bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of glycine responses by dihydropyridines and verapamil in rat spinal neurons
Authors: Chesnoy‐Marchais Dominique , Cathala Laurence
Published: March 2003

Although glycine receptors (GlyRs) are responsible for the main spinal inhibitory responses in adult vertebrates, in the embryo they have been reported to mediate depolarizing responses, which can sometimes activate dihydropyridine‐sensitive l‐type calcium channels. However, these channels are not the only targets of dihydropyridines (DHPs), and we questioned whether GlyRs might be directly modulated by DHPs. By whole‐cell recording of cultured spinal neurons, we investigated modulation of glycine responses by the calcium channel antagonists, nifedipine, nitrendipine, nicardipine and (R)‐Bay K 8644, and by the calcium channel, agonist (S)‐Bay K 8644. At concentrations between 1 and 10 µm, all these DHPs could block glycine responses, even in the absence of extracellular Ca2+. The block was stronger at higher glycine concentrations, and increased with time during each glycine application. Nicardipine blocked GABAA responses from the same neurons in a similar manner. In addition to their blocking effects, nitrendipine and nicardipine potentiated the peak responses to low glycine concentrations. Both effects of extracellular nitrendipine on glycine responses persisted when the drug was present in the intracellular solution. Thus, these modulations are related neither to calcium channel modulation nor to possible intracellular effects of DHPs. Another type of calcium antagonist, verapamil (10–50 µm), also blocked glycine responses. Our results suggest that some of the effects of calcium antagonists, including the neuroprotective and anticonvulsant effects of DHPs, might result partly from their interactions with ligand‐gated chloride channels.
Further polymorphism of the MICA gene
Authors: Pérez‐Rodríguez M. , Argüello J. R. , Fischer G. , Corell A. , Cox S. T. , Robinson J. , Hossain E. , McWhinnie A. , Travers P. J. , Marsh S. G. E. , Madrigal J. A.
Published: March 2003

The MHC class I chain‐related (MIC) gene family constitutes an interesting genetic group that is related to major histocompatibility complex (MHC) class I genes and is located within the MHC. The MIC gene products, MICA and MICB, have similar structures to HLA class I molecules. So far over 50 MICA alleles have been reported, which suggests that this genetic system is highly polymorphic. In order to investigate further the extent of MICA polymorphism we have studied exons 2–5 of the MICA gene in over 200 homozygous and heterozygous cell lines. Altogether we have identified 11 new MICA alleles and report 13 new nucleotide variations, one in exon 2, four in exon 3, four in exon 4, two in intron 1, one in intron 4 and one (a deletion) in exon 4. Eight of the 10 exonic variations are non‐synonymous. The deletion in exon 4 leads to a frame‐shift mutation and the introduction of a repeat of 12 leucine residues encoded by the microsatellite in exon 5. This study provides further evidence that the MICA gene is highly polymorphic. In contrast to MHC class I molecules, the polymorphic sites in MICA are predominantly within the α2and α3domains. The distribution of synonymous and non‐synonymous substitutions suggests that there is selection for the polymorphic positions, which therefore define potential functional sites in the protein. We were also able to determine the association between MICA and HLA‐B alleles in a number of homozygous cell lines bearing extended haplotypes.
Cell volume and rate of proliferation, but not protein expression pattern, distinguish pup/intimal smooth muscle cells from subcultured adult smooth muscle cells
Authors: McKilligin E. , Grainger D. J.
Published: March 2003

Smooth muscle cells from neonatal rats and from injured blood vessels grow with a characteristic cobblestone morphology that distinguishes them from adult smooth muscle cells. This has led to the proposition that there are two distinct types of smooth muscle cells with different proliferative capacity. Here we systematically compare the properties of subcultured adult smooth muscle cells in culture and clonal lines of cobblestone smooth muscle cells from both neonatal rats and injured vessels. The cobblestone smooth muscle cells have a significantly smaller average cell volume, estimated using two different flow cytometry measurements. However, the two types of smooth muscle cells have indistinguishable protein expression patterns when the levels of more than 20 different proteins (including cytoskeletal proteins, matrix proteins, cytokines, cytokine receptors, adhesion molecules and enzymes) are measured by quantitative immunofluorescence. Furthermore, in contrast to previous observations, we demonstrate that both types of smooth muscle cells secrete a powerful mitogenic activity. The higher cell density achieved by the cobblestone smooth muscle cells in culture was responsible for the earlier reports that this mitogenic activity was secreted only by cobblestone smooth muscle cells. We conclude that many of the differences seen between cobblestone smooth muscle cells and adult smooth muscle cells in vitro (proliferation rate, morphology, protein expression pattern, secretion of mitogenic activity) could be attributable to a stable difference in the median cell volume of the cultures.
Delayed ultrasound in patients with abdominal pain and vaginal bleeding during the first trimester of pregnancy
Authors: Hendry James N , Naidoo Yuresh
Published: March 2003

Objectives:

To determine if patients with abdominal pain and vaginal bleeding during the first trimester of pregnancy who have a low clinical likelihood of ectopic pregnancy are put at risk of adverse events by delaying ultrasonography 12–18 h after emergency department presentation.

Methods:

A retrospective chart review of all surgically proven ectopic pregnancies at our Institution over a 2‐year period.

Results:

One hundred and seventeen cases of ectopic pregnancy were reviewed. Thirty‐seven cases met predetermined criteria of ‘clinical stability’ at first presentation. These patients waited a median 14 h for diagnostic ultrasound with 62% waiting more than 12 h. No adverse events occurred while waiting for this diagnostic study.

