bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulated Secretion of Pro‐Opiomelanocortin Converting Enzyme and an Aminopeptidase B‐Like Enzyme from Dispersed Bovine Intermediate Lobe Pituitary Cells
Authors: Castro Maria G. , Birch Nigel P. , Loh Y. Peng
Published: October 2006

Abstract: Coordinate secretion of two prohormone/proneuropeptide processing enzymes [pro‐opiomelanocortin converting enzyme (PCE) and an aminopeptidase B‐like enzyme (APBE)] and α‐melanotropin (α‐MSH) from bovine intermediate lobe pituitary cells was studied. Stimulation of secretion with 8‐bromo‐cyclic AMP produced significant increases in levels of immunoreactive α‐MSH, PCE, and APBE. Treatment of cells with the dopaminergic agonist 2‐bromo‐α‐ergocryptine resulted in significant decreases in secretion of α‐MSH, PCE, and APBE. In neither case were there significant changes in levels of cytosolic lactic dehydrogenase or lysosomal β‐glucuronidase in the medium. The secreted PCE activity was shown to process frog and mouse pro‐opiomelanocortin primarily to 23,000‐Mr corticotropin (ACTH), 13,000‐Mr ACTH, β‐lipotropin, a β‐endorphin‐like peptide, and β‐endorphin, products comparable to those synthesized by the mouse and frog intermediate lobe in situ. The secreted enzymatic activity had a pH optimum between 4.0 and 5.0, was strongly inhibited by pepstatin A, and had an inhibitor profile similar to the purified bovine intermediate lobe PCE. The secreted APBE activity cleaved Arg0‐[Met]‐enkephalin to [Met]‐enkephalin and had a pH optimum and inhibitor profile similar to that previously reported for an activity from purified secretory vesicle fractions of bovine intermediate and neural lobes. The coordinate regulated secretion of α‐MSH and enzyme activities (PCE and APBE) strongly indicates their colocalization in the same secretory vesicle compartment within the cell. The characteristics of the two enzymes secreted in the medium paralleled those seen in the tissue and further support their role in pro‐opiomelanocortin processing in vivo.
Adrenergic Receptors in Aging and Alzheimer's Disease: Increased β2‐Receptors in Prefrontal Cortex and Hippocampus
Authors: Kalaria R. N. , Andorn A. C. , Tabaton M. , Whitehouse P. J. , Harik S. I. , Unnerstall J. R.
Published: October 2006

Abstract: Loss of pigmented noradrenergic locus ceruleus neurons occurs in Alzheimer's disease (AD) and, to a lesser extent, in aging. We studied β‐adrenergic receptors and their subtypes, β1 and β2, by the specific binding of 125I‐pindolol to particulate membrane preparations from prefrontal cortex, hippocampus, putamen, and cerebellum and to sections from frontal cortex by in vitro autoradiography. In prefrontal cortex from controls, numbers of total β‐ and β‐adrenoceptors did not significantly correlate with age, but number of β1‐adrenoceptors showed a weak but significant negative correlation. Binding in tissue particulate preparations to total β‐receptors did not reveal significant differences in samples from prefrontal cortex between AD subjects and age‐matched controls. However, β1‐adrenoceptors were decreased and β2‐adrenoceptors were increased in number by ∼30‐50% in AD subjects. Thus, the relative ratio of β/β2‐receptors was decreased in AD. Binding by in vitro receptor autoradiography performed in a subset of samples of frontal cortex also showed β2‐adrenoceptors, and less consistently total β‐and β1recep‐tors, to be increased significantly in number in cortical laminae II, III, IV, and V of tissue sections from AD subjects. In these subjects, number of locus ceruleus cells and norepinephrine concentrations in putamen and frontal cortex were markedly reduced compared with values in controls. In the hippocampus, total β‐ and both β2‐ and β1‐adrenoceptors were increased in number in AD. In contrast, in the putamen. where β‐receptors predominate, total β‐ and β1‐receptors were significantly decreased in number with no consistent change in content of β2‐receptors in AD. There were no significant changes in the cerebellum. Specific pindolol binding was not affected by interval between death and sampling of tissue at autopsy. Our results indicate selective changes in number of β‐receptors in AD. These changes in the cortex and hippocampus suggest receptor upregulation in response to noradrenergic deafferentation from the locus ceruleus or may simply reflect glial proliferation in AD.
Accumulation of Cyclic AMP Elicited by Vasoactive Intestinal Peptide Is Potentiated by Noradrenaline, Histamine, Adenosine, Baclofen, Phorbol Esters, and Ouabain in Mouse Cerebral Cortical Slices: Studies on the Role of Arachidonic Acid Metabolites and Protein Kinase C
Authors: Schaad Nicolas C. , Schorderet Michel , Magistretti Pierre J.
Published: October 2006

Abstract: In mouse cerebral cortical slices, noradrenaline (NA) potentiates cyclic AMP (cAMP) accumulation elicited by vasoactive intestinal peptide (VIP) through α1‐adrenergic receptors. This synergism is inhibited by indomethacin, and the prostaglandins E2 and F2α mimic the effect of NA. In the present study, we observed that the synergism between VIP and NA is not inhibited by the protein kinase C inhibitor 1‐(5‐isoquinolinylsulfonyI)‐2‐methylpiperazine (H‐7) or the diacylglycerol‐lipase inhibitor RHC 80267, thus further stressing the role of phospholipase A2 activation. Various neuroactive agents that potentiate the stimulatory effect of VIP on cAMP formation were also examined. As with NA, the potentiation by histamine and adenosine is inhibited by indomethacin. In contrast to NA, histamine, and adenosine, the synergistic interaction between phorbol esters and VIP on cAMP formation is abolished by H‐7 but not by indomethacin. The potentiation by baclofen, a y‐aminobutyric acidB receptor agonist, is partially inhibited by the 5‐lipox‐ygenase inhibitor nafazatrom. The synergism between ouabain and VIP is reduced by H‐7 but not by indomethacin and nafazatrom. These data indicate that the stimulation of cAMP formation elicited by VIP is under the modulation of various neuroactive agents that trigger diverse intracellular mechanisms to potentiate the effect of the peptide.
Blood–Brain Barrier Permeability to Sodium. Modification by Glucose or Insulin?
Authors: Knudsen Gitte Moos , Jakobsen Johannes
Published: October 2006

