bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Helicobacter pylori‐Induced Gastritis and the Effect of H. pylori Eradication in Patients with Chronic Idiopathic Thrombocytopenic Purpura
Authors: Ando Takafumi , Tsuzuki Tomoyuki , Mizuno Tomokazu , Minami Masaaki , Ina Kenji , Kusugami Kazuo , Takamatsu Junki , Adachi Kouichi , El‐Omar Emad , Ohta Michio , Goto Hidemi
Published: September 2004

Background.  The association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been reported widely. We investigated the prevalence of H. pylori infection, its virulence profile and the effectiveness of its eradication in patients with ITP.

Materials and Methods.  Twenty patients with ITP, 20 with peptic ulcer (10 gastric ulcer (GU), 10 duodenal ulcer (DU)) and 20 with NUD were studied. The virulence profile of the strains was assessed by genotyping for cagA, vacA, iceA, and hpyIIIR/hrgA and by assaying for IL‐8 and DNA fragmentation after incubation with AGS cells. Infected patients and two uninfected ITP patients received triple therapy and platelets were counted before and 1 month, 6 months, 1 year, and 2 years after eradication therapy.

Results.  H. pylori infection was found in 17 ITP (85%), 20 ulcer (100%) and 13 NUD (65%) patients. Biopsies and strains were collected from five ITP, 20 ulcer and 13 NUD patients. The ITP patients had a pangastritis or corpus‐predominant gastritis pattern. All H. pylori isolates, from ITP, ulcer and NUD patients, were cagA+ and vacA s1/m1, and did not differ in levels of IL‐8 induction or DNA fragmentation. Fifteen ITP (88%) and 17 ulcer (85%) patients had successful eradication of H. pylori. Ten of these 15 (67%) H. pylori‐eradicated ITP patients had platelet recovery. There was no significant change in platelet count in the two ITP patients in whom eradication failed or in the two originally H. pylori‐uninfected ITP patients, or in the treated ulcer patients. Age at onset of ITP was the main determinant of platelet recovery: 100% of patients diagnosed after the age of 60 recovered compared with only 22% of those diagnosed before 50.

Conclusions.  H. pylori‐infected ITP patients have a corpus‐predominant pattern of gastritis but the virulence profile of their strains does not differ from that of ulcer or NUD patients. Eradication of H. pylori infection is a good therapeutic option for some patients with chronic ITP, especially for those who develop ITP in older age.
Role of Noninvasive Tests (13C‐Urea Breath Test and Stool Antigen Test) as Additional Tools in Diagnosis of Helicobacter Pylori Infection in Patients with Atrophic Body Gastritis
Authors: Lahner Edith , Vaira Dino , Figura Natale , Pilozzi Emanuela , Pasquali Amelia , Severi Carola , Perna Federico , Fave Gianfranco Delle , Annibale Bruno
Published: September 2004

Background.  Detection of Helicobacter pylori infection in atrophic body gastritis (ABG) is difficult, as during progression of body atrophy, H. pylori disappears.

Aim.  To increase the diagnostic yield of detection of active H. pylori infection in atrophic body gastritis patients by using noninvasive tests such as 13C‐Urea Breath Test (13C‐UBT) and H. pylori stool antigen test (HpSA) would be useful.

Patients.  27 consecutive patients with newly‐diagnosed atrophic body gastritis (19F/7M, age 27–73 years).

Methods.  Gastroscopy with biopsies (antrum n = 3, body n = 3) and histology according to updated Sydney system, H. pylori IgG serology, 13C‐UBT, and HpSA.

Results.  All tests used in the diagnosis of H. pylori infection were in agreement in 9/27 atrophic body gastritis patients (33.3%), being all positive in four (14.8%) and all negative in five patients (18.5%). Ten of the 27 (37%) patients were Giemsa stain‐positive and serology‐positive (group I). Seventeen of the 27 (63%) patients were Giemsa stain‐negative: 5/17 with positive serology (group II) and 12/17 with negative serology (group III). In group I, 5/10 (50%) were 13C‐UBT positive and 4/10 (40%) HpSA positive. In group II, two patients were 13C‐UBT positive, but all were HpSA negative. Also in group III, all patients were HpSA negative, but one had a positive 13C‐UBT.

Conclusions.  In atrophic body gastritis patients, neither 13C‐UBT nor HpSA per se add useful information regarding active H. pylori infection, but these noninvasive tests may be important in combination with histology and serology to define the H. pylori status in some atrophic body gastritis patients.
Melanoidin, a Food Protein‐Derived Advanced Maillard Reaction Product, Suppresses Helicobacter pylori in vitro and in vivo
Authors: Hiramoto Shigeru , Itoh Kazuro , Shizuuchi Satomi , Kawachi Yasuji , Morishita Yoshirou , Nagase Masao , Suzuki Yoshio , Nobuta Yukio , Sudou Yuhshi , Nakamura Osamu , Kagaya Imae , Goshima Hideo , Kodama Yoshikatsu , Icatro Faustino C. , Koizumi Wasaburo , Saigenji Katsunori , Miura Soichiro , Sugiyama Toshiro , Kimura Nobutake
Published: September 2004

Background.  Extracellular urease proteins located on the surface of Helicobacter pylori are gastric mucin‐targeted adhesins, which play an important role in infection and colonization to the host. In this study we have determined the inhibitory activity of a variety of melanoidins, protein‐derived advanced Maillard reaction products, ubiquitously found in heat‐treated foods, on urease‐gastric mucin adhesion. In addition, we have determined the anticolonization effect of melanoidin I, prepared by the Maillard reaction between casein and lactose, in an animal model and in human subjects infected with this bacterium.

