TSA on human hepatoma cell lines including HuH7, Hep3B, HepG2, and PLC/PRF/5, cells were treated with TSA at various concentrations and analyzed by the 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) and TUNEL assays, respectively. Changes in gene expression profile after exposure to TSA were assessed using a cDNA microarray consisting of 557 distinct cDNA of cancer-related genes. The levels of acetylated histones were examined by the chromatin immunoprecipitation (ChIP) assay using anti-acetylated histone H3 or H4 antibody. Results: The MTT assay demonstrated that TSA showed cell growth inhibition not only in a concentration-dependent but also a time-dependent manner on all cell lines studied. The TUNEL assay also revealed the potential of TSA to induce apoptosis. The microarray analysis revealed that 8 genes including collagen type 1, α2 (COL1A2), insulin-like growth factor binding protein 2 (IGFBP2), integrin, α7 (ITGA7), basigin (BSG), quiescin Q6 (QSCN6), superoxide dismutase 3, extracellular (SOD3), nerve growth factor receptor (NGFR), and p53-induced protein (PIG11) exhibited substantial induction (ratio >2.0) after TSA treatment in multiple cell lines. ChIP assay, in general, showed a good correlation between the expression level of mRNA and levels of acetylated histones in these upregulated genes. Conclusions: This study showed cell growth inhibition and the gene expression profile in hepatoma cell lines exposed to TSA. The alteration in levels of acetylated histones was closely associated with expression of specific cancer-related genes in hepatoma cells.
Unilateral Nevoid Telangiectasia Syndrome
Authors: Kreft B. , Marsch W.C. , Wohlrab J.
Published: September 2004

We report on a 29-year-old patient with a unilateral nevoid telangiectasia syndrome (UNTS). Based on microcirculation examinations, both functional impairments at the blood vessel level (laser-Doppler flowmetry) and morphologically altered capillaries (capillary microscopy) could be observed. We could demonstrate that microcirculatory examinations are suitable to demonstrate pathophysiological defects at the vascular level, especially since subclinical functional defects can also be recorded. To our knowledge, no such observations have yet been published with regards to UNTS.
Integrated Sun Protection Factor: A New Sun Protection Factor Based on Free Radicals Generated by UV Irradiation
Authors: Zastrow L. , Ferrero L. , Herrling T. , Groth N.
Published: September 2004

The present work uses the initial step of the whole cascade of biological effects in the skin, the creation of free radicals by means of UVA/UVB radiation, to develop a total sun protection factor. Until now, existing in vivo indices have not been fully satisfying: SPF only reflects protection from UVB light, and persistent pigment darkening is restricted to the UVA part of the sun spectrum. The quantitative measurement of free radicals generated in human skin biopsies by means of electron spin resonance X-band spectroscopy allows to determine a new total SPF. This new sun protection index covers all UVA/UVB wavelengths taking into account their effects in the epidermis as well as the dermis. Use of skin biopsies avoids exposure of human volunteers to potentially harmful radiations. The new index is always practically equal or lower than the in vivo SPF depending on the level of a product’s UVA/UVB photoprotection balance. With this, we propose to name this new protection index ‘integrated sun protection factor’.
Ectoin: An Effective Natural Substance to Prevent UVA-Induced Premature Photoaging
Authors: Buenger J. , Driller H.
Published: September 2004

With the help of a new ‘UVA stress model’, it was shown that Ectoin protects the skin from the effects of UVA-induced cell damage in a number of different ways. Using cell cultures, high-performance thin-layer chromatography, gel electrophoresis mobility shift assays, reverse transcriptase polymerase chain reaction, ion exchange chromatography and UV spectroscopy, it was demonstrated that the UVA-induced second messenger release, transcription factor AP-2 activation, intercellular adhesion molecule-1 expression and mitochondrial DNA mutation could be prevented. The results obtained clearly demonstrate that Ectoin counteracts the effects of UVA-induced and accelerated skin aging at different cell levels.
GERD: The Potential for Endoscopic Intervention
Authors: Triadafilopoulos George
Published: September 2004