Abstract: In order to explore the pathogenetic mechanism underlying the changes in blood‐brain barrier sodium transport in experimental diabetes, the effects of hyperglycemia and of hypoinsulinemia were studied in nondiabetic rats. In untreated diabetes, the neocortical blood‐brain barrier permeability for sodium decreased by 20% (5.6 ± 0.7 versus 7.0 ± 0.8 × 105 ml/g/s) as compared to controls. Intravenous infusion of 50% glucose for 2 h was associated with a decrease in the blood‐brain barrier permeability to sodium (5.4 ± 1.2 × 105 ml/g/s), whereas rats treated with an inhibitor of insulinsecretion (SMS 201–995, a somatostatin‐analogue) had normal sodium permeability (7.3 ± 2.0 × 105 ml/g/s). Acute insulin treatment of diabetic rats normalized the sodium permeability within a few hours as compared to a separate control group (7.7 ± 1.1 versus 6.9 ± 1.4 × 105 ml/g/s). To elucidate whether the abnormal blood‐brain barrier passage is caused by a metabolic effect of glucose or by the concomitant hyperosmolality, rats were made hyperosmolar by intravenous injection of 50% mannitol. Although not statistically significant, blood‐brain barrier sodium permeability increased in hyperosmolar rats as compared to the control rats (8.3 ± 1.0 and 7.0 ± 1.9 × 105 ml/g/s, respectively). It is concluded that either hyperglycemia per se or a glucose metabolite is responsible for the blood‐brain barrier abnormality which occurs in diabetes. Further, we suggest that the specific decrease of sodium permeability could be the result of glucose‐mediated inhibition of the Na+K+‐ATPase localized at the blood‐brain barrier.
Regulation by Dibutyryl Cyclic AMP of Carnosine Synthesis in Astroglia‐Rich Primary Cultures Kept in Serum‐Free Medium
Authors: Schulz Michael , Hamprecht Bernd , Kleinkauf Horst , Bauer Karl
Published: October 2006

Abstract: The synthesis of carnosine (β‐Ala‐His) by astroglia‐rich primary cultures was much higher if the cells were cultivated in Ham's nutrient mixture F‐12 than if they were grown in Dulbecco's modified Eagle's medium. Carnosine synthesis was not affected by the presence of insulin, trans‐ferrin. phorbol myristate acetate, or dexamethasone. However. dibutyryl cyclic AMP and other agents that can, directly or ndirectly, activate cyclic AMP‐dependent protein kinases strongly lower the rate of carnosine synthesis. The depression of carnosine synthesis was dependent on the concentration of dibutyryl cyclic AMP. The effect was maximal (approximately 80% inhibition) in cultures preincubated with 1 mM dibutyryl cyclic AMP for 4 days. The adenylate cyclase activator forskolin, the phosphodiesterase inhibitor 3‐isobutyl‐1‐methylxanthine, and 8‐bromo‐cyclic AMP caused the same depression as dibutyryl cyclic AMP, whereas neither butyrate nor dibutyryl cyclic GMP elicited any effect.
Mitogenic Effect of Axolemma‐Enriched Fraction on Cultured Oligodendrocytes
Authors: Chen Shu‐Jen , De Vries George H.
Published: October 2006

Abstract: An in vitro system has been devised to study the mitogenic effect of axolemma on cultured oligodendrocytes. Addition of axolemma‐enriched fraction to cultured oligodendrocytes results in a dose‐dependent mitotic response with an 11‐fold stimulation at a membrane concentration of 200 μg/ml. The interaction between oligodendrocytes and axolemma is specific, as myelin‐enriched fraction, astrocyte membrane, and red blood cell membrane showed little or no effect on the oligodendroglial proliferation under similar conditions. In addition, cultured astrocytes were tested with the same axolemma membrane, and no mitotic stimulation was observed. The mitogenicity of AEF membrane on cultured oligodendrocytes is sensitive to heat and trypsin treatment, suggesting that the axolemma mitogen may be a protein.
Octopamine Uptake and Metabolism in the Insect Nervous System
Authors: Wierenga Joel M. , Hollingworth Robert M.
Published: October 2006

Several insect tissues were examined for their ability to take up octopamine in the presence and absence of sodium ions. The cockroach Malpighian tubules, ovary, and ventral nerve cord showed the highest level of sodium‐dependent uptake. The adult firefly lantern exhibited substantial sodiumindependent uptake. Some of these tissues were also examined for their ability to metabolize octopamine by N‐acetylation. Measurable N‐acetyltransferase activity was present in the cockroach ventral nerve cord, tobacco hornworm CNS, and firefly light organ. N‐Acetylation is proposed to be the major metabolic pathway for octopamine in the cockroach (Periplaneta americana) nervous system. Several classes of compounds, including octopamine receptor agonists, tricyclic antidepressants, amphetamines, chloroethylbenzylamines, and some experimental insecticides, were tested for their ability to inhibit octopamine uptake and metabolism. The sodium‐insensitive component of uptake was not inhibited by most compounds tested, but the sodium‐sensitive component was strongly inhibited by xylamine, N‐ethyl‐N‐chloroethyl‐o‐bromobenzylamine, and their aziridinium ions (60–100%). These compounds also effectively inhibited N‐acetyltransferase (IC50 values at or below 1 μM). Other good inhibitors of N‐acetyltransferase included desipramine, synephrine, and an experimental insecticide, CGA 132427. Formamidine pesticides had limited effect on both processes, and neither action seems likely to be involved in their octopaminergic actions in vivo. Cocaine was unique in stimulating N‐acetyltransferase activity. When inhibition of sodium‐sensitive uptake is compared with inhibition of N‐acetyltransferase in the cockroach ventral nerve cord, two groups of inhibitors are discernible. Type 1 compounds inhibit uptake without an effect on N‐acetyltransferase, whereas type 2 compounds inhibit both processes. These results suggest a functional linkage between the uptake and acetylation of octopamine.
Acid Lability of Metabolites of 2‐Deoxyglucose in Rat Brain: Implications for Estimates of Kinetic Parameters of Deoxyglucose Phosphorylation and Transport Between Blood and Brain
Authors: Dienel Gerald A. , Cruz Nancy F. , Mori Kentaro , Sokoloff Louis
Published: October 2006