Methods.  The inhibitory activity of each compound was determined by a competitive binding assay of labeled gastric mucin to plate‐immobilized urease. Melanoidin I was used in an in vivo trial using euthymic hairless mice as an infection model. Melanoidin I was consumed for 8 weeks by subjects infected with H. pylori. The [13C] urease breath test and H. pylori‐specific antigen in the stool (HpSA) test were performed on subjects at week 0 and week 8.

Results.  A variety of food protein‐derived melanoidins strongly inhibited urease‐gastric mucin adhesion in the concentration range of 10 µg/ml to 100 µg/ml. In particular, melanoidin I significantly (p < .05) suppressed colonization of H. pylori in mice when given for 10 weeks via the diets. Eight weeks daily intake of 3 g melanoidin I significantly (p < .05) decreased the optical density of HpSA in subjects.

Conclusion.  Foods containing protein‐derived melanoidins may be an alternative to antibiotic‐based therapy to prevent H. pylori that combines safety, ease of administration and efficacy.
Selective and Effective Bactericidal Activity of the Cobalt (II) Cation against Helicobacter pylori
Authors: Bruggraber Sylvaine F. A. , French Gary , Thompson Richard P. H. , Powell Jonathan J.
Published: September 2004

Background.  Although the anti‐Helicobacter pylori activity of bismuth is well established, the therapeutic potential of other metal ions against the organism is not known.

Materials and Methods.  We measured the minimum inhibitory concentrations of a series of metal ions, including several cobalt (II) compounds against four type strains and seven clinical isolates of H. pylori using three standard broth culture media and a defined medium. Other intestinal bacteria were also investigated for specificity of action.

Results.  Cobalt chloride had marked activity against H. pylori (minimum inhibitory concentration range was 0.03–1.0 mg/l). The effect was specific because other transition metals had no effect and other intestinal bacteria were not affected by cobalt chloride. Activity was attributable to free cobalt ions as ligands inhibited activity in proportion to their affinity for the ions. Inhibition of cobalt activity was also observed in the presence of nickel, in a dose dependent fashion. However, cobalt activity was not directed towards the nickel‐dependent urease enzyme because its effect was similar in wild‐type and urease negative mutant strains of H. pylori. Finally, the viability of H. pylori was reduced at the same rate with 2 mg/l cobalt as with 1 mg/l amoxicillin.

Conclusions.  Cobalt competes for nickel in its acquisition by H. pylori, but mediates toxicity in a nonurease dependent fashion. As cobalt MIC is similar to some antibiotics and 10 to a hundred times lower than for bismuth, cobalt may represent an effective form of therapy for H. pylori infection.
Open, Randomized Multicenter Comparative Trial of Rabeprazole, Ofloxacin and Amoxicillin Therapy for Helicobacter pylori Eradication: 7 vs. 14 Day Treatment
Authors: Bosques‐Padilla Francisco J. , Garza‐González Elvira , Calderón‐Lozano Irma E. , Reed‐SanRoman Gerardo , De Ariño Suárez Mauricio , Valdovinos‐Díaz Miguel Á. , Orozco‐Gámiz Antonio , Blancas‐Valencia Juan M. , Tamayo‐de la Cuesta José L.
Published: September 2004

Background.  Because of the increasing resistance to clarithromycin and metronidazole, two of the antibiotics used for the eradication of Helicobacter pylori, new therapeutic alternatives are needed. The aim of this study was to determine the efficacy of a randomized, comparative trial of 7 vs. 14‐day triple treatment with rabeprazole, ofloxacin and amoxicillin for H. pylori eradication.

Material and Methods.  The present authors studied 76 dyspeptic patients infected with H. pylori diagnosed by both histology and a rapid urease test. Patients were randomized to receive rabeprazole (20 mg b.i.d.), plus ofloxacin (400 mg b.i.d.) and amoxicillin (1000 mg b.i.d.) for 7 days (group 1) vs. 14 days (group 2) and were followed by 6 weeks. Eradication was assessed 4 weeks after completing the course of study treatment by the 14C‐urea breath test. Per protocol and intention‐to‐treat eradication rates were determined.

Results.  For the intention to treat analysis, the eradication rate was 62.2% for group 1 and 92.3% for group 2 (p = .004). For the per protocol analysis, eradication rate for group 1 was 63.9% and for group 2 was 97.3% (p = .001).

Conclusions.  Triple therapy with rabeprazole, amoxicillin and ofloxacin by 14 days was efficient for H. pylori eradication and therefore deserves further study. The same regimen prescribed for 7 days had a significantly lower and unacceptable cure rate and should not be used.
Detection of Helicobacter ganmani‐Like 16S rDNA in Pediatric Liver Tissue
Authors: Tolia Vasundhara , Nilsson Hans‐Olof , Boyer Kimberly , Wuerth Anne , Al‐Soud Waleed Abu , Rabah Raja , Wadström Torkel
Published: September 2004

Background.  To determine the presence of Helicobacter species in the liver biopsy specimens from children with various chronic liver diseases as data in adult literature suggests a possible role of these bacteria in their pathogenesis.

Materials and methods.  Paraffin sections of 61 liver biopsies of pediatric patients with miscellaneous diseases and autopsy liver tissue from 10 control subjects with no evidence of preexisting liver disease were examined for the presence of Helicobacter species by a genus‐specific seminested polymerase chain reaction (PCR) assay. PCR–products of positive samples were further characterized by denaturing gradient gel electrophoresis (DGGE) and DNA‐sequence analysis. Based on those results, a seminested PCR assay for H. ganmani was developed and applied to the samples.

