bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetic neuropathy is associated with activation of the TNF‐α system in subjects with type 1 diabetes mellitus
Authors: González‐Clemente J. M. , Mauricio D. , Richart C. , Broch M. , Caixàs A. , Megia A. , Giménez‐Palop O. , Simón I. , Martínez‐Riquelme A. , Giménez‐Pérez G. , Vendrell J.
Published: September 2005

Objective  The development of diabetic neuropathy (DN) is predicted by cardiovascular risk factors associated with insulin resistance. As inflammation seems to be implicated in the pathogenesis of insulin resistance, we investigated whether subjects with type 1 diabetes mellitus (T1DM) and DN have an increase in plasma concentrations of inflammatory proteins involved in insulin resistance.

Design  Cross‐sectional.

Patients  One hundred twenty subjects, all diagnosed with T1DM 14 years before.

Measurements  (1) Sex, age, body mass index, waist‐to‐hip ratio (WHR), blood pressure, smoking, alcohol intake, insulin dose, HbA1c and lipid profile; (2) DN (peripheral and cardiac autonomic), retinopathy and nephropathy; (3) plasma concentrations of soluble fractions of tumour necrosis factor α receptors 1 and 2 (sTNFR1 and sTNFR2), interleukin‐6, high‐sensitive C‐reactive protein, adiponectin and leptin; and (4) insulin resistance (by way of a mathematical estimation of the glucose disposal rate – eGDR‐).

Results  Thirty‐six subjects had DN and 84 did not. Subjects with DN received higher insulin doses (57·6 ± 16·7 vs. 49·2 ± 15·0 IU/day; P = 0·008) and had higher WHR (0·85 ± 0·07 vs. 0·81 ± 0·10; P = 0·007) and HbA1c values (8·5 (7·6–9·6) vs. 7·7 (7·3–8·9)%; P = 0·049) than subjects without DN. They also had higher values of sTNFR1 (2·42 ± 0·60 vs. 1·96 ± 0·66 µg/l; P = 0·001) and sTNFR2 (4·73 ± 1·33 vs. 4·14 ± 1·09 µg/l; P = 0·015), and were more insulin resistant (eGDR values: 7·28 (5·83–8·03) vs. 8·30 (7·17–9·03) mg kg−1 min−1; P = 0·003). The relationship between DN and either sTNFR1 or sTNFR2 remained essentially unchanged after adjusting for several confounders, including glycaemic control, WHR, lipid profile, blood pressure and other microvascular complications (OR for sTNFR1: 2·592 (1·222–5·498), P = 0·013; OR for sTNFR2: 2·124 (1·258–3·587), P = 0·005).

Conclusions  The activity of the TNF‐α system is increased in subjects with type 1 diabetes mellitus and diabetic neuropathy, regardless of their glycaemic control and cardiovascular risk factors associated with insulin resistance. These results suggest that TNF‐α may play a pathogenic role in the development of diabetic neuropathy.
Instruments used in measuring symptoms, health status and quality of life in hypothyroidism: a systematic qualitative review
Authors: Razvi Salman , McMillan Carolyn V. , Weaver Jolanta U.
Published: September 2005

Background  Symptoms of hypothyroidism are varied and nonspecific, thereby making clinical diagnosis impossible. Some patients report ongoing symptoms despite treatment. Measuring symptoms, health status and quality of life by using appropriate instruments, in addition to biochemical tests, is therefore vital to quantify disease severity and assess response to treatment. A number of instruments have been used in hypothyroidism, leading to lack of clarity about what exactly is being measured, and the rationale for the inclusion of particular measures is often uncertain.

Objectives  To evaluate and compare instruments used in hypothyroidism in assessing patient‐reported outcomes.

Data sources and study selection  All published literature on MEDLINE until March 2005 was searched using the keywords ‘hypothyroidism’, ‘symptoms’, ‘quality of life’ and ‘health status’. Articles reporting controlled trials or instrument design and development were analysed to assess the instruments used and to ascertain whether they were measuring the stated outcome.

Data synthesis  Available tools to measure symptoms, health status and quality of life in diagnosis and management of hypothyroidism are discussed. We also describe how these tools have been described in published clinical trials along with the advantages and possible pitfalls of each of the commonly used tools.

Conclusions  Some instruments reviewed have not been suited to the outcome being studied, thereby giving rise to questionable results. This review should be useful for clinicians, researchers and patient‐support groups in understanding the principles behind these tools and the results obtained from their use in clinical practice, and in selecting measures for their own use.
The palaeoenvironment of humans and marine birds of the Aleutian Islands: three millennia of change
Authors: CAUSEY DOUGLAS , CORBETT DEBRA G. , LEFÈVRE CHRISTINE , WEST DIXIE L. , SAVINETSKY ARKADY B. , KISELEVA NINA K. , KHASSANOV BULAT F.
Published: September 2005

A unique window into the biological history of the Aleutian Islands is provided by the zooarchaeology of early human sites. We focus on the palaeoavifauna hunted by early Aleuts who inhabited Amchitka and Buldir islands (central Aleutians), and Shemya Island (western Aleutians) fromc.3500 yr ago to the present. Most of the seabird species recovered from these early sites varied widely in distribution and abundance through time and space. Pelagic procellariids such as short‐tailed albatrosses and short‐tailed shearwaters were present and abundant at most sites and at most times. During periods of increased temperatures and precipitation (e.g. 650–1100 yr bp), nearshore foragers such as cormorants and parakeet auklets increased in abundance, but during periods of cooling (e.g. 1800–2100 yr bp), piscivorous birds feeding offshore, such as murres and kittiwakes, predominated. Over three millennia, we found that marine bird populations were negatively correlated with temperature and positively correlated with precipitation. We detected hunter‐related depletions of populations breeding in accessible colonies at small scales of space and time, but we did not observe widespread or long‐term effects. We conclude that local oceanography and regional changes in prey bases caused by environmental and climate change in the past had a significant impact on the distribution and abundance of Aleutian marine birds.
Marine environment of the eastern and central Aleutian Islands
Authors: LADD CAROL , HUNT GEORGE L. , MORDY CALVIN W. , SALO SIGRID A. , STABENO PHYLLIS J.
Published: September 2005