The steady‐state brain/plasma distribution ratios of [14C]deoxyglucose ([14C]DG) for hypoglycemic rats previously determined by measurement of DG concentrations in neutralized acid extracts of freeze‐blown brain and plasma exceeded those predicted by simulations of kinetics of the DG model. Overestimation of the true size of the precursor pool of [14C]DG for transport and phosphorylation could arise from sequestration of [14C]DG within brain compartments and/or instability of metabolites of [14C] DG and regeneration of free [14C]DG during the experimental period or extraction procedure. In the present study, the concentrations of [14C]DG and glucose were compared in samples of rat brain and plasma extracted in parallel with perchloric acid or 65% ethanol containing phosphate‐buffered saline. The concentrations of both hexoses in acid extracts of brain were higher than those in ethanol, whereas hexose contents of plasma were not dependent on the extraction procedure. The magnitude of overestimation of DG content (about 1.2 to fourfold) varied with glucose level and was highest in extracts isolated from hypoglycemic rats; contamination of the [14C]DG fraction with 14C‐labeled nonacidic metabolites also contributed to this overestimation. Glucose concentrations in acid extracts of brain exceeded those of the ethanol extracts by < 40% for normal and hypoglycemic rats.
Prevention of hepatic fibrosis in nonobese diabetic mice: a critical role for interferon‐γ
Authors: Mukai Tsuyoshi , Nagaki Masahito , Imose Motoaki , Kimura Kiminori , Satake Shinichi , Takai Shinji , Moriwaki Hisataka
Published: September 2006

Abstract: Background/Aims: Nonobese diabetic (NOD) mice, a model of type I diabetes mellitus, harbor certain unique defects in their immune system. The aim of this study was to investigate how NOD mice show hepatic injury and subsequent fibrogenic responses.

Methods: Hepatic fibrosis was induced by intraperitoneal injections of dimethylnitrosamine (DMN), and assessed biochemically and histologically. Expressions of cytokine messenger RNA (mRNA) in the liver were determined.

Results: In a model of liver cirrhosis induced by dimethylnitrosamine (DMN), we found that NOD mice had lower levels of hepatic fibrosis and better survival than control ICR mice. The resistance to DMN‐induced lethality in NOD mice was independent of apoptosis and necrosis of hepatocytes, but apparently due to the prevention of hepatic fibrosis. We also found increased inductions of interferon‐γ (IFN‐γ) mRNA in the liver of NOD mice and of intracellular IFN‐γ from intrahepatic T cells following DMN administration. Treatment with neutralizing anti‐IFN‐γ‐antibody cancelled the inhibition of hepatic fibrosis in NOD mice.

Conclusions: These results suggest that IFN‐γ is effective for inhibiting hepatic fibrosis and that genetic host factors may be important in determining differential responses to injury.
Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta‐analysis of prospective randomized‐controlled trials
Authors: Khurana Sandeep , Singh Pankaj
Published: September 2006

Abstract: Objectives: To determine the safety and efficacy of rifampin for treatment of pruritus associated with cholestasis due to chronic liver disease.

Methods: Medical literature was searched systematically using keywords as rifampicin, rifampin, rifamycin, cholestasis, pruritus, itching, and liver disease. Trials that compared the efficacy of rifampin with placebo/alternative for treatment of pruritus due to chronic cholestasis were selected for analysis. Primary outcomes were resolution of pruritus and development of side effects. Association was measured with the odds ratio (OR). Breslow–Day method was used to treat for homogeneity under null hypothesis that OR was consistent across all the trials. Corrected Mantel–Haenszel χ2 test was used to test if OR differed systematically from value of 1.

Results: Five prospective randomized‐controlled cross‐over trials with 61 patients were identified. Treatment with rifampin led to complete or partial resolution of pruritus in 47 (77%) patients as compared with 12(20%) treated with placebo or alternative (OR 15.2, 95% confidence interval 5.2–45.6, P=0.001). Four (7%) patients treated with rifampin suffered side effects, which resolved after its discontinuation. There was no incidence of hepatotoxicity. Test of heterogeneity for primary end points among the trials was not significant (P=0.16).

Conclusion: This meta‐analysis suggests that rifampin is safe and effective for treatment of pruritus due to chronic cholestasis. This analysis also suggests that use of rifampin for short duration is associated with a low risk of hepatotoxicity.
A Community‐Based Study of Helicobacter pylori Therapy Using the Strategy of Test, Treat, Retest, and Re‐treat Initial Treatment Failures
Authors: Lee Yi‐Chia , Wu Hui‐Min , Chen Tony Hsiu‐Hsi , Liu Tzeng‐Ying , Chiu Han‐Mo , Chang Chun‐Chao , Wang Hsiu‐Po , Wu Ming‐Shiang , Chiang Hung , Wu Meng‐Chen , Lin Jaw‐Town
Published: September 2006

Background:  Although eradication of Helicobacter pylori infection can decrease the risk of gastric cancer, the optimal regimen for treating the general population remains unclear. We report the eradication rate (intention‐to‐treat and per protocol) of a community‐based H. pylori therapy using the strategy of test, treat, retest, and re‐treat initial treatment failures.