Gastroesophageal reflux disease (GERD) is a common disorder that significantly affects patients’ quality of life. Most patients with symptomatic GERD do not have erosive reflux disease. Frequent transient lower oesophageal sphincter relaxations and the presence of hiatal hernia have emerged as major and interacting factors in GERD. Several endoscopic anti-reflux therapies aiming at creating an anti-reflux barrier and reducing or eliminating the need for chronic medical therapy or fundoplication have been introduced and validated as feasible, safe and effective. Today, it is possible to manage GERD patients with a multioption approach of medical, endoscopic or surgical therapies according to the size of hiatal hernia, the lower esophageal pressure profile and their clinical response to single-modality therapy.
Estrogen Reduces Serotonin-1A Receptor-Mediated Oxytocin Release and Gαi/o/z Proteins in the Hypothalamus of Ovariectomized Rats
Authors: D’Souza Deborah N. , Zhang Yahong , Damjanoska Katerina J. , Carrasco Gonzalo A. , Sullivan Nicole R. , Garcia Francisca , Battaglia George , DonCarlos Lydia L. , Muma Nancy A. , van de Kar Louis D.
Published: September 2004

The present study examined the effect of estradiol on hypothalamic serotonin-1A (5-HT1A) receptor signaling in female rats. We first examined the time-course effects of a single injection of the 5-HT1A receptor agonist (±)8-OH-DPAT (5, 15 or 30 min prior to decapitation), and dose response of (+)8-OH-DPAT (50, 100, 200 or 500 µg/kg, s.c.) on plasma hormones in ovariectomized rats that received a daily injection of β-estradiol 3-benzoate (10 µg/day, s.c.) or vehicle (sesame oil) for 2 days. In vehicle- and estrogen-treated rats, the peak response of hormones occurred at 15 min after injection and the time-course of oxytocin and adrenocorticotropic hormone (ACTH) responses to an injection of 8-OH-DPAT were comparable. However, only the oxytocin response was reduced by estrogen treatment. A second experiment compared the ACTH and oxytocin responses with doses of 50 or 200 µg/kg, s.c. of (+)8-OH-DPAT vs. (±)8-OH-DPAT in ovariectomized rats that were treated with oil or β-estradiol 3-benzoate (10 µg/day, s.c.) for 2 days. (+)8-OH-DPAT and (±)8-OH-DPAT produced a similar magnitude of increase in plasma levels of ACTH and oxytocin. Treatment with β-estradiol 3-benzoate produced a significant and comparable reduction in the oxytocin response to the highest dose (200 µg/kg, s.c.) of both (+)8-OH-DPAT and (±)8-OH-DPAT but did not alter the ACTH response to either (+)8-OH-DPAT or (±)8-OH-DPAT. In the dose-response experiment, a dose of 50 µg/kg of (+)8-OH-DPAT produced a maximal increase in plasma levels of ACTH, while the maximal oxytocin response was achieved with a dose of 200 µg/kg, s.c. Treatment with β-estradiol 3-benzoate reduced the maximal oxytocin response to (+)8-OH-DPAT (by 29%) but did not alter the ACTH response to any doses of (+)8-OH-DPAT. To examine potential mechanisms mediating the effects of estrogen on 5-HT1A receptor signaling, we measured the levels of Gαi, Gαo and Gαz proteins, which couple 5-HT1A receptors to their effector enzymes, in two subregions of the hypothalamus. The levels of Gαz protein were reduced in the mediobasal hypothalamus (containing the ventromedial and arcuate nuclei), which mainly expresses estrogen receptor-α, but not in the paraventricular hypothalamus, which mainly expresses estrogen receptor-β. Estradiol reduced the levels of Gαi2 and Gαi3 proteins in both hypothalamic regions but did not affect Gαi1 levels in either area. Combined, the data suggest that racemic and stereoselective 8-OH-DPAT have similar neuroendocrine effects and that both estrogen receptor-α and estrogen receptor-β mediate the reduction in levels of Gαi2,3 proteins.
Neuropeptide Y Is Released from Human Mammary and Radial Vascular Biopsies and Is a Functional Modulator of Sympathetic Cotransmission
Authors: Donoso M.V. , Miranda R. , Irarrázaval M.J. , Huidobro-Toro J. Pablo
Published: September 2004