To examine the marine habitat of the endangered western stock of the Steller's sea lion (Eumetopias jubatus), two interdisciplinary research cruises (June 2001 and May to June 2002) measured water properties in the eastern and central Aleutian Passes. Unimak, Akutan, Amukta, and Seguam Passes were sampled in both years, and three additional passes (Umnak, Samalga, and Tanaga) were sampled in 2002. In the North Pacific (and to a lesser extent in the Bering Sea), a strong front in water properties was observed near Samalga Pass in June of both years, with significantly warmer, fresher, and more nitrate‐poor water east of Samalga Pass than west of the pass. These water properties reflect differences in source waters (Alaska Coastal Current versus Alaskan Stream), mixing depth, and Bering Sea influence. Strong cross‐Aleutian gradients were also observed with warmer, fresher water on the North Pacific side of the archipelago. The nutrient content of the waters flowing through the passes, combined with the effects of mixing within the passes, influences the transport of nutrients into the Bering Sea. As water moves away from the strong mixing of the passes and becomes more stratified, phytoplankton can take advantage of the enhanced nutrient concentrations. Thus, the northern side of the Aleutian Islands (especially in the lee of the islands) appears to be more productive. Combined with evidence of coincident changes in many ecosystem parameters near Samalga Pass, it is hypothesized that Samalga Pass forms a physical and biogeographic boundary between the eastern and central Aleutian marine ecosystems.
Hydrographic features and seabird foraging in Aleutian Passes
Authors: LADD CAROL , JAHNCKE JAIME , HUNT GEORGE L. , COYLE KENNETH O. , STABENO PHYLLIS J.
Published: September 2005

Strong tidal currents crossing over the abrupt topography of the Aleutian Passes result in regions with high horizontal property gradients. These frontal regions vary with the tidal cycle and form the boundary between vertically mixed and stratified regions. Concentrations of seabirds were associated with convergence zones in the mixed water (MW) and with the front between North Pacific (NP) water and MW. Species that were foraging by picking at prey from the surface were associated with surface convergences that appeared to be associated with Langmuir circulation cells or tidal features (all fulmar aggregations) in the central passes (Samalga, Seguam). In contrast, subsurface foraging puffins and small alcids were mostly observed in areas of turbulent, well‐mixed water near the shallow regions of the passes. Short‐tailed shearwater flocks that were plunge‐diving for prey were associated with the front between the NP water and MW in the passes. On our transects, we observed no significant aggregations of seabirds associated with Bering Sea water or NP water away from the frontal zones. The interaction of strong currents with bathymetric features results in zones of vertical advection, mixing, and surface convergences that make island passes attractive foraging regions for seabirds. Deep passes lacking these features, such as many of the passes in the western Aleutian Archipelago, are not as likely to facilitate trophic transfer to top predators as shallow passes, such as those found in the eastern Aleutian Islands.
Patterns of host use in two African mistletoes: the importance of mistletoe–host compatibility and avian disperser behaviour
Authors: ROXBURGH L. , NICOLSON S. W.
Published: September 2005

Mistletoe infection prevalence typically differs between host tree species. Differences in infection prevalence between hosts are probably the product of mistletoe–host compatibility and frequency of seed deposition on that host by dispersers.

We recorded patterns of infection prevalence of two mistletoes, Phragmanthera dschallensis Engl. and Plicosepalus kalachariensis Schinz (Loranthaceae), on different host species. We then tested the importance of mistletoe–host compatibility mechanisms and disperser preferences in determining infection prevalence patterns among different host species.

Mistletoe–host compatibility was tested by planting mistletoe seeds on different hosts and recording germination and establishment up to 1 year after planting. There were no significant differences in seed germination, but seedling survival was significantly different among hosts. However, seedling survival was not correlated with infection prevalence among hosts.

Disperser preferences were calculated from observations of birds that disperse mistletoe fruits. Both the duration and frequency of disperser visits to trees were greater among parasitized trees. Dispersers did not visit unparasitized trees in proportion to their abundance, but showed preferences for certain tree species. Disperser preferences for trees were correlated with infection prevalence.

Mistletoe–host compatibility mechanisms could not explain patterns of prevalence among hosts in this study. In contrast, disperser preferences were related to prevalence of mistletoe infections among different host tree species.
Short‐term energy regulation in nectar‐feeding birds: the response of Whitebellied Sunbirds (Nectarinia talatala) to a midday fast
Authors: NICOLSON S. W. , HOFFMANN D. , FLEMING P. A.
Published: September 2005

Small nectar‐feeding birds have high energy turnover and must respond rapidly to changes in food concentration or feeding opportunities. A previous study showed that Rufous Hummingbirds (Selasphorus rufus) were unable to adjust their intake rates after a midday fast and thus ended the day with energy deficits that necessitated the use of torpor.

We examined the ability of Whitebellied Sunbirds (Nectarinia talatala) to cope with a similar loss of foraging time (lights out from 10.00 h to 12.00 h). During the experiment, birds were kept at 10 °C and fed 20% w/w sucrose solution.