Materials and methods:  In 2004, a total of 2658 residents were recruited for 13C‐urea breath testing. Participants with positive results for infection received a standard 7‐day triple therapy (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily), and a 10‐day re‐treatment (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once daily) if the follow‐up tests remained positive. Both H. pylori status and side‐effects were assessed 6 weeks after treatment.

Results:  Among 886 valid reporters, eradication rates with initial therapy were 86.9% (95% confidence interval [CI]: 84.7–89.1%) and 88.7% (95%CI: 86.5–90.9%) by intention‐to‐treat and per protocol analysis, respectively. Re‐treatment eradicated infection in 91.4% (95%CI: 86–96.8%) of 105 nonresponders. Adequate compliance was achieved in 798 (90.1%) of 886 subjects receiving the initial treatment and in all 105 re‐treated subjects. Mild side‐effects occurred in 24% of subjects. Overall intention‐to‐treat and per protocol eradication rates were 97.7% (95%CI: 96.7–98.7%) and 98.8% (95%CI: 98.5–99.3%), respectively, which were only affected by poor compliance (odds ratio, 3.3; 95%CI, 1.99–5.48; p < .0001).

Conclusions:  A comprehensive plan using drugs in which the resistance rate is low in a population combined with the strategy of test, treat, retest, and re‐treat of needed can result in virtual eradication of H. pylori from a population. This provides a model for planning country‐ or region‐wide eradication programs.
Polymorphisms in Cytokine Genes and Risk of Helicobacter pylori Infection among Jamaican Children
Authors: Tseng Fan‐Chen , Brown Elizabeth E. , Maiese Eric M. , Yeager Meredith , Welch Robert , Gold Benjamin D. , Owens Marilyn , Cranston Beverly , Hanchard Barrie , El‐Omar Emad , Hisada Michie
Published: September 2006

Background:  Infection by Helicobacter pylori is often acquired during childhood. Recent studies suggest that inflammatory cytokines may play a role in susceptibility to, and disease phenotype caused by, H. pylori infection, but the association of host genetic variability with risk of H. pylori infection has not been studied in children.

Methods:  We investigated the relationship between the risk of H. pylori antibody positivity and cytokine gene polymorphisms among 199 two‐year‐old Jamaicans. H. pylori seropositivity was determined by a validated research enzyme‐linked immunosorbent assay. Real‐time Taqman® polymerase chain reaction was used to determine variants at 17 loci in 11 cytokine genes (IL1A, IL1B, IL2, TNF, TLR4, IL4, IL6, IL10, IL10RA, IL12A and IL13). We estimated the odds ratio and the 95% confidence interval for the association of genetic polymorphisms with H. pylori seropositivity, using logistic regression.

Results:  Forty (20.1%) of 199 children were seropositive. Children's H. pylori seropositivity correlated highly with maternal H. pylori seropositivity (OR = 7.98, 95% CI = 1.05–60.60, p = .02). Children carrying IL1A−889T had a lower risk of H. pylori positivity, compared to those carrying −889C, with each T allele associated with 43% risk reduction (OR = 0.57, 95% CI = 0.33–0.99, p‐trend = .05). No other loci we examined were associated with the risk of H. pylori seropositivity.

Conclusions:  The IL1A−889 T allele, known to express a higher level of cytokine IL‐1α, is associated with a lower risk of H. pylori infection among Jamaican children. Our finding supports the hypothesis that an upregulation of pro‐inflammatory cytokines may protect against persistent H. pylori colonization.
Helicobacter pylori Recurrence in Patients with Duodenal Ulcer: Clinical, Endoscopic, Histologic, and Genotypic Aspects. A 10‐Year Brazilian Series
Authors: Eisig Jaime N. , Zaterka Schlioma , Silva Fernando M. , Malfertheiner Peter , Mattar Rejane , Rodriguez Tomás N. , Hashimoto Cláudio L. , Iriya Kioshi , Laudanna Antonio A. , Moraes‐Filho Joaquim P.P.
Published: September 2006

Background:  Recurrence infection following successful eradication of Helicobacter pylori is usually low, except for countries with high prevalence of H. pylori. The aim of this study was to verify H. pylori recurrence rate in patients with duodenal ulcer after eradication and the possible relationship with environmental factors, histologic pattern of the mucosa and bacterial genotype.

Materials and methods:  One‐hundred and ninety‐four patients with an active duodenal ulcer and who were successfully treated for H. pylori infection from 1990 to 1999 were studied. A questionnaire was answered about their living conditions, and a 14C‐urea breath test was performed. Patients with a positive breath test underwent an upper endoscopy to investigate for possible ulcer recurrence; gastric biopsy samples were than collected for rapid urease test and for histologic assessment. H. pylori vacA and cagA genotype was determined by polymerase chain reaction in those samples with positive urease test.

Results:  H. pylori infection was detected in 11 patients (recurrence rate of 5.7%) that were not associated with the type of bacterial virulence. In 10 patients the ulcer was healed and all of them were clinically asymptomatic. In eight, histology showed an intensification of gastritis. All 11 patients had adequate housing and sanitary conditions and no other risk for H. pylori recurrence was identified.

Conclusions:  The recurrence rate of H. pylori in Brazil was higher than that reported in developed countries, but lower than usually reported in developing ones. Ulcer relapse rarely occurs even in long‐term follow up.
Comparison of Amoxicillin–Metronidazole Plus Famotidine or Lansoprazole for Amoxicillin–Clarithromycin–Proton Pump Inhibitor Treatment Failures for Helicobacter pylori Infection
Authors: Murakami Kazunari , Okimoto Tadayoshi , Kodama Masaaki , Sato Ryugo , Miyajima Hajime , Ono Masami , Inoue Kunimitsu , Watanabe Koichiro , Otsu Satoshi , Fujioka Toshio
Published: September 2006

Background:  Proton pump inhibitor–amoxicillin–metronidazole is recommended as second‐line Helicobacter pylori therapy in Japan. The authors assessed the efficacy and safety of second‐line eradication using the H2‐receptor antagonist famotidine as a substitute for proton pump inhibitor.