Conclusions:

Preliminary results suggest that pregnant patients with abdominal pain and vaginal bleeding in the first trimester who meet specific low‐risk clinical criteria could potentially have ultrasound delayed 12–18 h without risk of adverse event. Further prospective studies are warranted to confirm the safety of this strategy.
Weathering the storm: Beta‐blockade and the potential for disaster in severe hyperthyroidism
Authors: Fraser Todd , Green David
Published: March 2003

Some patients with advanced thyrotoxicosis have occult cardiac dysfunction. The use of long‐acting beta‐blockers, traditional in the management of thyrotoxicosis, may have disastrous consequences in this setting. The following report documents the cardiovascular collapse and asystolic arrest of a patient with hyperthyroidism when treated with sotolol. Though the patient was successfully resuscitated, the long duration of action of sotolol necessitated prolonged inotropic and vasopressor support. A shorter acting beta‐blocker, such as esmolol, theoretically may be a safer option.
Abstract to publication ratio for papers presented at scientific meetings: How does emergency medicine compare?
Authors: Walby Andrew , Kelly Anne‐Maree , Georgakas Con
Published: March 2003

Objectives:

The aims of the present study were to determine the publication rate of abstracts presented by Australasian emergency physicians at major emergency medicine meetings and to identify the site of publication of papers.

Method:

All free paper abstracts presented (oral and poster) by Australasian emergency physicians and trainees at five Australasian College for Emergency Medicine/Australasian Society for Emergency Medicine and International Conference on Emergency Medicine meetings between 1995 and 1998 were identified retrospectively from conference programmes. In order to determine whether or not the abstract had been published, the PubMed database (http://www4.ncbi.nlm.nih.gov/PubMed/) was searched using the presenter’s name and key words from the abstract. In addition, a hand search of the non‐abstracted journal Emergency Medicine was conducted.

Results:

Of the 207 free paper abstracts identified, 73 (35%) had been published as full articles. Papers were published in a variety of journals; however, Emergency Medicine accounted for almost half the published papers. The mean time between presentation and publication was 12.6 months (median 11 months).

Conclusion:

The abstract to publication rate for papers presented by Australasian emergency physicians and trainees at Australasian College for Emergency Medicine/Australasian Society for Emergency Medicine and International Conference on Emergency Medicine meetings is 35%, which is lower than that reported by some other established specialities, but comparable to rates reported for US‐based national and international emergency medicine meetings. Future research should look at barriers to the publication of findings and ways to assist the publication process. See Commentary, page 407.
USE OF MEDICARE SERVICES RELATED TO DIABETES CARE: THE IMPACT OF RURAL ISOLATION
Authors: Overland Jane , Yue Dennis K. , Mira Michael
Published: March 2003

This study used Medicare data for people living in New South Wales (NSW) (1993–1997) to examine the impact of rural isolation on the utilisation of diabetes health care services. The relative odds of attending a specialist was slightly higher for people in urban areas when compared to their rural counterparts but reached as high as 1.85 in regard to attendance to consultant physicians. Surveillance of diabetes parameters over the 5 year period showed greatest improvement in rural areas. The proportion of patients each year with glycaemic control assessed by quantification of glycosylated haemoglobin (HbA1c) or renal function and vascular risk by microalbuminuria estimation rose to 57.4% and 12.3%, respectively, in rural areas compared to 55.2% and 11.3% in major urban areas. This study has shown that the level of monitoring in rural areas is equal to urban areas, despite decreased access to medical care, highlighting the vital role GPs play in diabetes management in rural NSW.
Two‐thirds of Atrophic Body Gastritis Patients Have Evidence of Helicobacter pylori Infection
Authors: Annibale Bruno , Negrini Riccardo , Caruana Pietro , Lahner Edith , Grossi Cristina , Bordi Cesare , Fave Gianfranco Delle
Published: March 2003

Background.

Helicobacter pylori is involved in the induction of atrophic body gastritis (ABG). During the progression of atrophic gastritis the disappearance of H. pylori has been documented and in time serology is the only sign that indicates a previous infection. It has been shown that a positive serology, in ABG patients without histological evidence of infection, indicates an active H. pylori infection.

Aim.

To investigate in a population of patients with ABG the prevalence of H. pylori infection on the basis of histology and serology.

Patients.

A total of 150 consecutive outpatients with atrophic body gastritis were diagnosed on the basis of a screening system.

Methods.

All patients had a detailed assessment including measurement of specific anti‐H. pylori antibodies, parietal cell antibodies, and fasting gastrin, gastroscopy with biopsies from gastric antrum and body.

Results.

24.6% of patients were histologically and serologically negative (Group A). 52.7%H. pylori was not detected on histology but IgG to H. pylori were in all these patients elevated (Group B). 22.6% of patients were found to be positive at histology in the corpus mucosa; all but one of these patients had elevated circulating IgG to H. pylori (Group C). Mean corporal atrophy score in Group B patients was statistically lower than in Group A patients (2.43 ± 0.08 vs. 2.75 ± 0.09; p < .05), but was statistically higher than in Group C patients (1.79 ± 0.11; p < .001). Thus, in corporal mucosa a gradient of atrophy was shown: Group C < Group B < Group A. A similar gradient was observed for the presence of pernicious anemia being lowest in Group C 11.8% increasing to 45.6% in Group B and being highest in Group C 75.6%. A statistical correlation was obtained (r = .04791, p < .05) between the histological score of corporal atrophy and the titer of antibodies to parietal cells and an inverse correlation was obtained (r = − .2322, p < .0001) between the histological score of corporal atrophy and IgG to H. pylori.