In contrast to hummingbirds, sunbirds increased their rate of afternoon feeding following the fast, consuming 14·3 ± SD 10·0% (n = 8) more than on the afternoon of the control day, and maintaining evening body mass at control levels. However, morning body mass on the third day was significantly lower than on the previous 2 days, indicating that compensation for reduced feeding time was probably incomplete. Nectar‐feeding birds show varied and flexible responses to energy challenges.
Basic and clinical pharmacology of new motility promoting agents
Authors: Galligan J. J. , Vanner S.
Published: September 2005

Abstract Recent research has provided new information about drugs that could be used to treat functional motility disorders. Promotility drugs accelerate gastric emptying or colonic transit and these properties may contribute to their efficacy in treating symptoms associated with gastroparesis, functional dyspepsia or constipation. 5‐Hydroxytryptamine4 receptors are targets for drugs (tegaserod, renzapride) that treat symptoms in constipated irritable bowel syndrome patients and in gastroparesis. Drugs acting at motilin (erythromycin) and cholecystokinin‐1 (dexloxiglumide) receptors accelerate gastric emptying. Dexloxiglumide might be useful in the treatment of functional dyspepsia particularly that associated with lipid intake. Alvimopan is aμ‐opioid receptor antagonist that does not cross the blood brain barrier. Alvimopan is effective in treating postsurgical ileus and perhaps opiate‐induced bowel dysfunction. Successes and failures of recent efforts to develop promotility agents revealed opportunities and challenges for developing new promotility drugs. The pharmacological properties of partial agonists might be exploited to develop effective promotility drugs. However, opposing actions of promotility agents on motility (increased contractionvsdecreased accommodation) limit the clinical efficacy of drugs with these opposing actions. Selection of appropriate patient populations for evaluation of new drugs is also critical.
Immunohistochemical localization of substance P NK1 receptor in guinea pig distal colon
Authors: Harrington A. M. , Hutson J. M. , Southwell B. R.
Published: September 2005

Abstract  Background:  Neurokinin receptors facilitate tachykinin mediated intestinal motility and secretion. Distribution of Substance P (SP) neurokinin 1 receptor (NK1r) immunoreactivity (IR) has been previously characterized in guinea pig ileum, but not colon. This study localizes NK1rs in guinea pig distal colon.

Methods:  Neurons were double labelled for NK1r and either acetylcholine transferase (ChAT), calbindin (calb), neuropeptide Y (NPY), nitric oxide synthase (NOS) or SP. The NK1r endocytosis was induced by 10−5 mol L−1 SP, septide, [SarMet] SP or neurokinin A.

Results:  In guinea pig distal colon, NK1r–IR was present on 70% of submucosal neurons. Sixty‐threepercent of the NK1r–IR submucosal neurons were ChAT–IR, 16% calb/SP–IR, 19% NPY–IR and 14% NOS–IR neurons. The NK1r–IR was present on 5% of myenteric neurons. Of these 63% were ChAT–IR, 16% calb–IR neurons and 25% NOS–IR. The NK1rs were also on myenteric plexus interstitial cells of Cajal and on circular muscle.

Conclusion:  In guinea pig distal colon, NK1rs were on 70% of submucosal neurons including all three secretomotor neuron subtypes and sensory neurons, suggesting NK1rs have a major role in neuronal control of mucosal reflexes. The NK1rs were on few myenteric neurons but were dense on muscle cells, suggesting NK1rs affect motility through neuro‐muscular rather than neuro‐neuronal transmission.
Motor patterns and propulsion in the rat intestine in vivo recorded by spatio‐temporal maps
Authors: Ferens D. M. , Chang E. C. , Bogeski G. , Shafton A. D. , Kitchener P. D. , Furness J. B.
Published: September 2005

Abstract  We have used spatio‐temporal maps derived from video images to investigate propagated contractions of the rat small intestine in vivo. The abdomen, including an exteriorized segment of jejunum, was housed in a humid chamber with a viewing window. Video records were converted to spatio‐temporal maps of jejunal diameter changes. Intraluminal pressure and fluid outflow were measured. Contractions occupied 3.8 ± 0.2 cm of intestine and propagated anally at 3.1 ± 0.2 mm s−1 when baseline pressure was 4 mmHg. Contractions at any one point lasted 8.7 ± 0.6 s. Contractions often occurred in clusters; within cluster frequencies were 2.28 ± 0.04 min−1. Pressure waves, with amplitudes greater than about 9 mmHg, expelled fluid when the baseline pressure was 4 mmHg. In the presence ofl‐NAME, circular muscle contractions occurred at a high frequency, but they were not propagated. We conclude that video recording methods give good spatio‐temporal resolution of intestinal movement when applied in vivo. They reveal neurally‐mediated propulsive contractions, similar to those previously recorded from intestinal segments in vitro. The propagated contractions had speeds of propagation that were slower and frequencies of occurrence that were less than speeds and frequencies of slow waves in the rat small intestine.
Classical conditioned response of rectosigmoid motility and regional cerebral activity in humans
Authors: Kanazawa M. , Endo M. , Yamaguchi K. , Hamaguchi T. , Whitehead W. E. , Itoh M. , Fukudo S.
Published: September 2005