Results.  On analysis, 40/61 patient samples were positive in the genus‐specific Helicobacter PCR and 4/10 from the control group. The nucleotide sequences of 16S rDNA fragments were 99–100% similar to mainly Helicobacter sp. ‘liver’ and H. ganmani. PCR‐products similar to H. canis and H. bilis were also found. The 16S rDNAs of control specimens showed similarity to Helicobacter sp. ‘liver’. In the H. ganmani‐specific PCR analysis 19 patients, but none of the controls, were positive.

Conclusions.  Amplified Helicobacter 16S rDNAs were related to Helicobacter sp. ‘liver’ or H. ganmani in liver biopsy specimens of pediatric patients. The possible significance of Helicobacter species in pediatric liver diseases needs to be evaluated further in prospective studies.
Identification of a Novel Mutation Affecting Domain V of the 23S rRNA Gene in Helicobacter pylori
Authors: Toracchio Sonia , Aceto Gitana M. , Mariani‐Costantini Renato , Battista Pasquale , Marzio Leonardo
Published: September 2004

Background.  This study analyzes clarithromycin resistance status and 23S rRNA gene mutations in Helicobacter pylori strains from Central Italian patients.

Materials and methods.  H. pylori strains from 235 dyspeptic patients (205 with no history of clarithromycin exposure and 30 referred for failure of eradication therapy) were tested for clarithromycin resistance by screening agar method and E‐test. Resistant strains were analyzed for mutations of the 23S rRNA gene by PCR‐RFLP and sequencing.

Results.  Primary resistance was observed in strains from 43/205 (21%) patients with no history of clarithromycin exposure and secondary resistance in 30/30 (100%) strains from previously treated patients. A single mutant strain was detected in 54/73 (74%) cases, a mixture of one or more mutant(s) plus the wild type in the remaining 19/73 (26%) cases. One 23S rRNA gene mutation (A→T transversion at nucleotide 2144) in the peptidyltransferase region of domain V was novel.

Conclusions.  This study shows: (a) a high prevalence of H. pylori strains with primary or secondary clarithromycin resistance in an urban area of Central Italy; (b) colonization by both mutant and wild‐type H. pylori in the same patient; (c) a novel variant of the H. pylori 23S rRNA gene.
Helicobacter pylori HP1034 (ylxH) is required for motility
Authors: Van Amsterdam Karin , Van Der Ende Arie
Published: September 2004

Background.  Helicobacter pylori motility is essential for the colonization and persistence in the human gastric mucosa. So far, more than 50 genes have been described to play a role in flagellar biosynthesis. H. pylori YlxH (HP1034) is annotated as an ATP‐binding protein. However, H. pylori YlxH shows similarity to proteins involved in the flagellar biosynthesis of other bacterial species. Moreover, H. pylori ylxH is found adjacent to genes involved in flagellar biosynthesis in the sequenced genomes of H. pylori 26695 and J99. We therefore aimed to determine the role of YlxH in H. pylori motility.

Materials and methods.  Motility, flagellar biosynthesis and transcriptional regulation of genes encoding flagellar proteins was compared between H. pylori 11A and a knockout of ylxH in H. pylori 11A.

Results.  The ylxH knockout in H. pylori 11A was nonmotile on soft agar plates, whereas H. pylori 11A was motile. Furthermore, the H. pylori 11A ylxH knockout lacked flagella, while H. pylori 11A possessed two to three flagella. Transcription of H. pylori flaG (HP0751), fliM (HP1031) and fliA (HP1032) was reduced in the H. pylori 11A ylxH¯ knockout, whereas transcription of flaA (HP0601) was not altered. However, Western blot analysis showed substantially reduced amounts of the major flagellin subunit FlaA in the H. pylori 11A ylxH knockout compared to H. pylori 11A.

Conclusions.  H. pylori YlxH is essential for the assembly of flagella and hence for the motility of H. pylori.
Effect of H. pylori on the Expression of TRAIL, FasL and their Receptor Subtypes in Human Gastric Epithelial Cells and their Role in Apoptosis
Authors: Martin Jan Hendrik , Potthoff Andrej , Ledig Susanne , Cornberg Markus , Jandl Oliver , Manns Michael P. , Kubicka Stefan , Flemming Peer , Athmann Christoph , Beil Winfried , Wagner Siegfried
Published: September 2004

Background and Aims.  In the human stomach expression of TNF‐related apoptosis inducing ligand (TRAIL) and its receptors and the modulatory role of Helicobacter pylori are not well described. Therefore, we investigated the effect of H. pylori on the expression of TRAIL, FasL and their receptors (TRAIL‐R1‐R4, Fas) in gastric epithelial cells and examined their role in apoptosis.

Materials and Methods.  mRNA and protein expression of TRAIL, FasL and their receptors were analyzed in human gastric epithelial cells using RT‐PCR, Western blot, and immunohistochemistry. Gastric epithelial cells were incubated with FasL, TRAIL and/or H. pylori, and effects on expression, cell viability and epithelial apoptosis were monitored. Apoptosis was analyzed by histone ELISA, DAPI staining and immunohistochemistry.

Results.  TRAIL, FasL and their receptor subtypes were expressed in human gastric mucosa, gastric epithelial cell primary cultures and gastric cancer cells. TRAIL, FasL and H. pylori caused a time‐ and concentration‐dependent induction of DNA fragmentation in gastric cancer cells with synergistic effects. In addition, H. pylori caused a selective up‐regulation of TRAIL, TRAIL‐R1 and Fas mRNA and protein expression in gastric cancer cells.