Conclusion.

This study shows that two‐thirds of ABG patients have evidence of H. pylori infection. This suggests that atrophic gastritis of the corpus is a spectrum of damage where H. pylori is a key agent able to induce gastric atrophic damage and also gastric autoimmunity.
Cardiovascular Risk Factors in Subjects with Helicobacter pylori Infection
Authors: Takashima Toshiharu , Adachi Kyoichi , Kawamura Akira , Yuki Mika , Fujishiro Hirofumi , Rumi Mohammad Azharul Karim , Ishihara Shunji , Watanabe Makoto , Kinoshita Yoshikazu
Published: March 2003

Background. It has been proposed that Helicobacter pylori infection is related to cardiovascular disease, although this has not been fully investigated. The aim of this study was to investigate whether H. pylori in‐fection is associated with cardiovascular risk factors.

Subjects and Methods. One thousand six hundred and fifty people undergoing annual medical checks at Shimane Institute of Health Science between September 1998 and August 1999 were enrolled. Gender, age, body mass index, habitual smoking and drinking, systolic and diastolic blood pressure, serum level of total cholesterol, triglyceride, high‐density lipoprotein cholesterol (HDLC), blood glucose, leukocyte count and hemoglobin were compared between H. pylori seropositive and seronegative cases.

Results. In H. pylori seropositive individuals, HDLC was significantly lower than that in seronegative individuals. After adjustment for possible confounding factors (gender, age, BMI, smoking and drinking habits), mean HDLC in H. pylori‐seropositive and seronegative individuals were 56.1 and 58.2 mg/dl, respectively (p < .005). The percentage of the elderly (over 50 years old) individuals with HDLC < 35 mg/dl in H. pylori seropositive and seronegative groups were 7.4% and 4.7%, respectively (p < .001). In addition, the lower HDLC level was accompanied by an increased leukocyte count.

Conclusion. Long‐term infection with H. pylori may have an important role in decreasing the serum HDLC concentration.
Removal of Mucus for Ultrastructural Observation of the Surface of Human Gastric Epithelium Using Pronase
Authors: Saito Nagahito , Sato Fujio , Oda Atsushi , Kato Mototsugu , Takeda Hiroshi , Sugiyama Toshiro , Asaka Masahiro
Published: March 2003

Background. Helicobacter pylori adhering to the human gastric epithelium causes gastric diseases such as ulcer, carcinoma and lymphoma. It is thus important to observe in detail both the surface of the epithelial cells and the H. pylori that adhered to it for the elucidation of H. pylori‐induced diseases by scanning electron microscopy (SEM). Since the thick mucus layer blocks the observation of the cell surface and the bacteria, it is generally eliminated during the processing for SEM by roughly mechanical methods, but these treatments also demolish the ultrastructure of the cells. We studied the nonmechanical method for removal of mucus layer of gastric epithelium using pronase.

Materials and Methods. To determine the optimal concentration of pronase, mucin was used as a substrate for inhibition of the viscosity. Pronase was added in 2% mucin at the concentration of 10, 50, 100, 500, 1000, 2000 or 5000 unit/ml and the flowing time of the mixture was measured. Based on the digestion experiment, biopsied specimens from 24 patients with dyspepsic symptoms were fixed in glutaraldehyde and then washed in rolling with different concentration of pronase. After the pretreatment by pronase, the specimens were treated according to the standard process for SEM.

Results. We succeeded in removing the mucus layer on the surface of epithelial cells from the biopsied specimens fixed in glutaraldehyde by rinsing with 2000 unit/ml pronase for 24 hours.

Conclusions. Using our digestive method without destroying the ultrastructure, the earliest stage which H. pylori has adhered onto the human gastric epithelium can be observed for the investigation of H. pylori‐induced gastric disorders by SEM.
Functional study of the central nervous system for farm animal husbandry
Authors: SAITO Toshiyuki
Published: March 2003

The purpose of this mini‐review is to describe the recent approaches for revealing the function of the central nervous system in farm animals. The sensory organs are the first sites to gain environmental information. The behavior of the animals is outputted as a result of changes in the integrated neuronal systems, and is largely influenced by the external environment. Therefore, it is necessary to know how farm animals catch and recognize environmental changes. To understand the mechanisms of sensing and behavioral output, approaches for analyzing the brain function are required. Neuroscientific approaches are able to give cues for resolving abnormal behaviors such as stereotypy, and may lead to the improved housing and management of farm animals.
Reduction of urinary nitrogen excretion and ammonia emission from slurry by feeding a low protein diet supplemented with apple pomace to growing pigs
Authors: YAMAMOTO Akemi , ITOH Minoru , KADOYA Yoshikatsu , KANNO Hirokazu , YAMADA Michi , FURUYA Shu
Published: March 2003

