bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired contrast sensitivity in adolescents and young Type 1 (insulin‐dependent) diabetic patients with microalbuminuria
Authors: Bangstad H.‐J. , Brinchmann‐Hansen O. , Hultgren S. , Dahl‐Jørgensen K. , Hanssen K. F.
Published: May 2009

Abstract. We compared neurosensorial visual function by psychophysical tests (macular recovery time and contrast sensitivity) in two well matched groups of young Type 1 (insulin‐dependent) diabetic patients with micro‐and normoalbuminuria, respectively. The patients had normal visual acuity (≥ 1.0) and either no retinopathy or non‐proliferative retinopathy. Thirty patients with microalbuminuria (albumin excretion ≥ 15 μg/min in a least two out of three timed overnight urine samples) were matched (age, diabetes duration, mean one‐year HbA1c, gender) with normoalbuminuric (n = 27) patients. Retinopathy (50° colour fundus photography) was assessed by counting microaneurysms and hemorrhages as ‘red spots’. Contrast sensitivity was examined for the spatial frequencies of 1.5, 3, 6, 12 and 18 cycles per degree (cpd). Macular recovery time (nyctometry) refers to the time‐related (2 min) ability of the retina to regain visual acuity following exposure to bright light (photostress). Contrast sensitivity score was reduced in patients with microalbuminuria compared to those without; 18 cpd (mean and 95% confidence intervals): [4.2 (3.8‐4.7) vs 5.0 (4.6‐5.4), p = 0.03]. Macular recovery performance was not significantly reduced: [21.0 arbitrary units (17.5–24.6) vs 26.0 (22.6–30.7), p = 0.12]. We conclude that impaired contrast sensitivity independent of background retinopathy is shown in a group of young Type 1 (insulin‐dependent) diabetic patients with low‐grade microalbuminuria compared to a group of patients with normoalbuminuria.
Red square test for visual field screening
Authors: Mandahl Agneta
Published: May 2009

Abstract. A reliable bedside test for screening of visual field defects is a valuable tool in the examination of patients with a putative disease affecting the sensory visual pathways. Conventional methods such as Donders' confrontation method, counting fingers in the visual field periphery, ot two‐hand confrontation are not sufficiently sensitive to detect minor but nevertheless serious visual field defects. More sensitive methods requiring only simple tools are also described. In this study, a test card with four red squares surrounding a fixation target, a black dot, with a total test area of about 11 times 12.5° at a distance of 30 cm, was designed for testing experience of red colour saturation in four quadrants, red square test. The Goldmann visual field was used as reference. 125 consecutive patients with pituitary adenoma (159 eyes), cranio‐pharyngeoma (9 eyes), meningeoma (21 eyes), vascular hemisphere lesion (40 eyes), hemisphere tumour (10 eyes) and hemisphere abscess (2 eyes) were examined. The Goldmann visual field and red square test were pathological in pituitary adenomas in 35%, in craniopharyngeomas in 44%, in meningeomas in 52% and in hemisphere tumours or abscess in 100% of the eyes. Among these, no false‐normal or false‐pathological tests were found. However, in vascular hemisphere disease the corresponding figures were Goldmann visual field 90% and red square test 85%. The 5% difference (4 eyes) was due to Goldmann visual field defects strictly peripheral to the central 15°. These defects were easily diagnosed with two‐hand confrontation and were due to anterior occipital lobe infarction. The red square test is a sensitive and quick method for visual field screening. And, hitherto it seems to be the most simple of reliable visual field screening bedside tests described.
The effect of brief intrascleral or episcleral application of mitomycin C on the ciliary epithelium and pressure in the rabbit eye
Authors: Holló Gábor , Süveges Ildikó
Published: May 2009

Abstract. Ten albino rabbits underwent bilateral Cairns' trabeculectomy (group 1). A sponge soaked with 0.5 mg/ml mitomycin C solution was applied under the scleral flap for 5 min followed by irrigation with 20 ml 0.9% sodium chloride solution in the left eyes. In the right eyes a sponge soaked with 0.9% sodium chloride solutions was applied. In 9 albino rabbits a 3 times 2 mm episcleral area at 12 o'clock position was exposed to 0.5 mg/ml mitomycin C solution on one side and to 0.9% sodium chloride solution in the contralateral eye (group 2). Five, 10 and 30 days (group 1 and 2) and 3 months (group 1) following surgery specimens of the ciliary body adjacent, beside and opposite to the site of the operation were excised and studied with light and electron microscopy. No stromal or epithelial morphological changes of toxic origin have been revealed in the ciliary processes, even in specimens adjacent to the surgical area. In 5 albino rabbits (group 3) intraocular pressure was recorded before surgery and 5, 10 and 30 days after unilateral, episcleral mitomycin C application described in group 2. No significant changes or interocular difference has been recorded. The results suggest that long‐term postoperative hypotony following trabeculectomy with mitomycin C is not caused by reduced aqueous humour secretion of toxic origin.
Retinal and optic disc neovascularization in leukaemia
Authors: Anderton L. , Amoaku W. M. K. , Noble B. A.
Published: May 2009

Abstract. We report a case of chronic myeloid leukaemia initially presenting with a vitreous haemorrhage associated with bilateral retinal and optic disc neovascularization. The literature is briefly reviewed and the probable reasons for the observed microcirculatory disturbances are discussed.
Optic nerve aplasia associated with macular ‘atypical coloboma’
Authors: Recupero Santi Maria , Lepore Giovanni Francesco , Plateroti Rocco , Abdolrahimzadeh Solmaz
Published: May 2009