Abstract  The relationship between the central processes of classical conditioning and conditioned responses of the gastrointestinal function is incompletely understood in humans. We tested the hypothesis that the rectosigmoid motility becomes conditioned with anticipatory painful somatosensory stimulus and that characteristic brain areas become activated during anticipation. In nine right‐handed healthy male subjects, a loud buzzer (CS, conditional stimulus) was paired with painful transcutaneus electrical nerve stimulation to the right hand (unconditional stimulus). Rectosigmoid muscle tone measured by the barostat as the intrabag volume, phasic contractions of the bowel measured as the number of phasic volume events (PVEs), and regional cerebral blood flow assessed by positron emission tomography (PET), were measured before and after conditioning. Following conditional trials, the bag volume after CS alone did not show significant changes between before and after the stimulus, but the number of PVEs after 2‐minute interval of the CS alone was significantly greater than that before the stimulus (P < 0.05). The PET data showed the conditioning elicited significant cerebral activation of the prefrontal, anterior cingulate, parietal and insula cortices (P ≤ 0.001, uncorrected). Rectosigmoid motility can be conditioned with increase in phasic contractions in humans.
μ‐Opiate receptor agonist loperamide blocks bethanechol‐induced gallbladder contraction, despite higher cholecystokinin plasma levels in man
Authors: Otto B. , Mawe G. M. , Riepl R. L.
Published: September 2005

Abstract  μ‐Opiate receptor agonists, such as loperamide, influence biliary excretion and suppress cholecystokinin (CCK)‐induced gallbladder contraction. Loperamide decreases cholinergic mechanisms, like pancreatic polypeptide (PP) release, while muscarinic agonist (bethanechol)‐induced PP release remains unaffected. The effects of loperamide on gallbladder contraction and peptide release were performed to resolve this discrepancy.

Methods:  Six subjects (27.6 ± 2.0 years) received bethanechol (12.5, 25 and 50 μg kg−1 h−1 continuously over 40 min) after oral 16 mg loperamide (vs placebo) in a crossover design. Gallbladder volume and plasma levels of CCK, PP, motilin, gastrin, neurotensin, cholylglycine were measured regularly.

Results:  Bethanechol significantly reduced gallbladder volume (26.7 ± 1.9 to a nadir of 15.3 ± 2.2 mL, P ≤ 0.05), and this action was inhibited by loperamide. Basal CCK levels increased significantly after loperamide. Incremental integrated CCK release after bethanechol was higher under loperamide (P ≤ 0.05), as placebo CCK release was significantly decreased under bethanechol (2.0 ± 0.4–0.8 ± 0.3 pmol L−1). In both settings, PP levels were significantly increased after bethanechol, while release of neurotensin, motilin, gastrin and cholylglycine was unaffected.

Conclusion:  The μ‐opiate receptor agonist loperamide inhibits bethanechol‐induced gallbladder contraction. This effect is not mediated by inhibition of CCK release, as loperamide even enhances basal CCK plasma levels. As cholinergic mechanisms, like bethanechol‐induced incremental PP release, were unaffected, μ‐opiate agonists might influence gallbladder contraction via vagal–cholinergic pathways.
A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating
Authors: Kim H. J. , Vazquez Roque M. I. , Camilleri M. , Stephens D. , Burton D. D. , Baxter K. , Thomforde G. , Zinsmeister A. R.
Published: September 2005

Abstract  Aim:  To evaluate the effects of a combination probiotic on symptoms and colonic transit in patients with irritable bowel syndrome (IBS) and significant bloating.

Methods:  Forty‐eight patients with Rome II IBS were randomized in a parallel group, double‐blind design to placebo or VSL# 3 twice daily (31 patients received 4 weeks and 17 patients 8 weeks of treatment). Pre‐ and post‐treatment colonic transit measurements were performed using scintigraphy with 111In charcoal. Symptoms were summarized as an average daily score for the entire period of treatment and separately for the first 4 weeks of treatment. Weekly satisfactory relief of abdominal bloating was assessed.

Results:  Treatment with VSL# 3 was associated with reduced flatulence over the entire treatment period (placebo 39.5 ± 2.6 vs VSL# 3 29.7 ± 2.6, P = 0.011); similarly, during the first 4 weeks of treatment, flatulence scores were reduced (placebo 40.1 ± 2.5 vs VSL# 3 30.8 ± 2.5, P = 0.014). Proportions of responders for satisfactory relief of bloating, stool‐related symptoms, abdominal pain and bloating scores were not different. Colonic transit was retarded with VSL# 3 relative to placebo (colon geometric center 2.27 ± 0.20 vs 2.83 ± 0.19, P = 0.05 respectively).

Conclusion:  VSL# 3 reduces flatulence scores and retards colonic transit without altering bowel function in patients with IBS and bloating.
Two Doses of Parenterally Administered Split Influenza Virus Vaccine Elicited High Serum IgG Concentrations which Effectively Limited Viral Shedding upon Challenge in Mice
Authors: Hovden A.‐O. , Cox R. J. , Madhun A. , Haaheim L. R.
Published: September 2005

We have previously found that whole influenza virus vaccine induced a more rapid and stronger humoral response, particularly after the first dose of vaccine, than split virus vaccine in mice. In this study, we have evaluated the protective efficacy of whole and split influenza virus vaccines in mice using a nonlethal upper respiratory tract challenge model. We have also investigated the immunological correlates associated with no or very little viral shedding after viral challenge. Vaccination resulted in reduced viral shedding and shortened the duration of infection by at least 2 days. After one dose of vaccine, whole virus vaccine generally resulted in less viral shedding than split virus vaccine. In contrast, two doses of split virus vaccine, particularly the highest vaccine strengths of 15 and 30 µg HA, most effectively limited viral replication and these mice had high concentrations of prechallenge influenza‐specific serum IgG. The vaccine formulation influenced the IgG2a/IgG1 ratio, and this IgG subclass profile was maintained upon challenge to some extent, although it did not influence the level of viral shedding. The concentration of postvaccination serum IgG showed an inverse relationship with the level of viral shedding after viral challenge. Therefore, serum IgG is an important factor in limiting viral replication in the upper respiratory tract upon challenge of an antigenically similar virus.
Tissue Localization of Toll‐Like Receptors in Biopsy Specimens of Liver from Children Infected with Hepatitis C Virus
Authors: Mozer‐Lisewska I. , Sluzewski W. , Kaczmarek M. , Jenek R. , Szczepanski M. , Figlerowicz M. , Kowala‐Piaskowska A. , Zeromski J.
Published: September 2005