Materials and methods:  Sixty‐one patients who failed in first‐line H. pylori eradication using proton pump inhibitor–clarithromycin–amoxicillin were randomly assigned to either second‐line therapy including metronidazole: a 7‐day course of lansoprazole 30 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (lansoprazole group); or a 7‐day course of famotidine 40 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (famotidine group). Eradication was assessed for each group at least 4 weeks after completing eradication therapy. Drug susceptibility test was performed using 57 strains in pretreatment to clarithromycin, metronidazole, and amoxicillin.

Results:  Prior to second‐line H. pylori eradication, the rate of resistance to clarithromycin was high at 84% (48/57). Similarly, resistance to metronidazole was low at 5.3% (3/57); however, no amoxicillin‐resistant strains were found.

The eradication rates for both lansoprazole and famotidine treatment groups were high at 97% (29/30) and 94% (29/31), respectively.

Conclusions:  Famotidine treatment including metronidazole–amoxicillin as second‐line therapy provided a high eradication rate similar to lansoprazole therapy. Famotidine is therefore expected to serve as a useful H. pylori eradication regimen in patients with proton pump inhibitor allergy, an economic benefit in terms of reduced health‐care costs is also anticipated.
Acute Symptomatic Gastritis Due to Helicobacter heilmannii
Authors: Al‐Hamoudi Waleed K. , Alpert Lesley , Szilagyi Andrew
Published: September 2006

Helicobacter heilmannii is a Gram‐negative spiral‐shaped organism predominantly associated with zoonotic infection. Human pathology has also been described, but acute symptoms with complete resolution have been infrequently reported. We present a 50‐year‐old man in whom H. heilmannii gastritis presented as an acute febrile illness and was successfully treated with antibiotics and proton pump inhibitor. Epidemiology, diagnosis, and treatment of similar cases are reviewed.
Helicobacter pylori Infection and CagA Protein Translocation in Human Primary Gastric Epithelial Cell Culture
Authors: Lai Yo‐Ping , Yang Jyh‐Chin , Lin Tzu‐Zung , Lin Jaw‐Town , Wang Jin‐Town
Published: September 2006

Background:  Increasing evidence has shown that Helicobacter pylori CagA protein translocation into gastric epithelial cells plays an important role in the development of gastric inflammation and malignancy. Translocated CagA undergoes tyrosine phosphorylation in gastric adenocarcinoma cell line cells, and CagA involves disruption of cellular apical–junction complex in Madin–Darby canine kidney cells.

Methods:  To elucidate whether these events take place in normal human gastric epithelium, we infected human primary gastric epithelial cells with H. pylori.

Results:  Our results demonstrate that CagA protein was translocated into primary gastric epithelial cells and tyrosine phosphorylated. The translocated CagA induces cytoskeletal rearrangement and the disruption of tight junctions in primary gastric epithelial cells.

Conclusions:  This study provides direct evidence of the modulation of gastric epithelial cells by CagA protein translocation, and advances our understanding of the pathogenesis of H. pylori infection.
Apoptosis in Helicobacter pylori Gastritis is Related to cagA Status
Authors: Cabral Mônica M.D.A. , Mendes Cláudia M.C. , Castro Lúcia P.F. , Cartelle Christiane T. , Guerra Juliana , Queiroz Dulciene M.M. , Nogueira Ana M.M.F.
Published: September 2006

Background:  Helicobacter pylori infection increases gastric epithelial cell apoptosis; however, the influence of cagA status is still controversial. We aimed to investigate if cagA status is related to apoptosis in H. pylori gastritis at different anatomic sites of the gastric mucosa.

Materials and Methods:  We studied by immunohistochemistry (streptavidin–biotin method) pro‐apoptotic (Bax and Bak) and antiapoptotic (Bcl‐2 and Bcl‐x) proteins expression, scored from 0 to 4, in gastric biopsies, at the antrum (lesser and greater curvatures), incisura, and corpus (greater curvature) from 50 patients with H. pylori gastritis (22 males, 28 females, median age 40 years) and eight non‐infected patients (6 males, median age 39.6 years). H. pylori and cagA status were determined by polymerase chain reaction.

Results:  Apoptotic proteins were expressed in a granular pattern, in the cytoplasm of foveolar cells; Bax and Bak expression was higher than Bcl‐2 and Bcl‐x in most cases and was significantly higher in patients infected by cagA‐positive strains than in those infected by cagA‐negative strains (p = .001). Bak expression was higher at the lesser curvature (antrum and incisura) than in the other regions (p = .002) and was correlated with atrophy. Anti‐apoptotic proteins were significantly more expressed at the antral lesser curvature than in the other regions of the stomach (Bcl‐2: p = .02; Bcl‐x: p < .001).

Conclusions:  Infection with cagA‐positive strains is significantly associated with overexpression of pro‐apoptotic proteins in the gastric mucosa, mainly at the antral lesser curvature, which may have a role on atrophy development. Anti‐apoptotic proteins were also overexpressed at the lesser curvature, which may occur to keep epithelial cell turnover or might be related to malignant transformation.
In Vitro and In Vivo Complementation of the Helicobacter pylori Arginase Mutant Using an Intergenic Chromosomal Site
Authors: Langford Melanie L. , Zabaleta Jovanny , Ochoa Augusto C. , Testerman Traci L. , McGee David J.
Published: September 2006

Background:  Gene complementation strategies are important in validating the roles of genes in specific phenotypes. Complementation systems in Helicobacter pylori include shuttle vectors, which transform H. pylori at relatively low frequencies, and chromosomally based approaches. Chromosomal complementation strategies are susceptible to polar effects and disruption of other H. pylori genes, leading to unwanted pleiotropic effects.