An experiment was conducted to determine the effects of supplementing a reduced crude protein (CP) diet with apple pomace on the urinary nitrogen excretion and ammonia emission from slurry in the growing pigs. Four barrows (35 kg bodyweight) were assigned to one of two diets. Each pig was placed in a metabolism cage and fed a low CP, amino acid‐supplemented diet (CP 11.33%; low CP diet) or a low CP, amino acid‐supplemented diet containing 23.08% dried apple pomace (CP 9.47%; apple pomace diet) for two 14‐day experimental periods. After the completion of the first period, the pigs were switched to the other diet. Urine and feces were quantitatively collected daily for 5 days after a 9‐day adaptation period. The daily nitrogen intake for the low CP diet and the apple pomace diet was 17.76 g/pig and 18.64 g/pig, respectively. The pigs fed the apple pomace diet excreted more fecal nitrogen (6.86 g/day) than the pigs fed the low CP diet (3.63 g/day) (P < 0.001), but urinary nitrogen excretion with the apple pomace diet was 3.11 g/day, which was much lower than that for the low CP diet (5.95 g/day) (P < 0.001). The daily ammonia emission from the mixture of urine and feces determined by an in vitro method was much lower for pigs fed the apple pomace diet (120 mg) than that for pigs fed the low CP diet (603 mg) (P < 0.01). The addition of apple pomace to a reduced CP, amino acid‐supplemented diet reduces urinary nitrogen excretion and thereby ammonia emission.
Nuclear transfer using a bovine mammary epithelial cell line (BMEC)
Authors: AKAGI Satoshi , TAKAHASHI Seiya , OHKOSHI Katsuhiro , TAKENOUCHI Takato , SHIMIZU Manabu , GESHI Masaya , ADACHI Noritaka , FUCHIMOTO Dai‐ichiro , IZAIKE Yoshiaki , ASO Hisashi
Published: March 2003

The developmental potential of nuclei from a bovine mammary epithelial cell line (BMEC) in nuclear transfer was investigated. For nuclear transfer donors, BMEC cells (passage 15) were cultured for 4–5 days after seeding at cell densities of 1.0 × 105 cells/cm2 (high‐density group) or 0.8 × 104 cells/cm2 (low‐density group). First, the effective electric stimulation for fusion of enucleated oocytes with BMEC cells was examined. Fusion rates reached maximum with two DC pulses of 30 V/150 µm for 20 µs in the high‐density group and with two DC pulses of 25 V/150 µm for 10 µs in the low‐density group. The fusion rate (37.5%) in the high‐density group was significantly (P < 0.005) lower than in the low‐density group (71.4%). Second, the in vitro developmental potential of nuclear transfer embryos derived from BMEC cells was examined. In the high‐density and low‐density groups, 18.8% and 24.1% of fused oocytes, respectively, developed to blastocyst stage. The results of this study indicate that nuclei from BMEC cells support the development of nuclear transfer embryos to the blastocyst stage and that the efficiency of oocyte–cell fusion is affected by the culture conditions of the donor BEMC cells before nuclear transfer.
Quantitative studies of the in vitro production of pipecolic acid by rumen protozoa and its degradation by rumen bacteria
Authors: HUSSAIN‐YUSUF Hazizul , ONODERA Ryoji , NASSER Mohamed Emad A. , SULTANA Halima , SATO Hiroyuki
Published: March 2003

An in vitro study was conducted to quantitatively investigate the metabolism of pipecolic acid (Pip), a neuromodulator, by mixed rumen bacteria (B), mixed rumen protozoa (P), a combination of B and P (BP), species‐enriched rumen protozoal suspension (Polyplastron sp., Diploplastron sp., entodinia and Entodinium caudatum) and pure cultures of several isolates of rumen bacteria (Prevetolla bryantii, Prevetolla albensis, Streptococcus bovis, Veillonella parvula, Megasphaera elsdenii and Ruminococcus albus). Only P produced Pip from L‐lysine (1.0 mmol/L L‐Lys) at a rate of 83.5 ± 1.6 µmol/L/h and even in BP, Pip was produced from L‐Lys by P and increased at a rate of 31.2 ± 3.8 µmol/L/h. Pip production by P was highest when the substrate (L‐Lys) concentration was 6 mmol/L and then the rate was 580 ± 36 µmol/L/h. Pipecolic acid production by P suspension enriched with different species of protozoa showed that Polyplastron sp. had the highest Pip production rate of 0.907 ± 0.092 µmol/L/mg protozoal protein per h, and Diploplastron sp. had the lowest rate of 0.55 ± 0.13 µmol/L/mg protozoal protein per h. The addition of D‐Lys (1.0 mmol/L) as a substrate to the P suspension revealed that P were also able to produce Pip from D‐Lys, though at a lower rate (1/3) compared with L‐Lys (1.0 mmol/L), suggesting the presence of epimerases in P. It was confirmed that B were unable to produce Pip from L‐ or D‐Lys. Only B degraded Pip (1.0 mmol/L) after a lag phase at a rate of 56.0 ± 1.5 µmol/L/h. The B suspension was able to degrade D‐Lys, though the products were not identified. Pip degradation by pure culture of some species of rumen bacteria showed that P. bryantii and R. albus had the highest rate followed by P. albensis, S. bovis and M. elsdenii with a low rate of Pip degradation. Veillonella parvula showed no ability to degrade Pip. The results suggest that a fairly large proportion of rumen‐produced Pip is likely to be absorbed by the host animal before degradation by rumen bacteria.
Heterologous expression of gassericin A, a bacteriocin produced by Lactobacillus gasseri LA39
Authors: KAWAI Yasushi , ARAKAWA Kensuke , ITOH Ayako , SAITOH Boku , ISHII Yasuyuki , NISHIMURA Junko , KITAZAWA Haruki , ITOH Takatoshi , SAITO Tadao
Published: March 2003