Toll‐like receptors (TLR) are important tools of innate immunity, localized mainly on cells of the immune system, but also have been shown on cells of other origin. In the current study, they have been searched in biopsy specimens of liver from children bearing chronic viral hepatitis of C type (HCV). TLR2, TLR3 and TLR4 were traced by means of polyclonal antibodies and avidin‐biotin complex (ABC) immunohistochemistry. Besides, mRNA for TLR was looked for using specific primers and polymerase chain reaction. Several controls, including neutralization of primary antibody with respective blocking peptide, confirmed the specificity of the immunohistochemical reaction. All TLR tested could be visualized in a focal distribution in single hepatocytes and some cells of inflammatory infiltrates. There was no reaction whatsoever in liver samples not infected with hepatotropic virus. In molecular studies, mRNA for TLR2 and TLR4 was detected in both noninfected and hepatitis B virus‐infected established cell lines of human hepatoma as well as in HCV+ biopsy samples. These data indicate that TLR can be traced in liver cells, both at the protein and at the mRNA level. Their irregular and focal distribution in HCV+, but not in HCV–, liver suggests some role of TLR in the pathogenesis of chronic viral hepatitis, at least in children.
The Immunogenicity of a Conformationally Restricted Peptide Mimetic of Meningococcal Lipooligosaccharide
Authors: Tiwana H. , Clow K. J. , Hall C. , Feavers I. M. , Charalambous B. M.
Published: September 2005

Life‐threatening meningitis and septicaemia caused by Neisseria meningitidis are a public health priority, and their prevention by vaccination is a major objective. Meningococcal capsular polysaccharide‐based vaccines are effective against the major invasive serogroups, except for serogroup B, the capsule of which mimics human polysaccharides and is poorly immunogenic. An alternative vaccine candidate that has the potential to offer cross‐protection against antigenically diverse meningococci is the lipooligosaccharide (LOS). The structurally constrained peptide mimetic, C22, of a bactericidal antibody epitope within LOS was previously shown to elicit cross‐reactive antibodies to meningococcal LOS when complexed to NeutrAvidin™ as a carrier protein. The immunogenicity of this antigen in H‐2d (BALB/c) and H‐2k (C3H/HeN) haplotype mice was further investigated. Anti‐LOS immunoglobulin G (IgG) antibody titres increased with the vaccine dose and correlated with the anti‐C22 peptide antibody titres in both haplotypes. Antigen‐stimulated Th1/Th2 cytokine secretion by splenocytes and antibody isotypes indicated a Th2‐type immune response with IgG1 antibodies and a low titre of IgG2b. There was no serum bactericidal activity observed against the meningococcus.
DNA Vaccination Using Bacillus Calmette‐Guerin‐DNA as an Adjuvant to Enhance Immune Response to Three Kinds of Swine Diseases
Authors: Zhang S. , Guo Y.‐J. , Sun S.‐H. , Wang K.‐Y. , Wang K.‐H. , Zhang Y. , Zhu W.‐J , Chen Z.‐H. , Jiang L.
Published: September 2005

In order to enhance the immune efficacy of DNA vaccination, experiments were conducted to investigate the regulating effects of Bacillus Calmette‐Guerin (BCG)‐DNA as an adjuvant on immune responses of mice against foot‐and‐mouth disease (FMD), Aujeszky's disease (AjD) and classical swine fever (CSF). BCG‐DNA was purified from BCG by ion‐exchange chromatography. Three DNA vaccines (pVSG, pVgD and pVE2) against the respective infection were constructed, and BCG‐DNA was coimmunized to mice by muscle injection. The results showed that titres of specific immunoglobulin (Ig)G to the vaccines mounted remarkably in the sera of the adjuvant covaccinated mice (P < 0.01). Antibody isotype IgG2a and IgG1 also increased, respectively, in mice coimmunized with BCG‐DNA compared with those of the control groups (P < 0.01). Cellular immune cytokine interferon‐γ and cytotoxic T lymphocytes were detected in coimmunized BCG‐DNA groups (P < 0.05). Whereas interleukin‐4, humoral immune cytokine, was not significant (P > 0.05). These results suggest that codelivery of BCG‐DNA with DNA vaccines against FMD, AjD and CSF can enhance the induction of antigen‐specific, especially, cell‐mediated immunity.
The downregulation of FLOWERING LOCUS C (FLC) expression in plants with low levels of DNA methylation and by vernalization occurs by distinct mechanisms
Authors: Jean Finnegan E. , Kovac Kathryn A. , Jaligot Estelle , Sheldon Candice C. , James Peacock W. , Dennis Elizabeth S.
Published: September 2005

FLOWERING LOCUS C (FLC), a repressor of flowering, is a major determinant of flowering time in Arabidopsis. FLC expression is repressed by vernalization and in plants with low levels of DNA methylation, resulting in early flowering. This repression is not associated with changes of DNA methylation within the FLC locus in either vernalized plants or plants with low levels of DNA methylation. In both cases, there is a reduction of histone H3 trimethyl‐lysine 4 (K4) and acetylation of both histones H3 and H4 around the promoter‐translation start of FLC. The expression of the two genes flanking FLC is also repressed in both conditions and repression is associated with decreased histone H3 acetylation. The changes in histone modifications at the FLC gene cluster, which are similar in vernalized plants and in plants with reduced DNA methylation, must arise by different mechanisms. VERNALIZATION 1, VERNALIZATION 2 and VERNALIZATION INSENSITIVE 3 modulate FLC expression in vernalized plants; these proteins play no role in the downregulation of FLC in plants with low levels of DNA methylation. Chimeric FLC::GUS transgenes respond to vernalization but these same transgenes show a position‐dependent response to low levels of DNA methylation. In plants with reduced DNA methylation, expression of the five MADS AFFECTING FLOWERING (MAF) genes is repressed, suggesting that DNA methylation alters the expression of a trans‐acting regulator common to FLC and members of the related MAF gene family. Our observations suggest that DNA methylation is not part of the vernalization pathway.
Is malaria a disease of poverty? A review of the literature
Authors: Worrall Eve , Basu Suprotik , Hanson Kara
Published: September 2005

Objective  To review the evidence on the link between malaria and poverty.