Materials and methods:  A new complementation strategy was developed for H. pylori by utilizing a suicide plasmid vector that contains fragments of an H. pylori intergenic region (hp0203–hp0204), a chloramphenicol acetyltransferase cassette (cat), and a multiple‐cloning site. Genes of interest could be cloned into the intergenic plasmid and the genes integrated into H. pylori by homologous recombination into the intergenic chromosomal region without disrupting any annotated H. pylori gene. The complementation system was validated using the gene encoding arginase (rocF).

Results:  A rocF mutant unable to hydrolyze or consume l‐arginine regained these functions by complementation with the wild‐type rocF gene. Complemented strains also had restored arginase protein as determined by Western blot analysis. The complementation system could be successfully applied to multiple H. pylori strains. The intergenic region varied in length and sequence across 17 H. pylori strains, but the flanking‐3′ ends of the hp0203 and hp0204 coding regions were highly conserved. Inserting a cat cassette and wild‐type rocF into the intergenic region did not alter the ability of strain SS1 to colonize mice.

Conclusions:  This complementation strategy should greatly facilitate genetic experiments in H. pylori.
Deficiency in OGG1 Protects against Inflammation and Mutagenic Effects Associated with H. pylori Infection in Mouse
Authors: Touati Eliette , Michel Valérie , Thiberge Jean‐Michel , Avé Patrick , Huerre Michel , Bourgade Franck , Klungland Arne , Labigne Agnès
Published: September 2006

Background:  Helicobacter pylori infection is associated with gastric cancer. Study with the Big Blue mouse model has reported a mutagenic effect associated with the H. pylori infection, as a result in part of oxidative DNA damage. The present work investigates the consequences of a deficiency in the OGG1 DNA glycosylase, responsible for the excision of 8‐oxo guanine, on the inflammatory and genotoxic host response to the infection.

Materials and Methods:  Big Blue Ogg1–/– C57BL/6 mice were orally inoculated with H. pylori strain SS1 or vehicle only, and sacrificed after 1, 3, or 6 months. The serologic response, histologic lesions, mutant frequency, and spectra of mutations were assessed in the stomach and compared to what observed in the wild‐type (Wt) context.

Results:  Inflammatory lesions induced in the gastric mucosa of H. pylori‐infected mice, corresponding to a moderate gastritis, were less severe in Ogg1–/– than in Wt Big Blue mice. Analysis of antimicrobial humoral immunity exhibited a lower IgG2a serum level (Th1 response) after 6 months of infection in Ogg1–/– than in the Wt mice. In these conditions, the H. pylori‐SS1 infection in the Ogg1–/– mice did not induce a mutagenic effect at the gastric epithelial cells level, either after 3 or 6 months.

Conclusions:  The inactivation of the OGG1 DNA glycosylase in mouse leads to less severe inflammatory lesions and abolished the mutagenic effect at the gastric epithelial cells level, induced by the H. pylori infection. These data suggest for the OGG1deficiency a protective role against inflammation and genotoxicity associated to the H. pylori infection.
Monoclonal Gammopathy of Undetermined Significance and Russell Body Formation in Helicobacter pylori Gastritis
Authors: Wolkersdörfer Gernot W. , Haase Michael , Morgner Andrea , Baretton Gustavo , Miehlke Stephan
Published: September 2006

Background:  Infection by Helicobacter pylori has been linked to monoclonal gammopathy of undetermined significance (MGUS). MGUS is thought to develop due to chronic antigenic stimulation in people with a specific genetic predisposition.

Methods and Results:  We describe a patient presenting with dyspepsia associated with H. pylori‐related erosive gastritis. Histopathologic findings revealed infiltration with plasma cells containing accumulated condensed intercisternal immunoglobulins, the so‐called ‘Russell bodies’. In addition, MGUS was present with total immunoglobulins within the normal range but a significantly decreased serum concentration of IgG subtype 3. Molecular analyses demonstrated IgH formation, T‐cell receptor γ rearrangement, and alterations within the IgHG3 gene sequence. Following H. pylori eradication, gastritis and dyspepsia gradually resolved but MGUS persisted for at least 22 months.

Conclusions:  This is the first report to demonstrate that upon infection with H. pylori, an impaired secretory capacity of plasma cells due to specific molecular changes can present as Russell body gastritis. The molecular findings question a pathogenetic link between Russell bodies and H. pylori, but suggest genetic alterations in the immunoglobulin locus as the possible cause for both MGUS and Russell body gastritis.
Electrophoretic Deposition of YSZ Particles on Non‐Conducting Porous NiO–YSZ Substrates for Solid Oxide Fuel Cell Applications
Authors: Besra Laxmidhar , Compson Charles , Liu Meilin
Published: September 2006

This paper reports a method of performing electrophoretic deposition (EPD) on non‐conducting substrates overcoming the requirement of a conducting substrate through the use of porous substrates. The conductivity of the substrate is therefore no longer a limiting factor in the application of EPD. This method is applicable to the fabrication of thick or thin layers of ceramic or metal for various applications. As an example, thin and dense yttria‐stabilized zirconia (YSZ) layers have been deposited on a non‐conducting NiO–YSZ substrate by EPD from a non‐aqueous suspension. A solid oxide fuel cell constructed on these sintered bilayers exhibited power densities of 384 and 611 mW/cm2 at 750° and 850°C, respectively.
Internal Structure Evaluation of Three‐Dimensional Calcium Phosphate Bone Scaffolds: A Micro‐Computed Tomographic Study
Authors: Jongpaiboonkit Leenaporn , Halloran John W. , Hollister Scott J.
Published: September 2006