Conclusions.  Next to FasL and Fas, TRAIL and all of its receptor subtypes are expressed in the human stomach and differentially modulated by H. pylori. TRAIL, FasL and H. pylori show complex interaction mediating apoptosis in human gastric epithelial cells. These findings might be important for the understanding of gastric epithelial cell kinetics in patients with H. pylori infection.
The rdxA Gene Plays A More Major Role Than frxA Gene Mutation in High‐level Metronidazole Resistance of Helicobacter pylori in Taiwan
Authors: Yang Yao‐Jong , Wu Jiunn‐Jong , Sheu Bor‐Shyang , Kao Ai‐Wen , Huang Ay‐Huey
Published: September 2004

Background.  Metronidazole‐resistant H. pylori associating with mutations of rdxA or frxA is still a debated topic. This study investigates whether rdxA and frxA mutations of H. pylori accounted for the high MIC value (≥ 64 µg/ml) of metronidazole (Mtz).

Material and Methods.  From 126 clinical H. pylori isolates, we examined 14 Mtz‐sensitive, 18 Mtz‐resistant H. pylori, and eight pairs of Mtz‐sensitive and Mtz‐resistant colonies simultaneously present within a single gastric biopsy. The paired strains from one single biopsy were proven identical by PCR‐RFLP. MICs of Mtz were checked by the E‐test and agar dilution method. The mutations of rdxA and frxA sequencing were matched with the Mtz‐susceptible ATCC 26695 and J99.

Results.  There were 89% (16/18) of Mtz‐resistant isolates with mutation of RdxA. Half of the 14 Mtz‐sensitive strains, all without mutation of RdxA, still contained truncation of FrxA. Within the paired isolates from a single biopsy, rdxA mutation (86%) was more common than frxA mutation (43%) in those isolates with high‐level Mtz‐resistant H. pylori. RdxA truncation was more prevalent in Mtz‐resistant strains with high MICs than in those with low to moderate MICs (75% vs. 20%, p = .01, OR: 12, 95% CI: 1.8–81.7).

Conclusion.  Mutations in the rdxA gene rather than the frxA gene generally determine a high MIC level of Mtz‐resistant H. pylori in Taiwan.
Temporal changes in fishing motivation among fishing club anglers in the United States
Authors: Schramm H. L. , Gerard P. D.
Published: September 2004

Responses from freshwater anglers (n = 4287) to a nationwide survey of the US fishing club members were used to assess differences in the importance of 16 fishing motivation items between 1987 and 1997, dates that preceded and followed a period of substantial decline in recreational fishing participation in the US. Comparison of respondents’ motivations for fishing in 1997 and 10 years earlier indicated consistency in the paramount importance of being outdoors, relaxation and the experience of the catch. However, the importance of family recreation and being with friends in 1987 were replaced by escape items in 1997. Anglers with fewer dependents and living in areas with higher population density were more likely to decrease the importance of family recreation. Younger anglers were more likely to decrease the importance of being with friends. Anglers who had higher household income, fished more and had higher fishing expenditures were more likely to decrease the importance of obtaining fish to eat. The results of this study suggest that managers should be less concerned about angler opposition to liberal regulations that allow anglers to harvest fish, and that heightened efforts to recruit and retain recreational anglers, which presently focus on family recreation, should be broadened to include outdoor experience, relaxation and escape aspects of fishing.
Discards from the commercial gillnet fishery for dusky flathead, Platycephalus fuscus, in New South Wales, Australia: spatial variability and initial effects of change in minimum legal length of target species
Authors: Gray C. A. , Johnson D. D. , Young D. J. , Broadhurst M. K.
Published: September 2004

A scientific observer programme was used to quantify the composition and magnitude of discards in the gillnet fishery for dusky flathead, Platycephalus fuscus (Cuvier), in three barrier estuaries in New South Wales, Australia, during the 2001 fishing season. Regulations only permit the retention of legal‐sized dusky flathead and legal‐sized blue swimmer crab, Portunus pelagicus L., and mud crab, Scylla serrata (Forskål); all other organisms were discarded. Sampling was stratified into two time periods; before and after 1 July 2001 which coincided with the increase in the minimum legal length (MLL) of dusky flathead from 33 to 36 cm total length (TL). Eighty one catches were sampled, yielding 38 finfish species and two portunid crab species. Legal‐sized dusky flathead were the most abundant organism captured, accounting for 23–47% by number and 34–54% by weight of the mean observed catch depending on the estuary and survey period, with a mean catch of 25–59 flathead weighing 13–25 kg per fishing‐night. Species composition and relative abundance of catches differed among estuaries, but not between sampling periods. Predominant bycatch species included legal and undersize blue swimmer crab, sea mullet, Mugil cephalus L., luderick, Girella tricuspidata (Quoy & Gaimard), bream, Acanthopagrus australis (Günther) and yellowfin leatherjacket, Meuschenia trachylepis (Günther). These five species accounted for 82% of total bycatch by number and 71% by weight, pooled across the three estuaries. More crabs were retained than discarded, with retained legal‐size crabs (byproduct) accounting for 16% of total bycatch by number and 13% by weight, with an average of 5–22 crabs weighing 1–6 kg being caught per fishing‐night, depending on the estuary. Overall, 7% of dusky flathead captured (number) were below the MLL of 36 cm and discarded, suggesting the nets as currently configured may be relatively selective in catching legal‐size flathead. However, 41% of dusky flathead were <40 cm TL, indicating that if the MLL for this species is increased to this length as proposed, new nets must be introduced into the fishery. The findings are discussed in terms of making the flathead fishery more sustainable, including alternative management strategies for the fishery.
Fish assemblages of perennial floodplain ponds of the Sacramento River, California (USA), with implications for the conservation of native fishes
Authors: Feyrer F. , Sommer T. R. , Zeug S. C. , O'Leary G. , Harrell W.
Published: September 2004