Methods  Review of the published and grey literature to identify (i) the data available on the socio‐economic distribution of malaria incidence and vulnerability, and (ii) the uptake of malaria control interventions.

Results  We found mixed evidence on malaria incidence, with a number of studies identifying no relationship between socio‐economic status and incidence, although a larger number of studies do find a link. There is strong evidence that uptake of preventive and treatment interventions is closely related to proxies for socio‐economic status. More generally, the quality of the literature examining this issue is highly variable, with many different measures of socio‐economic status and often inadequate descriptions of methods of data collection and analysis in relation to socio‐economic status.

Conclusions  Important socio‐economic differentials exist in access to malaria interventions, increasing the vulnerability of the poorest. More information is needed about how other methods of delivering malaria treatment and prevention can redress these inequalities.
Diagnostic values of IgG4 in human gnathostomiasis
Authors: Anantaphruti Malinee T. , Nuamtanong S. , Dekumyoy P.
Published: September 2005

The diagnostic values of immunoglobulin G subclass antibodies from patients with gnathostomiasis were assessed by immunoblot technique. Antigen was prepared from crude extracts of Gnathostoma spinigerum advanced third‐stage larvae obtained from naturally infected eels. The sera were obtained from 14 parasite‐confirmed gnathostomiasis cases, 63 patients with other helminthic infections and 13 healthy controls. Nine prominent IgG4 reactive bands appeared with molecular weights of 94, 51, 47, 43, 38, 24, 21, 20 and 15 kDa. The diagnostic sensitivity of each of the nine reactive bands ranged from 100% to 64.3% in 14 parasite‐confirmed gnathostomiasis cases. All (100%) confirmed cases recognized the 21 kDa antigenic band, but not other helminthic infections or parasite‐free control. Recognition of 21 kDa antigen in G. spinigerum advanced third‐stage larvae crude extracts is the most specific diagnostic marker for human gnathostomiasis, with 100% sensitivity and specificity. The 20 and 24 kDa protein bands were additional diagnostic bands for confirming diagnosis of infection where the 21 kDa band was faint. No specific binding of IgG1, IgG2, or IgG3 antibodies was observed in any sera from confirmed gnathostomiasis cases.
Non‐specific effects of vaccination on child survival? A prospective study in Senegal
Authors: Elguero Eric , Simondon Kirsten B. , Vaugelade Jacques , Marra Adama , Simondon François
Published: September 2005

Objectives  Several studies have shown an association between vaccination and child mortality in developing countries. The present paper examines this issue using data from a Senegalese rural area which has been monitored from 1983 to the present.

Methods  We analysed two birth cohorts, comprising 7796 and 3573 persons who had received either BCG and DTP (diphtheria‐tetanus‐pertussis) simultaneously or neither of these vaccines, and who had been followed from birth to 2 years of age. The association between vaccinations and mortality was assessed by Cox proportional hazards model.

Results  Mortality ratios for recipients of the BCG/DTP combination were 0.59 (95% CI: 0.46–0.74) for the first cohort and 0.70 (0.50–0.97) for the second cohort. Mortality ratios for measles vaccine recipients were 0.98 (0.75–1.27) for the first cohort and 0.87 (0.57–1.30) for the second cohort.

Conclusions  The BCG/DTP combination was associated with a reduction in mortality whereas measles vaccination was not associated with mortality.
Developing an evidence‐based, preventive care package for persons with HIV in Africa
Authors: Mermin Jonathan , Bunnell Rebecca , Lule John , Opio Alex , Gibbons Amanda , Dybul Mark , Kaplan Jonathan
Published: September 2005

Currently, 95% of the 40 million persons with HIV live in low and middle income countries; 27 million in sub‐Saharan Africa. HIV/AIDS is a leading cause of death in the region, yet access to care and treatment considered standard‐of‐care in the industrialized world is extremely limited. There is a need for standardized, evidence‐based recommendations on preventive measures. We developed a list of potential interventions based, when possible, on documented efficacy in reducing morbidity or mortality among persons with HIV in Africa. We considered the accessibility, affordability, and potential for implementation using existing health care infrastructure. Potential components included cotrimoxazole prophylaxis, safe drinking water, isoniazid prophylaxis, insecticide‐treated bed nets, micronutrients, and provision of HIV counseling and testing and condoms to family members of persons with HIV. There are several additional interventions for which further evaluation would be useful before inclusion in a standard package of care, including acyclovir prophylaxis, food supplementation, hand washing, and fluconazole prophylaxis. The provision of a basic care package could be an important step toward reducing health care disparities and gaining more control of the global HIV/AIDS epidemic.
Refraction, axial length and age‐related maculopathy
Authors: Ulvik Solveig Otteren , Seland Johan H. , Wentzel‐Larsen Tore
Published: September 2005

Purpose:  To study the relationship between age‐related maculopathy (ARM)/age‐related macular degeneration (AMD) and phakic refraction and between ARM/AMD and axial length.