Micro‐computed tomography (μ‐CT) was used to examine the fidelity of three‐dimensional (3D) bioceramic scaffolds made from dicalcium phosphate dihydrate (DCPD) cement. The scaffolds were produced with a multi‐step indirect solid freeform fabrication method. Accuracy and fidelity were examined after each step. The pre‐tracing of the perimeter of a layer in the mold fabrication step caused the round‐off of the square channels from the design. However, the overall shape of the scaffold was not significantly different from the wax mold. There is relatively no change in the strut and the channel‐size measurements between the computer‐generated model and the molds fabricated by 3D printing. The change in volume fraction of DCPD cement scaffolds is higher than biphasic scaffolds due to the internal pores. These results demonstrated that μ‐CT is a very useful tool to analyze and evaluate the internal architectural of the complicated 3D scaffold‐fabrication process.
Synthesis of BaCu(B2O5) Ceramics and their Effect on the Sintering Temperature and Microwave Dielectric Properties of Ba(Zn1/3Nb2/3)O3 Ceramics
Authors: Kim Min‐Han , Lim Jong‐Bong , Kim Jae‐Chul , Nahm Sahn , Paik Jong‐Hoo , Kim Jong‐Hee , Park Kyeong‐Soon
Published: September 2006

BaCu(B2O5) ceramics were synthesized and their microwave dielectric properties were investigated. BaCu(B2O5) phase was formed at 700°C and melted above 850°C. The BaCu(B2O5) ceramic sintered at 810°C had a dielectric constant (ɛr) of 7.4, a quality factor (Q×f) of 50 000 GHz and a temperature coefficient of resonance frequency (τf) of −32 ppm/°C. As the BaCu(B2O5) ceramic had a low melting temperature and good microwave dielectric properties, it can be used as a low‐temperature sintering aid for microwave dielectric materials for low temperature co‐fired ceramic application. When BaCu(B2O5) was added to the Ba(Zn1/3Nb2/3)O3 (BZN) ceramic, BZN ceramics were well sintered even at 850°C. BaCu(B2O5) existed as a liquid phase during the sintering and assisted the densification of the BZN ceramic. Good microwave dielectric properties of Q×f=16 000 GHz, ɛr=35, and τf=22.1 ppm/°C were obtained for the BZN+6.0 mol% BaCu(B2O5) ceramic sintered at 875°C for 2 h.
Spark Plasma Sintering of Ca1−xSrxTiO3 Doped with Li2Si2O5
Authors: Li Ruixing , Tang Qing , Yin Shu , Omori Mamoru , Yamane Hisanori , Sato Tsugio
Published: September 2006

Spark plasma sintering (SPS) of Ca1−xSrxTiO3 was conducted with and without an Li2Si2O5 additive at 1170°C for 4 min. A single phase, Ca1−xSrxTiO3 solid solution was formed; moreover, the mechanical and dielectric properties were improved by adding 0.5 wt% Li2Si2O5. Conversely, in the absence of Li2Si2O5, a mixture of Ruddlesden–Popper phases Srn+1TinO3n+1 and rutile TiO2 was formed in addition to Ca1−xSrxTiO3 although a single phase Ca1−xSrxTiO3 could be formed via pressureless sintering at 1200°C for 2 h in air. These results suggested that Li2Si2O5 was useful even via an SPS technique to promote the mass transfer, and its optimum concentration was 0.5 wt%.
Stresses and Distortion Due to Green Density Gradients During Densification
Authors: Schoenberg Sam E. , Green David J. , Segall Albert E. , Messing Gary L. , Grader Abraham S. , Halleck Phillip M.
Published: September 2006

Finite element analysis (FEA) was performed on a bi‐layer cylindrical structure consisting of a low‐density layer on top of a high‐density layer. For this model, the layers used the shrinkage behavior, viscosity, and elastic properties of barium titanate determined for the 45% and 55% green densities. The stresses predicted by FEA showed good agreement with stresses predicted using analytical equations for a linear viscous bi‐layer cylinder. The model was then extended to use more complex density gradients measured by X‐ray computed tomography on a bi‐layer compact. In this case, the shrinkage behavior and viscosity properties were extrapolated from the experimental data. In the subsequent simulation, the stresses and strains were predicted during sintering. For the bi‐layer structure studied, a highly stressed region was identified on the free surface of the sintering compact and this was shown to lead to edge cracking during densification.
New Route to Synthesize Ultra‐Fine Zirconium Diboride Powders Using Inorganic–Organic Hybrid Precursors
Authors: Yan Yongjie , Huang Zhengren , Dong Shaoming , Jiang Dongliang
Published: September 2006

Ultra‐fine zirconium diboride (ZrB2) powders have been synthesized using inorganic–organic hybrid precursors of zirconium oxychloride (ZrOCl2·8H2O), boric acid, and phenolic resin as sources of zirconia, boron oxide, and carbon, respectively. The reactions were substantially completed at a relatively low temperature (∼1500°C). The synthesized powders had a smaller average crystallite size (<200 nm), a larger specific surface area (∼32 m2/g), and a lower oxygen content (<1.0 wt%), which were superior to some commercially available ZrB2 powders. The thermodynamic change in the ZrO2–B2O3–C system was mainly studied by thermogravimetric and differential thermal analysis. The crystallite size and morphology of the synthesized powders were characterized by transmission electron microscopy and scanning electron microscopy.
Positive patch test reactions to allergens of the dental series and the relation to the clinical presentations
Authors: Khamaysi Ziad , Bergman Reuven , Weltfriend Sara
Published: September 2006