Gassericin A, a bacteriocin produced by Lactobacillus gasseri LA39, has a cyclic structure linking N‐ and C‐terminal amino acids. Gassericin A was expressed in Escherichia coli JM109 as a biotinylated fusion protein on the basis of the DNA sequence of mature bacteriocin. A positive clone accumulated the bacteriocin, with no activity, as a soluble fusion protein in the cytoplasm. After release of an N‐terminal tag with factor Xa protease, gassericin A was converted into an active peptide having N‐ and C‐termini. The total amount of purified bacteriocins (expressed and native) was 480 µg/L and 370 µg/L, respectively. However, the specific activity of expressed gassericin A was 15 AU/mg lower than that of native bacteriocin (2600 AU/mg). Although the actual Mr (molecular weight) of the expressed bacteriocin should be 5666, the peptide showed the same mobility (Mr 3800) in sodium dodecylsulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) as native cyclic gassericin A, suggesting that the expressed peptide retains compact folding of the molecule similar to that of native gassericin A.
Results of an orthopaedic survey in young patients with severe haemophilia in Spain
Authors: Tusell J. M. , Aznar J. A. , Querol F. , Quintana M. , Moreno M. , Gorina E. ,   THE ORTHOPAEDIC STUDY GROUP
Published: March 2003

Summary.  This paper outlines the results obtained in a cross‐sectional study of a group of young patients with severe haemophilia A and B. The primary aim of the study was to ascertain the level of orthopaedic complications in the group, the effects that these complications have on quality of life, and the medical resources used on these patients. The secondary aim was to relate their current orthopaedic state to the type of treatment received before the study. The study was carried out in 11 hospitals in Spain, where 70 severe haemophilia patients (factor VIII [FVIII] < 2%), with an average age of 21.6 and a median age of 22, and no inhibitors, were monitored. The percentage of patients suffering from articular complaints was 84.3% and 85.7% according to the Gilbert and Petterson scales, respectively. Furthermore, pain was reported in 16.1% of joints, most frequently in ankles. Using the SF‐36 Health Survey, patients were observed to have a poorer quality of life relative to healthy controls. Despite high levels of both the coagulant factor given to patients and the financial resources dedicated to their treatment, the type of treatment (on demand and/or as secondary prophylaxis) provided to the young adults was found to be incapable of preventing haemophilic arthropathy and subsequent negative quality of life consequences.
Effects of prophylactic treatment regimens in children with severe haemophilia: a comparison of different strategies
Authors: Van Den Berg H. M. , Fischer K. , Van Der Bom J. G. , Roosendaal G. , Mauser‐Bunschoten E. P.
Published: March 2003

Summary.  Both Sweden and the Netherlands have a long experience with primary prophylaxis in children with severe haemophilia. In these countries it has been offered to all children for the last 3–4 decades. In Sweden prophylaxis is generally started at an earlier age with a higher dosage and frequency than in the Netherlands. Patients in the Netherlands receive a more individually tailored regimen, with prophylaxis now started after the first one or two joint bleeds and dosages are increased when breakthrough bleeds occur. The current study evaluated the effect prophylaxis on long‐term outcomes and the consumption of clotting factor concentrates in Dutch and Swedish cohorts. Our results show that the orthopaedic outcome in the oldest groups of patients from Sweden and the Dutch cohorts were comparable, although the Swedish patients used twice as much clotting products per year. In the youngest patients, joint status is very good and further follow‐up is necessary to demonstrate the benefits of either strategy. In conclusion, more individually tailored regimens aimed at preventing bleeding prevent joint damage in children with severe haemophilia, while clotting factor consumption is about half of that in previously described regimens.
European data of a clinical trial with a sucrose formulated recombinant factor VIII in previously treated haemophilia A patients
Authors: Rothschild C. , Scharrer I. , Brackmann H.‐H. , Stieltjes N. , Vicariot M. , Torchet M.‐F. , Effenberger W.
Published: March 2003

Summary.  To increase the safety of antihaemophilic treatment, the production process of full‐length recombinant factor VIII (FVIII) KOGENATE® Bayer (Kogenate®FS)has been modified. Human albumin is no longer added as stabilizer during purification and in final formulation. Instead, the new KOGENATE® Bayer production process uses sucrose as a stabilizer in the formulation and adds solvent/detergent virus inactivation step. An European clinical trial was carried out in Germany and France in previously treated patients with severe haemophilia A who had more than 100 exposure days to exogenous FVIII. Pharmacokinetic data was analysed according to one‐stage and chromogenic assays. Efficacy and safety during home therapy and in surgical procedures were evaluated; inhibitor formation was carefully monitored. Safety and efficacy were evaluated in 33 European patients for 24 months. Patients received more than 13 million IU KOGENATE® Bayer. Over 75% of patients accrued more than 100 exposure days with the new product. Of 875 bleeding episodes, 90.7% were treated with 1 or 2 infusions and 75.8% of responses to treatment were rated as ‘excellent’ or ‘good’. Prophylactic treatment was the most common mode of therapy (60.7% of infusions). The product was well‐tolerated and FVIII recovery studies were consistent throughout the study period. Only 0.26% of adverse events were reported to be drug related. No evidence of de novo inhibitor formation was observed. Overall, KOGENATE® Bayer was efficacious, safe and well‐tolerated for the treatment of haemophilia A in multitransfused patients.
Experience with KOGENATE® Bayer in surgical procedures
Authors: Scharrer I. ,   THE KOGENATE Bayer Study Group
Published: March 2003