To assess the likelihood of enhancing native fish populations by means of floodplain restoration projects, habitat characteristics and fish assemblages of seven perennial floodplain ponds in Yolo Bypass, the primary floodplain of the Sacramento River, California (USA), were examined during summer 2001. Although all ponds were eutrophic, based upon high chlorophyll a or dissolved nutrient concentrations, relatively large shallow ponds generally exhibited higher specific conductivity and dissolved phosphorus concentrations than small deep ponds, which exhibited greater water transparency and total dissolved nitrogen concentrations. Using multiple gear types, 13 688 fishes comprising 23 species were collected. All ponds were dominated by alien fishes; only three native species contributing <1% of the total number of individuals and <3% of overall biomass were captured. Fish assemblage structure varied among ponds, notably between engineered vs. natural ponds, and was related to specific conductance, total dissolved solids and water transparency.
Environmental influences on largemouth bass Micropterus salmoides populations in shallow Nebraska lakes
Authors: Paukert C. P. , Willis D. W.
Published: September 2004

The influence of environmental variables on largemouth bass Micropterus salmoides (Lacépède) populations in 22 shallow (mean depth 1.0–2.9 m) Nebraska lakes was evaluated. Largemouth bass exhibited density‐dependent size structure and growth, but not condition. Total annual mortality averaged only 30%. Deeper lakes contained low density largemouth bass populations with a high proportion of fish >380 mm, whereas larger lakes with little submerged vegetation had faster growth. The proportion of largemouth bass >380 mm and relative abundance tended to increase with emergent vegetation coverage. More stable recruitment was evident in shallower lakes with increased emergent vegetation coverage. Strong year classes were associated with cooler September air temperatures. Largemouth bass populations exhibited density‐dependent effects in lakes up to 332 ha. Lake depth, emergent vegetation and autumn air temperatures may influence largemouth bass populations more than previously suggested.
Effects of hot dry summers on the loss of Atlantic salmon, Salmo salar, from estuaries in South West England
Authors: Solomon D. J. , Sambrook H. T.
Published: September 2004

Salmon, Salmo salar L., were radio tagged in four estuaries in South West England. At medium to high summer flows, most salmon entering the river did so within 10 days of tagging. Lower flows were associated with an increased tendency for fish to remain in tidal water for a protracted period, and for those delayed fish to fail to enter the river. The delay was correlated with low freshwater flow, but it was concluded that high water temperature, and in some situations low dissolved oxygen, were likely to be the major influences. The causes of failure to enter the river by the delayed fish include lethally low levels of oxygen in some situations, but a major factor may be missed physiological opportunity. Implications in terms of water resource management, fisheries management and climate change are discussed.
Elevated CO2effects on decomposition processes in a grazed grassland
Authors: Allard Vincent , Newton Paul C. D. , Lieffering Mark , Soussana Jean‐Francois , Grieu Phillipe , Matthew Cory
Published: September 2004

The effects of elevated atmospheric CO2(475 μL L−1) onin situdecomposition of plant litter and animal faecal material were studied over 2 years in a free air CO2enrichment (FACE) facility. The pasture was grazed by sheep and contained a mixture of C3and C4grasses, legumes and forbs. There was no effect of elevated CO2on decomposition within plant species but marked differences between species with faster decomposition in dicots; a group that increased in abundance at elevated CO2. Decomposition of mixed herbage root material occurred at a similar rate to that of leaf litter suggesting that any CO2‐induced increase in carbon allocation to roots would not reduce rates of decomposition. Sheep faeces resulting from a ‘high‐CO2diet’ decomposed significantly slower during summer but not during winter. The overall outcome of these experiments were explored using scenarios that took account of changes in botanical composition, allocation to roots and the presence of herbivores. In the absence of herbivores, elevated CO2led to a 15% increase in the rate of mass loss and an 18% increase in the rate of nitrogen (N) release. In the presence of herbivores, these effects were partially removed (11% increase in rate of mass loss and 9% decrease in N release rate) because of the recycling occurring through the animals in the form of faeces.
The effects of elevated CO2and temperature on the resistance of winter‐dormant birch seedlings (Betula pendula) to hares and voles
Authors: Kuokkanen K. , Niemelä P. , Matala J. , Julkunen‐Tiitto R. , Heinonen J. , Rousi M. , Henttonen H. , Tahvanainen J. , Kellomäki S.
Published: September 2004

The effects of elevated CO2and temperature on the resource allocation pattern and resistance against mammalian herbivores of silver birch (Betula pendulaRoth) were studied. Birch seedlings were grown through two growing seasons in closed‐top chambers exposed to four different treatments: ambient CO2and temperature, elevated atmospheric CO2(700 ppm) and ambient temperature, elevated temperature (+3°C above ambient) and ambient CO2, and a combination of elevated CO2and temperature. After winter hardening of the seedlings, the growth of the seedlings was measured and the concentration of secondary compounds such as phenolics and papyriferic acid determined. The top parts of the stem were fed to hares, and the basal parts of the same stems were offered to voles.