The clinical manifestations of contact allergic dermatitis to dental materials are not uniform. This study was performed to detect the frequent allergens in the dental series associated with contact dermatitis and to define the causal relationship between the different allergens and the relevant clinical presentations. Between the years 2000 and 2004, 134 patients, aged 20–80 years, were patch tested. 121 patients were included in the study. The most frequent oral manifestations were cheilitis and perioral dermatitis (25.6%), burning mouth (15.7%), lichenoid reaction (14.0%), and orofacial granulomatosis (10.7%). 18 (14.9%) patients were dental personnel, all of whom suffered from hand dermatitis. The common allergens detected included goldsodiumthiosulphate (14.0%), nickel sulfate (13.2%), mercury (9.9%), palladium chloride (7.4%), cobalt chloride (5.0%), and 2‐hydroxyethyl methacrylate (5.8%). Positive reactions to metals were frequent in all the different clinical variants, and no specific association between a specific clinical presentation and a particular allergen was found. Allergy to mercury was not a significant factor contributing to the pathogenesis of oral lichenoid reactions. However, a strong association with contact allergy to mercury in dental fillings was found in 2 patients with orofacial granulomatosis.
Miconidin and miconidin methyl ether fromPrimula obconicaHance: new allergens in an old sensitizer
Authors: Paulsen Evy , Christensen Lars P. , Andersen Klaus Ejner
Published: September 2006

Several chemical and clinical observations have suggested the presence of at least one more allergen in addition to primin inPrimula obconica. The aim of this study was to investigate the allergenicity of the primin precursor miconidin and the related miconidin methyl ether, both isolated fromP. obconica. 12 primin‐positive persons were patch tested with miconidin 0.01% petrolatum (pet.), miconidin in 96% ethanol incorporated into 0.01% pet., and miconidin methyl ether 1.0% pet. All persons were positive to miconidin 0.01% pet., with the strength of reactions very similar to those of the individual primin reactions, and remained inexplicably negative while testing with miconidin in 96% ethanol and pet., while miconidin methyl ether elicited 7 positive reactions. Although both miconidin and miconidin methyl ether may be allergenic only due to their conversion to primin in the skin, the presence of these substances nevertheless has to be taken into account when assessing the allergenicity of newP. obconicacultivars.
High‐performance liquid chromatography analysis of rubber allergens in protective gloves used in health care
Authors: Bergendorff Ola , Persson C. , Hansson C.
Published: September 2006

A high‐performance liquid chromatography (HPLC) method developed for analysis of zinc dithiocarbamates was validated and used to perform a survey of disposable medical gloves used in southern Sweden. The gloves were extracted with acetone at room temperature for 10 min by shaking. The extracts were injected into a polyether ether ketone lined HPLC column, and peaks were analysed by a diode‐array detector. The survey shows that of 19 gloves analysed, 10 contained zinc diethyldithiocarbamate (0.070–3.5 mg/g), 3 contained zinc pentamethylenedithiocarbamate (1.0–4.3 mg/g), 4 contained zinc dibutyldithiocarbamate (0.9–1.1 mg/g), and 2 contained 2‐mercaptobenzothiazole (0.005–0.008 mg/g). None of them contained thiurams.
Intrinsic characteristics of contact and respiratory allergens influence production of polarizing cytokines by dendritic cells
Authors: Toebak Mascha J. , Moed Heleen , Von Blomberg Mary B. E. , Bruynzeel Derk P. , Gibbs Susan , Scheper Rik J. , Rustemeyer Thomas
Published: September 2006

Type 1 and type 2 cytokines are primary mediators in contact allergy and aeroallergen‐mediated disorders, respectively. For both types of disease, dendritic cells (DCs) are pivotal in initiating immune hyperresponsiveness. We studied whether contact and respiratory allergens possess intrinsic capacities to polarize DC towards DC1 and DC2 functions, independent of environmental factors. Human monocyte‐derived DCs were exposed to the positive controls [type 1: lipopolysaccharide (LPS) + interferon‐γ; type 2: LPS + prostaglandin E2], contact allergens [2,4‐dinitrochlorobenzene (DNCB), oxazolone (OXA), and nickel sulfate (NiSO4)], and respiratory allergens [trimellitic anhydride (TMA) and the protein allergen derived from Dermatophagoides pteronyssinus (Der p1)]. The polarizing potentials of the allergens on DCs were determined by the secretion of type 1 [tumour necrosis factor‐α (TNF‐α), CXCL10, and interleukin (IL)‐12p70] and type 2 (IL‐10) cytokines. The contact allergens, DNCB and OXA, induced strict type 1 DC polarization, whereas the respiratory allergens, TMA and Der p1, showed strict type 2 DC polarization. The contact allergen, NiSO4, induced both DC1 (TNF‐α and CXCL10 production) and DC2 (decreased IL‐12p70/IL‐10 ratio) features. These results support the view that allergens have an intrinsic capacity to skew immune responses at the DC level, irrespective of local factors such as those determined by cutaneous or mucosal epithelial microenvironments.
Contact allergy to (meth)acrylates in the dental series in southern Sweden: simultaneous positive patch test reaction patterns and possible screening allergens
Authors: Goon Anthony T. J. , Isaksson Marléne , Zimerson Erik , Goh Chee Leok , Bruze Magnus
Published: September 2006

Contact allergy to dental allergens is a well‐studied subject, more so among dental professionals than dental patients. 1632 subjects had been patch tested to either the dental patient series or dental personnel series at the department of Occupational and Environmental Dermatology, Malmö, Sweden. Positive patch tests to (meth)acrylate allergens were seen in 2.3% (30/1322) of the dental patients and 5.8% (18/310) of the dental personnel. The most common allergen for both groups was 2‐hydroxyethyl methacrylate (2‐HEMA), followed by ethyleneglycol dimethacrylate (EGDMA), triethyleneglycol dimethacrylate, and methyl methacrylate. 47 (29 dental patients and 18 dental personnel) out of these 48 had positive patch tests to 2‐HEMA. All 30 subjects who had a positive reaction to EGDMA had a simultaneous positive reaction to 2‐HEMA. One dental patient reacted only to 2,2‐bis[4‐(2‐hydroxy‐3‐methacryloxypropoxy) phenyl]propane (bis‐GMA). From our data, screening for (meth)acrylate contact allergy with 2‐HEMA alone would have picked up 96.7% (29/30) of our (meth)acrylate‐allergic dental patients and 100% (18/18) of our (meth)acrylate‐allergic dental personnel. The addition of bis‐GMA in dental patients would increase the pick‐up rate to 100%.