Methods:  The study was a point prevalence study that included 663 randomly selected persons aged over 65 years. We measured axial length and refraction. Fundus images were graded for ARM according to a modified Wisconsin Age‐related Maculopathy Grading System standard. Data from both eyes were available from most participants. We analysed the results for both individual eyes and pairs.

Results:  The mean axial length was 23.22 mm for right eyes and 23.21 mm for left eyes. Women had a 0.57‐mm shorter mean axial length than men. The mean refraction was +1.0 dioptres (D) for right eyes and +0.9 D for left eyes. At 70 years of age women were more hypermetropic than men by 0.66 D. There was no significant difference in refraction or axial length among the groups with different ARM stages.

Conclusion:  We found no statistically significant relationship between axial length/refraction and AMD/ARM. There was a statistically significant sex difference in axial length and refraction, where women had shorter axial lengths and were more hypermetropic than men.
The functional genetic variation in the PTPN22 gene has a negligible effect on the susceptibility to develop inflammatory bowel disease
Authors: Martín Ma.C. , Oliver J. , Urcelay E. , Orozco G. , Gómez‐Garcia M. , López‐Nevot M.Á. , Piñero A. , Brieva J.A. , De La Concha E.G. , Nieto A. , Martín J.
Published: September 2005

Abstract:  The aim of this study was to assess the possible association between the protein tyrosine phosphatase non‐receptor 22 (PTPN22) gene 1858C→T (rs2476601, encoding R620W) polymorphism and inflammatory bowel disease (IBD). Our study population consisted of 1113 IBD [544 ulcerative colitis (UC) and 569 Crohn's disease (CD)] patients and 812 healthy subjects. All the individuals were of Spanish white origin. Genotyping of the PTPN22 gene 1858C→T polymorphism was performed by real time polymerase chain reaction technology, using TaqMan 5′‐allelic discrimination assay. The frequency of the PTPN22 1858T allele in healthy subjects was 6.2% compared with 6.7% in the UC patients and 5.1% in Crohn's patients. No statistically significant differences were observed when the PTPN22 1858C→T allele and genotype distribution among CD patients, UC patients and healthy controls were compared. These results indicate that the PTPN22 1858C→T polymorphism does not appear to play a major role in IBD predisposition in our population.
Haplotyping of TNFα gene promoter using melting temperature analysis: detection of a novel –856(G/A) mutation
Authors: Song Y. , Araki J. , Zhang L. , Froehlich T. , Sawabe M. , Arai T. , Shirasawa T. , Muramatsu M.
Published: September 2005

Tumor necrosis factor alpha (TNFα) is a potent cytokine with a wide range of pro‐inflammatory activities and plays a critical role in the pathogenesis of a number of infectious, inflammatory, autoimmune, and metabolic diseases. We determined four single‐nucleotide polymorphisms (SNPs), −1031(C/T), −863(C/A), −857(C/T), and −308(G/A) in the TNFα promoter region using melting temperature analysis, among 1451 geriatric autopsy samples. Two adjacent SNPs, −863(C/A) and −857(C/T), were directly assayed by a single probe reaction, which correctly determined three of four expected haplotypes. Sequence confirmation related that the most rare haplotype (8/2902 chromosomes, frequency: 0.26%) contains a novel mutation of −856(G/A), instead of the predicted haplotype. These results indicate that melting temperature analysis provides a robust method to determine the polymorphisms in the TNFα promoter.
Genetic diversity of KIR natural killer cell markers in populations from France, Guadeloupe, Finland, Senegal and Réunion
Authors: Denis L. , Sivula J. , Gourraud P.‐A. , Kerdudou N. , Chout R. , Ricard C. , Moisan J.‐P. , Gagne K. , Partanen J. , Bignon J.‐D.
Published: September 2005

Killer cell immunoglobulin‐like receptors (KIRs) belong to a diverse family of natural killer (NK) cell receptors recognizing human leukocyte antigen (HLA) class I molecules. Due to this functional link, KIR molecules are expected to display a high polymorphism, such as their HLA ligands. Moreover, many studies conducted in mouse and human models have shown that NK‐KIR receptors play an important role in haematopoietic stem cell transplantation (HSCT). A beneficial impact of peculiar KIR ligand (HLA) mismatching has been reported suggesting a role to this combinatory HLA‐KIR polymorphism. It is thus important to investigate KIR diversity in various human populations. To this end, we used polymerase chain reaction‐sequence‐specific primers to evaluate KIR gene in five selected populations (France, Guadeloupe, Senegal, Finland and Réunion). Genotypic and haplotypic frequencies were computed, as well as genetic distances and dendrogram (phylip package). These data illustrate the genetic relationship of these five populations through the KIR polymorphism. Results revealed a wide diversity in KIR gene frequencies in Guadeloupe and Réunion, and a high specificity in Senegal. The obtained dendrogram indicated small genetic distances between France, Guadeloupe and Réunion as well as between France and Finland. Senegal showed a distant genetic relationship with the other countries and, interestingly, an inverted ratio of coding/non‐coding (KIR2DS4/1D) alleles compared with Caucasians. These data expose the broad diversity in KIR genes worldwide and show that KIR genes are pertinent tools in human population genetics. If the role of KIR donor–recipient incompatibilities is confirmed, KIR diversity according to ethnicity should be taken into account during the selection of HSCT donors.
Distributions of HLA class I alleles and haplotypes in Northern Han Chinese
Authors: Hong W. , Fu Y. , Chen S. , Wang F. , Ren X. , Xu A.
Published: September 2005