Summary.   The study objectives were to assess the efficacy of KOGENATE® Bayer (Kogenate® FS) in achieving haemostasis during surgical procedures in patients with severe haemophilia A and to evaluate its safety when given in the doses needed for this purpose. Dosing for surgical procedures was in accordance with clinical practice in the management of haemophilia A patients during and after surgery. Efficacy was evaluated by estimated blood loss and assessment of haemostasis as determined by the attending physician. Safety was assessed by the incidence of adverse events related to study drug and the incidence of viral seroconversions. In total, 15 previously treated patients (PTPs) and seven previously untreated patients (PUPs)/minimally treated patients (MTPs) underwent 30 surgical procedures ranging from minor (port placement/tooth extraction) to major (orthopaedic endoprosthesis/brain tumour excision) surgery. The efficacy profile was good to excellent as assessed by the attending physician, and recorded blood loss was minimal to none. No adverse events were recorded that were related to study drug. No viral seroconversions were observed. In conclusion, KOGENATE® Bayer was shown to be safe and efficacious in patients with severe haemophilia A during surgical procedures.
Carbon storage and fluxes in ponderosa pine forests at different developmental stages
Authors: Law B.E. , Thornton P.E. , Irvine J. , Anthoni P.M. , Van Tuyl S.
Published: March 2003

We compared carbon storage and fluxes in young and old ponderosa pine stands in Oregon, including plant and soil storage, net primary productivity, respiration fluxes, eddy flux estimates of net ecosystem exchange (NEE), and Biome‐BGC simulations of fluxes. The young forest (Y site) was previously an old‐growth ponderosa pine forest that had been clearcut in 1978, and the old forest (O site), which has never been logged, consists of two primary age classes (50 and 250 years old). Total ecosystem carbon content (vegetation, detritus and soil) of the O forest was about twice that of the Y site (21 vs. 10 kg C m−2ground), and significantly more of the total is stored in living vegetation at the O site (61% vs. 15%). Ecosystem respiration (Re) was higher at the O site (1014 vs. 835 g C m−2 year−1), and it was largely from soils at both sites (77% of Re). The biological data show that above‐ground net primary productivity (ANPP),NPPand net ecosystem production (NEP) were greater at the O site than the Y site. Monte Carlo estimates ofNEPshow that the young site is a source of CO2to the atmosphere, and is significantly lower thanNEP(O)byc. 100 g C m−2 year−1. Eddy covariance measurements also show that the O site was a stronger sink for CO2than the Y site. Across a 15‐km swath in the region,ANPPranged from 76 g C m−2 year−1at the Y site to 236 g C m−2 year−1(overall mean 158 ± 14 g C m−2 year−1). The lowestANPPvalues were for the youngest and oldest stands, but there was a large range ofANPPfor mature stands. Carbon, water and nitrogen cycle simulations with the Biome‐BGC model suggest that disturbance type and frequency, time since disturbance, age‐dependent changes in below‐ground allocation, and increasing atmospheric concentration of CO2all exert significant control on the net ecosystem exchange of carbon at the two sites. Model estimates of major carbon flux components agree with budget‐based observations to within ± 20%, with larger differences forNEPand for several storage terms. Simulations showed the period of regrowth required to replace carbon lost during and after a stand‐replacing fire (O) or a clearcut (Y) to be between 50 and 100 years. In both cases, simulations showed a shift from net carbon source to net sink (on an annual basis) 10–20 years after disturbance. These results suggest that the net ecosystem production of young stands may be low because heterotrophic respiration, particularly from soils, is higher than the NPP of the regrowth. The amount of carbon stored in long‐term pools (biomass and soils) in addition to short‐term fluxes has important implications for management of forests in the Pacific North‐west for carbon sequestration.
Monoterpene emission and monoterpene synthase activities in the Mediterranean evergreen oak Quercus ilex L. grown at elevated CO2 concentrations
Authors: Loreto Francesco , Fischbach Robert J. , Schnitzler Jörg‐Peter , Ciccioli Paolo , Brancaleoni ENZO , Calfapietra Carlo , Seufert Guenther
Published: March 2003

Monoterpene emissions, monoterpene synthase activities, photosynthesis, fluorescence yield in the dark and drought stress indicators (stomatal conductance and mid‐day water potential) were concurrently measured under similar temperature and illumination in current‐year leaves of Quercus ilex L. of plants grown in open‐top chambers at ambient (350 ppm) and elevated (700 ppm) CO2. The study was undertaken to understand the effect of CO2 on monoterpene biosynthesis, and to predict and parameterize the biogenic emissions at growing CO2 concentrations. The results of the 1998 and 1999 studies show that at elevated CO2, and in the absence of persistent environmental stresses, photosynthesis was stimulated with respect to ambient CO2, but that the emission of the three most abundantly emitted monoterpenes (α‐pinene, sabinene and β‐pinene) was inhibited by approximately 68%. The enzyme activities of the monoterpene synthases catalysing the formation of the three monoterpenes were also inhibited at elevated CO2 and an excellent relationship was found between monoterpene emission and activity of the corresponding enzyme both at ambient and elevated CO2. Interestingly, however, limonene emission was enhanced in conditions of elevated CO2 as it was also the corresponding synthase. The ratio between enzyme activity and emission of the three main monoterpenes was high (above 20) at ambient CO2 but it was below 10 at elevated CO2 and, for limonene, on both treatments. Our results indicate that the overall emission of monoterpenes at elevated CO2 will be inhibited because of a concurrent, strong down‐regulation of monoterpene synthase activities. When the enzyme activity does not change, as for limonene, the high photosynthetic carbon availability at elevated CO2 conditions may even stimulate emission. The results of the 1997 study show that severe and persistent drought, as commonly occurs in the Mediterranean, may inhibit both photosynthesis and monoterpene (α‐pinene) emission, particularly at ambient CO2. Thus, emission is probably limited by photosynthetic carbon availability; the effect of elevated CO2per se is not apparent if drought, and perhaps other environmental stresses, are also present.
Modelling night‐time ecosystem respiration by a constrained source optimization method
Authors: Lai Chun‐Ta , Katul Gabriel , Butnor John , Ellsworth David , Oren Ram
Published: March 2003