Elevated CO2increased the height and basal diameter of the shoots, shoot biomass and total biomass of the seedlings but did not have any effect on secondary chemistry. Elevated temperature increased the height and shoot biomass, but did not have a significant effect on the total biomass of the seedlings. Elevated temperature decreased the concentration of condensed tannins and their precursor, (+)‐catechin, in the top part of the stems, but only the concentration of (+)‐catechin in the basal part of the stems. There were no significant interactive effects between CO2and temperature on phenolics in the stems, while the concentration of papyriferic acid showed significant interaction in the top part of the stems. This indicates high accumulation of papyriferic acid in ambient CO2under increased temperature. Consequently, elevated temperature increased the resistance of birch against hares, but did not affect the resistance of the basal parts of the same birches to voles. Our results indicate that the predicted climatic change will not necessarily lead to increased browsing damage by the mountain hare and the field vole to silver birch.
Plant species richness and composition of heathland relics in north‐western Belgium: evidence for a rescue‐effect?
Authors: Piessens Katrien , Honnay Olivier , Nackaerts Kris , Hermy Martin
Published: September 2004

Aim  To study the effects of the degree of fragmentation of heathland patches on their species richness and species composition, and to infer the ecological mechanisms behind the observed patterns.

Location  The heathland patches of the north‐western part of Flanders, Belgium. During the last 200 years, the heathland area in this study area has been reduced from c. 10,000 to c. 40 ha, yielding c. 150 small and highly isolated relic fragments.

Methods  Different isolation measures were calculated for each of the 153 inventoried heathland patches. The influence of isolation, area and habitat diversity on species richness was investigated using correlation techniques. Community composition of the patches was tested for nestedness, and the mechanisms potentially underlying this pattern were determined.

Results and main conclusions  Both the analyses at the species richness and community composition level yielded evidence for a positive species–area relation. This relation was not caused by higher habitat heterogeneity in larger patches. Patch isolation, measured in different ways, however seemed much more important in explaining species richness and community composition than fragment area. Our results indicate that area effects are overcompensated by the rescue‐effect: if a patch is close to other patches, species can disperse between them and prevent the species from going extinct. Species having a short living seed bank were also more sensitive to isolation than species with a long living seed bank, indicating that the latter most probably depend on the seed bank to survive periods when environmental conditions are harsh. Analogously to the spatial rescue‐effect, the existence of a persistent seed bank may lead to a sort of temporal rescue‐effect, where the extinction of a plant species is prevented through survival in the seed bank of a patch.
Modelling pollen sedimentation in Danish lakes at c.ad 1800: an attempt to validate the POLLSCAPE model
Authors: Nielsen Anne Birgitte
Published: September 2004

Aims  To validate the POLLSCAPE simulation model of pollen dispersal and deposition, and evaluate the effect of factors such as pollen productivity, wind speed and regional plant abundance, using a data set of ad 1800 pollen assemblages and historical land cover data.

Location  Denmark.

Methods  ad 1800 land cover from historical maps is digitized for 2000 m radii around 30 Danish lakes (3.5–33 ha). The simulation model POLLSCAPE is used to predict sedimentary pollen assemblages in the lakes from the plant abundance data inferred from these maps, with different model parameter settings for wind speed, pollen productivity, regional pollen loading, etc. The model predictions are compared with observed ad 1800 pollen assemblages from the lake sediment records. Furthermore, pollen productivity is estimated from the ad 1800 pollen and vegetation data using the Extended R‐value model.

Results  Generally the model reproduces the patterns in the observed pollen assemblages, and for most pollen types there are significant correlations between observed and predicted pollen proportions. The pollen proportions predicted by the POLLSCAPE model are sensitive to the pollen productivity estimates used, the regional background pollen loading and average wind speed. There is a difference in background pollen loading between eastern and western Denmark, especially of Calluna pollen. The fit between predicted and observed pollen assemblages is best at wind speeds around 2.5 m s−1, and decreases rapidly at lower wind speeds. The pollen productivity estimates from the ad 1800 data set are comparable with estimates from moss polsters in modern analogues of traditional cultural landscapes in Sweden and Norway.

Main conclusions  The POLLSCAPE model reproduces the patterns in the observed pollen assemblages from the lakes well, considering the uncertainty in the historical plant abundance data. This study indicates that the simulation model can be a useful tool for investigating relationships between vegetation and pollen composition, but also that the simulated pollen proportions are sensitive to the pollen productivity estimates, the regional background and to wind speed.
Validation of a clinical guideline on prevention of venous thromboembolism in medical inpatients: a before‐and‐after study with systematic ultrasound examination
Authors: Labarere J. , Bosson J.‐L. , Brion J.‐P. , Fabre M. , Imbert B. , Carpentier P. , Pernod G.
Published: September 2004

Background.  Clinical practice guidelines on prevention of venous thromboembolism in medical inpatients have been implemented in various settings, although few studies have assessed their impact on venous thromboembolism events.

Objective.  To determine whether the implementation of a locally developed guideline is followed by changes in the rate of deep vein thrombosis.

Design.  A before‐and‐after study consisting in two ‘1‐day’ cross‐sectional studies.

Setting.  Thirteen adult medical wards in a teaching hospital in France.

Subjects.  All the patients hospitalized on the day of the cross‐sectional study.

Intervention.  A clinical guideline integrating scientific evidence and data on target medical providers’ practices was developed by a local expert panel and implemented through a multifaceted intervention.

Measurements.  Prevalence of deep vein thrombosis detected by systematic ultrasound examination.

Results.  The study included 338 patients in the preintervention sample and 340 in the postintervention sample. The prevalence of deep vein thrombosis decreased from 9.5% (95% CI, 6.6–13.1) in the preintervention sample to 3.2% (95% CI, 1.6–5.7) in the postintervention sample (P < 0.01). The decrease in the rate of thrombosis involved all deep veins of the lower limbs and remained significant after adjustment for risk factors (adjusted odds ratio = 0.47, 95% CI, 0.32–0.70). No additional cases of pulmonary embolism or deep vein thrombosis were reported either on the day of the study or in the following 2 days.