Human leukocyte antigen (HLA) class I allelic genotypes were determined in 105 unrelated Han ethnic individuals inhabiting the northern China area. A total of 19 HLA‐A alleles, 49 HLA‐B alleles and 24 HLA‐Cw alleles were detected. Through the analyses of two and three loci haplotypes of HLA‐A, HLA‐B, and HLA‐C loci, 11 HLA‐A‐B‐Cw haplotypes, 19 HLA‐A‐B haplotypes, 18 HLA‐A‐Cw haplotypes, and 24 HLA‐B‐Cw haplotypes with the frequencies of higher than 0.01 were revealed. The Nei's genetic distance (GD) was estimated, and the NJ dendrogram showed that Northern Han had a higher GD to Southern Han (0.233) than those to the Korean (0.138) or other Northern ethnic groups, suggesting that Northern Han had more mixed blood with the ethnic groups originally in Northeast Asia. Our results provide useful information on the further study of evolution and relationships of Chinese ethnic groups and disease association in terms of HLA class I genes.
Influence of FcγRIIA and MBL polymorphisms on severe acute respiratory syndrome
Authors: Yuan F. F. , Tanner J. , Chan P. K. S. , Biffin S. , Dyer W. B. , Geczy A. F. , Tang J. W. , Hui D. S. C. , Sung J. J. Y. , Sullivan J. S.
Published: September 2005

Polymorphisms of human Fc γ‐receptor IIA (FcγRIIA) and mannose‐binding lectin (MBL) genes have been associated with susceptibility to or severity of some infectious diseases. In order to investigate whether these genetic factors might influence susceptibility to infection with the severe acute respiratory syndrome‐associated coronavirus (SARS‐Cov) as well as the course and severity of the infection, we evaluated polymorphisms of FcγRIIA and MBL genes in DNA samples from a group of approximately 180 people from Hong Kong who were infected with SARS‐Cov. These included 132 patients who had moderate course of SARS infection (home subgroup), 26 patients with a severe course requiring treatment in an intensive care ward (ICU subgroup) and a subgroup of 22 patients who died from SARS (deceased subgroup). A total of 200 normal blood donors from the same region were used as controls. A significant association was found between the FcγRIIA‐R/R131 genotype and a severe course of SARS, with higher frequency of homozygosity for FcγRIIA‐R/R131 in the ICU subgroup of SARS patients when compared with controls (P = 0.03; odds ratio: 3.2; 95% confidence interval: 1.1–9.1). In comparison with controls, a significant difference in linear trend distribution of FcγRIIA genotypes was seen among the severe SARS patients (ICU and deceased subgroups) without co‐morbidity, and the incidence of FcγRIIA‐H/H131 was lower in these patients as well. There were no significant differences in MBL genotypes and allele frequencies among SARS patients and controls. The study reveals that in addition to age and co‐morbidity, FcγRIIA polymorphism of individuals may also influence outcome after infection with the SARS‐Cov.
Human leukocyte antigen class I and II haplotypes and risk of cervical cancer
Authors: Carreon J. D. , Martin M. P. , Hildesheim A. , Gao X. , Schiffman M. , Herrero R. , Bratti M. C. , Sherman M. E. , Zaino R. J. , Carrington M. , Wang S. S.
Published: September 2005

Human leukocyte antigen (HLA) variations may affect immune response to human papillomavirus infection and subsequent cervical neoplasia risk. We investigated the frequency and relationship between HLA‐A‐B and HLA‐A‐B‐DR haplotypes among women with cervical cancer/high‐grade lesions (n = 365) and cytologically normal population controls (n = 681) within three cervical neoplasia studies in the US and Costa Rica. Notable differences in haplotype frequencies were observed; the HLA‐A*01‐B*08 haplotype occurred in >5% of US Caucasians but in <1% of Costa Ricans. The most prevalent HLA‐A*24‐B*40‐DR*04 haplotype in Costa Rica (5%) was found in <1% of US Caucasians. No HLA haplotype was significantly associated with cervical neoplasia, suggesting that individual allele associations reported to date (e.g. HLA‐DR*13) are not likely explained by underlying haplotypes.
Identification of HLA‐A*3101‐restricted cytotoxic T‐lymphocyte response to human immunodeficiency virus type 1 (HIV‐1) in patients with chronic HIV‐1 infection
Authors: Borghan M. A. , Oka S. , Takiguchi M.
Published: September 2005

Virus‐specific cytotoxic T‐lymphocyte (CTL) responses are critical in the control of human immunodeficiency virus type 1 (HIV‐1) infections. As several HIV‐1 CTL epitopes restricted to many HLA types are already known, we aimed at identifying the CTL epitopes restricted by HLA‐A*3101 in an effort to expand the epitope repertoire available for the development of potential T cell‐mediated therapeutic measures and protective vaccines. Scanning of HIV‐1 clade B SF2 strain proteins for the presence of peptides containing HLA‐A*3101‐binding motifs revealed 88 nine‐ to 11‐mer peptides that had been synthesized and assayed for binding to HLA‐A*3101 molecules. Peptides with medium to high HLA‐binding affinity were tested for their ability to stimulate a CTL response in the peripheral blood mononuclear cells (PBMCs) from selected HIV‐1‐infected patients. Two of these binding peptides, Env769–779 (RLRDLLLIAAR) and Nef192–200 (KLAFHHMAR), induced peptide‐specific CTLs in PBMCs from at least two of five HIV‐1‐seropositive individuals. CTL clones specific for the two peptides killed HLA‐A*3101‐expressing target cells infected with HIV‐1 recombinant vaccinia virus, indicating that these peptides were naturally processed HLA‐A*3101‐restricted CTL epitopes. Identification of T‐cell epitopes on HIV‐1 proteins will increase our understanding of the role of CD8+ T cells in HIV‐1 infections and assist in the design of new protective strategies.