One of the main challenges to quantifying ecosystem carbon budgets is properly quantifying the magnitude of night‐time ecosystem respiration. Inverse Lagrangian dispersion analysis provides a promising approach to addressing such a problem when measured mean CO2 concentration profiles and nocturnal velocity statistics are available. An inverse method, termed ‘Constrained Source Optimization’ or CSO, which couples a localized near‐field theory (LNF) of turbulent dispersion to respiratory sources, is developed to estimate seasonal and annual components of ecosystem respiration. A key advantage to the proposed method is that the effects of variable leaf area density on flow statistics are explicitly resolved via higher‐order closure principles. In CSO, the source distribution was computed after optimizing key physiological parameters to recover the measured mean concentration profile in a least‐square fashion. The proposed method was field‐tested using 1 year of 30‐min mean CO2 concentration and CO2 flux measurements collected within a 17‐year‐old (in 1999) even‐aged loblolly pine (Pinus taeda L.) stand in central North Carolina. Eddy‐covariance flux measurements conditioned on large friction velocity, leaf‐level porometry and forest‐floor respiration chamber measurements were used to assess the performance of the CSO model. The CSO approach produced reasonable estimates of ecosystem respiration, which permits estimation of ecosystem gross primary production when combined with daytime net ecosystem exchange (NEE) measurements. We employed the CSO approach in modelling annual respiration of above‐ground plant components (c. 214 g C m−2 year−1) and forest floor (c. 989 g C m−2 year−1) for estimating gross primary production (c. 1800 g C m−2 year−1) with a NEE of c. 605 g C m−2 year−1 for this pine forest ecosystem. We conclude that the CSO approach can utilise routine CO2 concentration profile measurements to corroborate forest carbon balance estimates from eddy‐covariance NEE and chamber‐based component flux measurements.
The effects of long‐term elevated UV‐B on the growth and phenolics of field‐grown silver birch (Betula pendula)
Authors: Tegelberg Riitta , Julkunen‐Tiitto Riitta , Aphalo Pedro J.
Published: March 2003

The effects of long‐term elevated UV‐B radiation on silver birch (Betula pendula Roth) seedlings were studied over three growing seasons in an outdoor experiment in Finland started 64 days after germination. One group of seedlings was exposed to a constant 50% increase in UV‐BCIE radiation, which corresponds to 20–25% of ozone depletion; another group received a small increase in UV‐A radiation and a third (the control group) received ambient solar radiation. Changes in growth appeared during the third growing season; the stems of the UV‐B treated seedlings were thinner and their height tended to be shorter compared with that of the control seedlings. In contrast, there were no UV‐B effects on biomass, bud burst, bud dry weights, leaf area, rust frequency index or chlorophyll concentrations in any of the summers. During the three‐year study, the flavonols were significantly increased by the elevated UV‐B only in the first growing season. The responses varied greatly among individual compounds; the most induced were the quercetin glycosides, while the main flavonols, myricetins, were reduced by the UV‐A control treatment. In the second summer phenolic acids, such as 3,4′‐dihydroxypropiophenone‐3‐glucoside, neochlorogenic acid and 5‐coumarylquinic acid, were increased by the UV‐B treatment. In the third year, the constitutive concentrations of phenolics were not affected by the UV‐B treatment.
The influence of elevated atmospheric CO2 on fine root dynamics in an intact temperate forest
Authors: Pritchard Seth G. , Rogers Hugo H. , Davis Micheal A. , Van Santen Edzard , Prior Stephen A. , Schlesinger William H.
Published: March 2003

Root dynamics are important for plant, ecosystem and global carbon cycling. Changes in root dynamics caused by rising atmospheric CO2 not only have the potential to moderate further CO2 increases, but will likely affect forest function. We used FACE (Free‐Air CO2 Enrichment) to expose three 30‐m diameter plots in a 13‐year‐old loblolly pine (Pinus taeda) forest to elevated (ambient + 200 µL L−1) atmospheric CO2. Three identical fully instrumented plots were implemented as controls (ambient air only). We quantified root dynamics from October 1998 to October 1999 using minirhizotrons. In spite of 16% greater root lengths and 24% more roots per minirhizotron tube, the effects of elevated atmospheric CO2 on root lengths and numbers were not statistically significant. Similarly, production and mortality were also unaffected by the CO2 treatment, even though annual root production and mortality were 26% and 46% greater in elevated compared to ambient CO2 plots. Average diameters of live roots present at the shallowest soil depth were, however, significantly enhanced in CO2‐enriched plots. Mortality decreased with increasing soil depth and the slopes of linear regression lines (mortality vs. depth) differed between elevated and ambient CO2 treatments, reflecting the significant CO2 by depth interaction. Relative root turnover (root flux/live root pool) was unchanged by exposure to elevated atmospheric CO2. Results from this study suggest modest, if any, increases in ecosystem‐level root productivity in CO2‐enriched environments.
Assessing effects of forecasted climate change on the diversity and distribution of European higher plants for 2050
Authors: Bakkenes M. , Alkemade J. R. M. , Ihle F. , Leemans R. , Latour J. B.
Published: March 2003