Conclusions.  Active implementation of a clinical practice guideline directed at medical providers (doctors, nurses and physical therapists) can be followed by a significant decrease in prevalence of deep vein thrombosis.
Risk of coronary events by baseline factors during 28 years follow‐up and three periods in a random population sample of men
Authors: Wilhelmsen L. , Lappas G. , Rosengren A.
Published: September 2004

Aims. To investigate the predictive value of risk factors for coronary events measured in midlife during three separate periods over a follow‐up period extending through 28 years.

Methods. A total of 7437 men aged 47–55 years and free of myocardial infarction at baseline were examined. Risk of coronary events (nonfatal myocardial infarction and coronary deaths) was analysed for the entire period and for 0–15, 16–21 and 22–28 years’ follow‐up, using age‐adjusted and multiple Cox regression analyses.

Results. Age, diabetes, elevated blood pressure and serum cholesterol were all independently associated with increased risk of coronary events for the entire 28 years as well as for each of the periods. A family history of coronary events amongst fathers, mothers and siblings was independently significant for the entire follow‐up period, and the risk did not decline with extended follow‐up. Effort‐related chest pain was a strong and independent risk factor for the first 21 years but not thereafter. The importance of smoking decreased over time and was not significantly associated with outcome during the last period. Stress was also significant for the entire 28 years, but in selected periods only up to 21 years. Body mass index, low physical activity and low social class were inconsistently or not at all related to outcome in multiple analyses.
The use of lamivudine for patients with acute hepatitis B (a series of cases)
Authors: Kondili L. A. , Osman H. , Mutimer D.
Published: September 2004

Summary.  There are limited data on the use of lamivudine for patients with severe forms of acute hepatitis B. We report our experience with the use of lamivudine in six patients with acute HBV infection. Lamivudine was justified by disease severity for four patients and by concerns about risk of chronicity for two patients. The diagnoses of the treated patients were: fulminant liver failure (two patients), severe acute hepatitis B, protracted acute hepatitis B, and new HBV infection in the renal dialysis setting (two patients, one with severe liver injury). Serum HBV DNA titres ranged from 105 to 107 copies/mL prior to commencement of lamivudine. Lamivudine treatment was associated with a decline in serum HBV DNA and serum transaminases in all patients. All but one patient survived. A 58‐year‐old man with fulminant hepatitis and multiple organ failure died despite antiviral treatment. When possible, HBeAg and HBsAg seroconversion was documented during follow‐up. In the absence of a randomized, prospective study of lamivudine in patients with severe acute hepatitis B, our data encourage the use of this safe and well tolerated drug.
Racial differences in responses to interferon‐β‐1a in chronic hepatitis C unresponsive to interferon‐α: a better response in Chinese patients
Authors: Cheng P.‐N. , Marcellin P. , Bacon B. , Farrell G. , Parsons I. , Wee T. , Chang T.‐T.
Published: September 2004

Summary.  Re‐treatment with interferon‐α alone for chronic hepatitis C nonresponders to interferon‐α monotherapy is almost ineffective. This multicentre, randomized, parallel‐group, dose‐finding study evaluated the efficacy of interferon‐β‐1a in the treatment of chronic hepatitis C patients unresponsive to interferon‐α. A total of 267 patients were randomized to one of four groups: subcutaneous interferon‐β‐1a 12 MIU (44 μg) or 24 MIU (88 μg) administered three times weekly or daily. Patients were treated for 48 weeks and then followed up for an additional 24 weeks. There was a trend towards a dose–response relationship regarding virological [loss of detectable serum hepatitis C virus (HCV) RNA] and biochemical response (normalization of serum alanine aminotransferase). Overall, 22 patients (8.3%) had a virological response at the end of treatment; nine patients (3.4%) had a sustained virological response (SVR). Strikingly, 21.7% (5/23) of Chinese patients achieved SVR. Univariate analysis revealed that race was the only variable related to SVR [odds ratio (OR) 16.6; 95% CI 4.1–67.3; P < 0.0001]. Multiple logistic regression analysis also confirmed that more Chinese patients achieved SVR than non‐Chinese patients (OR 12.3; 95% CI 2.6–59.3; P = 0.0017). In addition, complete clearance of HCV‐RNA occurred earlier in Chinese than in non‐Chinese responders (median 2 vs 30 weeks; P = 0.020). Thirty‐six patients were withdrawn from treatment because of adverse events. Most adverse events were mild or moderate in severity. In conclusion, interferon‐β‐1a provided considerable clinical benefit in Chinese patients with chronic hepatitis C unresponsive to interferon‐α. The evaluation of interferon‐β‐1a in this setting is progressing.
Hepatocellular carcinoma: role of hepatitis B and hepatitis C viruses proteins in hepatocarcinogenesis
Authors: Anzola M.
Published: September 2004

Summary. Hepatocellular carcinoma (HCC) is the most important primary hepatic cancer, being a common cancer type worldwide. Many aetiological factors have been related with HCC development, such as cirrhosis, hepatitis viruses and alcohol. Chronic infection with hepatitis B (HBV) and C viruses (HCV) often results in cirrhosis and enhances the probability of developing HCC. The underlying mechanisms that lead to malignant transformation of infected cells, however, remain unclear. HBV is a DNA virus that integrates into the host genome, and this integration is believed, in part, to be carcinogenic. Besides, the virus encodes a 17 kDa protein, HBx, which is known to be a causative agent in the formation of HCC. On the contrary, HCV is a RNA virus that does not integrate into the host genome but likely induces HCC through host protein interactions or via the inflammatory response to the virus. Products encoded in the HCV genome interfere with and disturb intracellular signal transduction. Some HCV proteins, such as the core protein, NS3 and NS5A, have seen to have a regulatory effect on cellular promoters, to interact with a number of cellular proteins, and to be involved in programmed‐cell death modulation under certain conditions. The identification of these proteins functions in HCC development and the subsequent development of strategies to inhibit protein–protein interactions may be the first step towards reducing the chronicity and/or of the carcinogenicity of these two viruses.
Kinetics of hepatitis B viral load during 48 weeks of treatment with 600 mg vs 100 mg of lamivudine daily*
Authors: Wang C. C. , Holte S. , Huang M.‐L. , Sacks S. L. , Engelberg R. , Ferrenberg J. , Shuhart M. , Corey L.
Published: September 2004