The role of neuropeptide Y (NPY) as a modulator of the vasomotor responses mediated by sympathetic cotransmitters was examined by electrically evoking its release from the perivascular nerve terminals of second- to third-order human blood vessel biopsies and by studying the peptide-induced potentiation of the vasomotor responses evoked by exogenous adenosine 5′ triphosphate (ATP) and noradrenaline (NA). Electrical depolarization of nerve terminals in mammary vessels and radial artery biopsies elicited a rise in superfusate immunoreactive NPY (ir-NPY), which was chromatographically identical to a standard of human NPY (hNPY); a second peak was identified as oxidized hNPY. The amount released corresponds to 4–6% of the total NPY content in these vessels. Tissue extracts also revealed two peaks; hNPY accounted for 68–85% of the ir-NPY, while oxidized hNPY corresponded to 7–15%. The release process depended on extracellular calcium and on the frequency and duration of the electrical stimuli; guanethidine blocked the release, confirming the peptide’s sympathetic origin. Assessment of the functional activity of the oxidized product demonstrated that while it did not change basal tension, the NA-evoked contractions were potentiated to the same extent as with native hNPY. Moreover, NPY potentiated both the vasomotor action of ATP or NA alone and the vasoconstriction elicited by the simultaneous application of both cotransmitters. RT-PCR detected the mRNA coding for the NPY Y1 receptor. In summary, the release of hNPY or its oxidized species, elicited by nerve terminal depolarization, coupled to the potentiation of the sympathetic cotransmitter vasomotor responses, highlights the modulator role of NPY in both arteries and veins, strongly suggesting its involvement in human vascular sympathetic reflexes.
Intestinal Metaplasia of Gastric Cardia and Carditis in Japanese Patients with Helicobacter pylori Infection
Authors: Yagi Kazuyoshi , Nakamura Atsuo , Sekine Atsuo
Published: September 2004

Aim: The purpose of this study was to determine the prevalence of intestinal metaplasia of the gastric cardia in Japanese patients with Helicobacter pylori infection. Methods: One hundred and fifty-seven patients with H. pylori infection participated in this study. Four biopsy specimens were taken from antrum, lesser and greater curvatures of stomach, and cardia for histological examination. The patients were divided into three groups: those ≤39 years of age (group A), those 40–59 years old (group B), and those ≧60 years of age (group C). Results: The proportions of the patients with intestinal metaplasia of the gastric cardia in the three groups were 12, 39, and 65%, respectively. Their intestinal metaplasia of gastric cardia scores were 0.2, 0.54, and 0.81, respectively (significant difference among groups A, B, and C: p < 0.05), according to the updated Sydney classification. Conclusion: The prevalence of intestinal metaplasia of the gastric cardia and carditis in Japanese patients with H. pylori infection was similar to that of metaplasia of antrum and lesser curvature of the stomach.
Depressive Symptoms Increase the Likelihood of Cognitive Impairment in Elderly People with Subclinical Alzheimer Pathology
Authors: Milwain Elizabeth J. , Nagy Zsuzsanna
Published: September 2004

The objective of this study was to investigate whether the presence of depressive symptoms influences the clinical expression of Alzheimer’s pathology. We have analysed the relationships between the severity of Alzheimer’s pathology and cognitive decline in two patient groups defined by the presence or absence of depressive symptoms. The study included 89 subjects who participated in a longitudinal research programme prior to death, underwent post-mortem examination and were found to have only Alzheimer-type pathology in their brains, ranging in severity from the entorhinal to neocortical stages. Our results indicate that depressive symptoms did not influence cognition in the early (entorhinal) stages of Alzheimer’s disease (AD; where cognition was good regardless of whether or not there was evidence for depressive symptoms) or in the late (neocortical) stages (where cognition was poor regardless of whether or not there was evidence for depression). However, in the intermediate (limbic) stages, patients with depressive symptoms had significantly worse cognitive performance (mean CAMCOG of 32) than those who did not (mean CAMCOG of 73). We conclude that depressive symptoms may contribute to the cognitive decline of AD patients in that pathology, that would be otherwise silent, becomes clinically apparent. Therefore, a multiple diagnosis of early AD and depression should be more widely considered in elderly persons presenting with mild cognitive decline and depression. Treating the depressive symptoms would benefit the patient, but the cognitive improvement may not indicate that AD is absent.
Do the Recently Modified Pacemaker Guidelines for Neurocardiogenic Syncope Also Apply to Young Patients?
Authors: Wagshal Alan B. , Weinstein Jean Marc , Weinstein Orly , Zeldetz Vladimir , Damri Esther , Ilia Reuven , Katz Amos
Published: September 2004