The rapidly increasing atmospheric concentrations of greenhouse gases may lead to significant changes in regional and seasonal climate patterns. Such changes can strongly influence the diversity and distribution of species and, therefore, affect ecosystems and biodiversity. To assess these changes we developed a model, called euromove. The model uses climate data from 1990 to 2050 as compiled from the image 2 model, and determines climate envelopes for about 1400 plant species by multiple logistic regression analysis. The climate envelopes were applied to the projected climate to obtain predictions about plant diversity and distributions by 2050. For each European grid cell, euromove calculates which species would still occur in forecasted future climate conditions and which not. The results show major changes in biodiversity by 2050. On average, 32% of the European plant species that were present in a cell in 1990 would disappear from that cell. The area, in which 32% or more of the 1990 species will disappear, takes up 44% of the modelled European area. Individual responses of the plant species to the forecasted climate change were diverse. In reviewing possible future trends, we found that plant species, in general, would find their current climate envelopes further northeast by 2050, shifting ranges that were comparable with those ranges in other studies.
Acclimation of photosynthesis and respiration to elevated atmospheric CO2 in two Scrub Oaks
Authors: Hymus Graham J. , Snead Tom G. , Johnson David P. , Hungate Bruce A. , Drake Bert G.
Published: March 2003

Abstract For two species of oak, we determined whether increasing atmospheric CO2 concentration (Ca) would decrease leaf mitochondrial respiration (R) directly, or indirectly owing to their growth in elevated Ca, or both. In particular, we tested whether acclimatory decreases in leaf‐Rubisco content in elevated Ca would decrease R associated with its maintenance. This hypothesis was tested in summer 2000 on sun and shade leaves of Quercus myrtifolia Willd. and Quercus geminata Small. We also measured R on five occasions between summer 1999 and 2000 on leaves of Q. myrtifolia. The oaks were grown in the field for 4 years, in either current ambient or elevated (current ambient + 350 µmol mol−1) Ca, in open‐top chambers (OTCs). For Q. myrtifolia, an increase in Ca from 360 to 710 µmol mol−1 had no direct effect on R at any time during the year. In April 1999, R in young Q. myrtifolia leaves was significantly higher in elevated Ca—the only evidence for an indirect effect of growth in elevated Ca. Leaf R was significantly correlated with leaf nitrogen (N) concentration for the sun and shade leaves of both the species of oak. Acclimation of photosynthesis in elevated Ca significantly reduced maximum RuBP‐saturated carboxylation capacity (Vc max) for both the sun and shade leaves of only Q. geminata. However, we estimated that only 11–12% of total leaf N was invested in Rubisco; consequently, acclimation in this plant resulted in a small effect on N and an insignificant effect on R. In this study measurements of respiration and photosynthesis were made on material removed from the field; this procedure had no effect on gas exchange properties. The findings of this study were applicable to R expressed either per unit leaf area or unit dry weight, and did not support the hypothesis that elevated Ca decreases R directly, or indirectly owing to acclimatory decreases in Rubisco content.
Interacting elevated CO2 and tropospheric O3 predisposes aspen (Populus tremuloides Michx.) to infection by rust (Melampsora medusae f. sp. tremuloidae)
Authors: Karnosky D. F. , Percy Kevin E. , Xiang Bixia , Callan Brenda , Noormets Asko , Mankovska Blanka , Hopkin Anthony , Sober Jaak , Jones Wendy , Dickson R. E. , Isebrands J. G.
Published: March 2003

We investigated the interaction of elevated CO2 and/or (Ozone) O3 on the occurrence and severity of aspen leaf rust (Melampsora medusae Thuem. f. sp. tremuloidae) on trembling aspen (Populus tremuloides Michx.). Furthermore, we examined the role of changes in leaf surface properties induced by elevated CO2 and/or O3 in this host–pathogen interaction. Three‐ to five‐fold increases in levels of rust infection index were found in 2 consecutive years following growing‐season‐long exposures with either O3 alone or CO2 + O3 depending on aspen clone. Examination of leaf surface properties (wax appearance, wax amount, wax chemical composition, leaf surface and wettability) suggested significant effects by O3 and CO2 + O3. We conclude that elevated O3 is altering aspen leaf surfaces in such a way that it is likely predisposing the plants to increased infection by aspen leaf rust.
Steps towards justice for people with learning disabilities as victims of crime: the important role of the police
Authors: Sharp Hannah
Published: March 2003

During 1999, Mencap, Values Into Action and Enable jointly conducted the first UK‐wide inquiry into the harassment, victimization and bullying of people with learning disabilities (LDs). Only 17% of participants in the inquiry reported incidents of crimes against them to the police according to a 1999 Mencap report. Values Into Action has continued its involvement in this project on crime, harassment and people with LDs. Since the UK inquiry, the project has examined the developmental work required by the police to respond adequately to the reports which they receive from people with LDs who may be victims. The present paper outlines: (1) the key findings of the Mencap inquiry; (2) some of the difficulties experienced by people with LDs in reporting possible crimes to the police; and (3) the recent changes in policy and law which have the potential to improve radically how people with LDs experience contact with the police and thereby improve their access to the criminal justice system.