Summary.  Oral therapy for chronic hepatitis B remains suboptimal. Mathematical modelling of viral decay kinetics to rapidly assess potential antiviral regimens has proved valuable for human immunodeficiency virus and cytomegalovirus. We defined the kinetics of viral replication in 10 chronic hepatitis B patients randomized to lamivudine 100 mg vs 600 mg for 48 weeks. Viral decay kinetics conformed to a biphasic pattern in nine of 10 subjects. Persons receiving 600 mg daily of lamivudine exhibited a 1.6‐fold faster decay rate in the infected cell compartment (0.028/day vs 0.017/day, P = 0.06) and a greater overall change in serum viral load when compared with those receiving 100 mg (4.06 vs 1.52 log10 copies/mL, P = 0.08). More potent therapy appeared to result in more rapid decrease in the infected cell population. Studies using mathematical modelling of viral decay may be a useful method to evaluate single or combination therapy for HBV infection in vivo.
Effects of ribavirin combined with interferon‐α2b on viral kinetics during first 12 weeks of treatment in patients with hepatitis C virus genotype 1 and high baseline viral loads
Authors: Enomoto M. , Nishiguchi S. , Kohmoto M. , Tamori A. , Habu D. , Takeda T. , Seki S. , Shiomi S.
Published: September 2004

Summary.  This study aimed to find how ribavirin increases viral disappearance in patients with hepatitis C virus (HCV) of genotype 1 and high baseline viral loads (>5.0 ×105 copies/mL) when given with interferon (IFN). Using the real‐time quantitative polymerase chain reaction, we measured serum HCV in 20 patients during the first 12 weeks of therapy with IFN‐α2b and ribavirin. Controls were 10 similar patients given IFN‐α2b alone. IFN‐α2b was given at 6 MU daily for 2 weeks, and then three times weekly. Ribavirin was given at 600 or 800 mg daily. Serum HCV RNA decreased rapidly in the first phase, during the first 24 h of therapy (day 0), and more slowly in the early second phase (days 1–14). The median decrease was by 1.41 and 0.078 log 10/day in these two phases in the combination therapy group, and 0.90 and 0.081 log 10/day in the monotherapy group. The difference between groups in the first phase was not significant (P = 0.24), nor was that in the next phase (P = 0.68). Later in the second phase, between days 14 and 84, the median decrease was larger in the combination therapy group (0.030 log 10/day) than in the monotherapy group (0.015 log 10/day, P = 0.035). In patients with HCV genotype 1 and high viral loads, the effects of ribavirin with IFN‐α appeared slowly, after the earliest days of treatment. A long‐term favourable outcome of combination therapy may be associated with a rapid viral decline in this later phase of therapy.
Introduction of NS5A mutations enables subgenomic HCV replicon derived from chimpanzee‐infectious HC‐J4 isolate to replicate efficiently in Huh‐7 cells
Authors: Maekawa S. , Enomoto N. , Sakamoto N. , Kurosaki M. , Ueda E. , Kohashi T. , Watanabe H. , Chen C.‐H. , Yamashiro T. , Tanabe Y. , Kanazawa N. , Nakagawa M. , Sato C. , Watanabe M.
Published: September 2004

Summary.  Hepatitis C virus (HCV) subgenomic replicon has been reported to replicate efficiently and continuously in human hepatoma Huh‐7 cells. To extend the previous results to other isolated HCV clones, we constructed another HCV replicon from HC‐J4, one of chimpanzee‐infectious HCV clones. An HCV replicon derived from HC‐J4 (RpJ4) consists of HCV‐5′ untranslated region, neomycin phosphotransferase gene, the encephalomyocarditis virus internal ribosomal entry site, HCV nonstructural region, NS3 to NS5B, and HCV‐3′ untranslated region. The adaptive mutations known to be required for HCV‐Con1 replicon were introduced in RpJ4 replicon, aa.(amino acids number according to HC‐J4) 2197 serine to proline, deletion of serine at aa.2201, and aa.2204 serine to isoleucine (RpJ4‐S2197P, RpJ4‐S22001del, and RpJ4‐S2204I). RpJ4/ISDR mutant and RpJ4‐S2201del/ISDR mutant were also constructed by introducing six amino acid mutations into the interferon sensitivity determining region (ISDR). After transfection into Huh‐7 cells and G418 selection, RpJ4 and RpJ4/ISDR mutants did not produce any colony. In contrast, G418‐resistant cells were transduced efficiently by RpJ4‐S2197P, RpJ4‐S2204I, RpJ4‐S2201del and RpJ4‐S2201del/ISDR mutant, with the RpJ4‐S2201del/ISDR mutant being most efficient. Hence the HCV replicon derived from HC‐J4 can replicate efficiently following the introduction of adaptive mutations into the upstream region of ISDR. Moreover, additional introduction of mutations into ISDR further enhanced its replication. These findings demonstrate that the genetic structure of the NS5A domain is critical in HCV replications.