To assess the classification of neurocardiogenic syncope (NCS) as a IIA indication for pacemaker implantation in the recent American College of Cardiology/American Heart Association Task Force on Practice Guidelines/North American Society for Pacing and Electrophysiology guidelines, we performed chart reviews and follow-up interviews in a cohort of 45 consecutive young Israeli soldiers (age 18–24 years) with a history of syncope (mean of 9 prior syncopal episodes) and a positive tilt test treated with drug therapy. Asystole longer than 5 s during tilt testing occurred in 11 patients. Five years later, we found that only 2 patients were still taking medications, only 1 patient (2%) still reported frequent syncopal or near-syncopal episodes and 3 patients (7%) had rare symptoms (no more than one syncopal episode during the past 2 years), while the remaining 40 (89%) were symptom free off medications. Thus, NCS in young patients, even with prolonged asystole during tilt testing, a history of frequent syncopal episodes and other high- risk factors described in the guidelines, is often a self-limiting disorder, perhaps stress related or situational in nature; an overwhelming number of patients become asymptomatic and stop taking medications within 1–2 years. These patients do not require long-term therapy; thus, our data would suggest that the IIA pacing indication for NCS should be restricted to older patients.
Neuropsychological Correlates of the PANSS Cognitive Factor
Authors: Ehmann T.S. , Khanbhai I. , MacEwan G.W. , Smith G.N. , Honer W.G. , Flynn S. , Altman S.
Published: September 2004

Objective: Factor analytic studies of the Positive and Negative Syndrome Scale (PANSS) have consistently isolated a factor that is frequently labeled as ‘cognitive’. The present study sought to further explore the factor by examining the relationships between 4 versions of the cognitive factor and a set of neuropsychological tests. Method: Thirty-seven inpatients diagnosed with schizophrenia or schizoaffective disorder were assessed with the PANSS and neuropsychological measures. Results: Verbal intelligence and verbal memory were found to be most closely associated with cognitive factor scores. A global rating of illness severity showed greater relationships to cognitive variables than any cognitive factor. Conclusions: The PANSS cognitive factor may reflect verbal ability and memory, but is not sufficiently comprehensive to be considered as a replacement for direct assessment of cognitive functioning.
Activity of Levofloxacin and Ciprofloxacin in Combination with Cefepime, Ceftazidime, Imipenem, Piperacillin-Tazobactam and Amikacin against Different Pseudomonas aeruginosa Phenotypes and Acinetobacter spp.
Authors: Drago Lorenzo , De Vecchi Elena , Nicola Lucia , Colombo Alberto , Guerra Anna , Gismondo Maria Rita
Published: September 2004

Background: Combination therapy is used to widen the antimicrobial spectrum, minimize toxicity and prevent the emergence of resistant mutants. Methods: Synergy between levofloxacin or ciprofloxacin and ceftazidime, cefepime, imipenem, piperacillin-tazobactam and amikacin was evaluated by checkerboard assay with 55 strains and by time-kill curves with 8 strains of Pseudomonasaeruginosa and Acinetobacter spp. Results: In the checkerboard assay, synergy and additivity were the most frequent effects observed among all the combinations against P. aeruginosa and Acinetobacter spp., with no significant differences between the two fluoroquinolones. No antagonism was observed. In the time-kill curves, synergy was evidenced against all the tested strains, at least for one combination at one of the time points considered. Levofloxacin and ciprofloxacin combined with ceftazidime, as well as levofloxacin plus amikacin, were synergistic for all the strains tested. Conclusion: Combinations of fluoroquinolones with β-lactams or amikacin show an enhanced activity against P. aeruginosa and Acinetobacter spp.
Association between Physical and Cognitive Function in Healthy Elderly: The Health, Aging and Body Composition Study
Authors: Rosano Caterina , Simonsick Eleanor M. , Harris Tamara B. , Kritchevsky Steven B. , Brach Jennifer , Visser Marjolein , Yaffe Kristine , Newman Anne B.
Published: September 2004

Performance measures of physical function (gait speed, chair stands, standing balance) and cognitive function [Teng-modified Mini-Mental Status Exam (3MS) and digit symbol substitution test (DSST)] were assessed at baseline in 3,075 participants in the Health, Aging and Body Composition Study. Each physical function measure was examined for the strength and magnitude of association with cognitive function. All physical function measures were associated with both the 3MS and DSST scores (p < 0.001), and in multivariate analysis each relationship was independent of demographic characteristics, weight, physical activity and comorbid health conditions of participants. The association of motor performance was consistently greater for the DSST than the 3MS and, among the motor tests, gait speed retained a significant association with both cognitive measures independent of demographic, weight, physical activity and comorbid health conditions. In this large cohort of high-functioning older adults, the correlation between physical and cognitive function was not entirely explained by demographics. Longitudinal studies are needed to determine the direction of causality in this relationship.