Abstract. A 12‐year‐old patient presenting with absence of the optic disc and retinal blood vessels associated with atrophic macular lesion was studied. A toxoplasma IgG antibody test had been found positive at the age of 4 months. This test and the clinial findings suggested the possibility of optic nerve aplasia with atypical macular coloboma due to congenital toxoplasmosis. The pro's and contra's concerning this hypothesis are discussed by the authors.
Electrophysiological methods in early glaucoma detection
Authors: Fernández‐Tirado F. J. , Uclés P. , Pablo L. , Honrubia F. M.
Published: May 2009

Abstract Electrophysiological methods like pattern electroretinogram and pattern visual evoked potentials may be the best approach for early glaucoma detection, as they have demonstrated to be sensitive to the ganglion cells functional changes. Reported values of both P50 and N95 pattern electroretinogram components differ widely, a fact perhaps related to a heterogeneous grouping of patients suffering from ocular hypertension and glaucoma, rather than to the type of technique utilized. This study is based on a total of 42 subjects: 14 normals, 16 subjects suffering from ocular hypertension, and 12 patients with glaucoma, with 79 eyes examined. Pattern electroretinogram and pattern visual evoked potentials were used as successive techniques. Setting condition for pattern electroretinogram, such as low temporal frequency (2 Hz), 30 min check size, high contrast (99%) and luminance (93 cd/m2), identified the N95 component as the best index for early glaucoma detection. In the control group N95 mean amplitude was 1.62μV ± 0.59 SD and showed almost significant difference with ocular hypertension (p = 0.07) and highly significant difference with the glaucoma group (p < 0.01), with decrement of 58.6% in the glaucoma group. P50 mean amplitude, on the contrary, did not show significant differences among the groups (Newman‐Keul test), its reduction in glaucoma being 28%. The mean pattern visual evoked potentials latency was also highly significant between glaucoma and control groups, but not between ocular hypertension and control groups; the mean amplitude did not show significant differences. A proportion of 26.6% abnormal pattern electroretinogram was found in the group suspected of having glaucoma where conventional methods had proved normal. Pattern visual evoked potentials had a proportion of 23.3% abnormal values and must be regarded as a complementary test. This is most important from a clinical standpoint since a decision on treatment to prevent glaucoma and a strict control of the affected eyes have to be undertaken.
The effect of panretinal laser photocoagulation on visual acuity, visual fields and on subjective visual impairment in preproliferative and early proliferative diabetic retinopathy
Authors: Henricsson Marianne , Heijl Anders
Published: May 2009

Abstract The effect of panretinal laser scatter treatment on visual fields, visual acuity and subjective complaints was assessed in 11 patients with severe nonproliferative or early proliferative diabetic retinopathy. Patients were prospectively examined before and after panretinal treatment using automated static threshold perimetry with program 30‐2 on the Humphrey perimeter, and they were interviewed. Visual field sensitivity was often depressed even before treatment with mean MD – 4.3 (–1, ‐11.6) dB, but was significantly lower (p < 0.01, ANOVA) 2 weeks after treatment with mean MD – 8.6 dB. Visual fields remained stable 4 months later. Treatment increased the number of eyes with visual fields as defined by abnormal MD values at the p < 0.05 level from 8 to 16 among the 17 treated. In spite of considerable impairment of visual fields after treatment, subjective problems were small and the visual field impairment seemed to have little influence on everyday life.
Corneal sensation in insulin dependent and non‐insulin dependent diabetics with proliferative retinopathy
Authors: Ruben Simon T.
Published: May 2009

Abstract The corneal sensation of diabetic patients undergoing pan retinal photocoagulation for the treatment of proliferative retinopathy was measured using the Cochet‐Bonnet aesthesiometer. Insulin dependent and non‐insulin dependent diabetics both showed significantly decreased corneal sensitivity, and there was no significant change following pan‐retinal photocoagulation. Insulin dependent diabetics with proliferative retinopathy had been diagnosed for a significantly longer period than non‐insulin dependent diabetics, but had better corneal sensitivity than the latter group. Male patients were more likely to have brown irides, whereas there was a preponderance of blue irides amongst the females. Patients with blue irides also had significantly lower sensitivity than patients with brown irides. The results are discussed.
The shape of the corneal apical zone after excimer photorefractive keratectomy
Authors: Patel S. , Marshall J. , Fitzke F. W. , Gartry D. S.
Published: May 2009

Abstract Applying an experimental photo‐keratoscope, which assesses the shape of cornea within the pupillary region, to a group of subjects who have undergone excimer laser photorefractive keratectomy over a central 4 mm chord diameter of the cornea, we report the shape of the typical cornea within the ablated zone conforms to a steepening ellipse (average shape factor, 1.25). A statistically significant difference in the mean shape factor (asphericity) between the photoablated and the normal cornea (average shape factor 0.89) was not confirmed. However, there is more variability in the shape factors found in the photorefractive keratectomy group compared with normals, within the same distance from the corneal apex. Using the criterion of overlap within two standard deviations, averaging the vertical horizontal meridians, 75% of photorefractive keratectomy eyes fall within the shape factor limits of the normal eye group. In all cases the post‐ablated corneal surface was found to be regular in terms of surface quality alone. The excimer photorefractive keratectomy technique is therefore a clinically acceptable method of refractive surgery.
Senile and presenile cataract
Authors: Lesiewska‐Junk Hanna
Published: May 2009

Abstract Two groups of patients operated on because of cataract were compared: 106 patients from Poland and 103 patients from Norway. Mean age in the Polish group was 60 years and in the Norwegian 76 years. To explain the difference in age at operation the incidence of some cataract risk factors ‐ diabetes, myopia, rural residence, outdoor occupation, cataract in family, steroid therapy, smoking and alcohol intake ‐ were evaluated. Significant differences between these two groups were found only for rural residence, alcohol intake and cigarette smoking. The author suggests another possible factor causing earlier cataract formation among Polish patients.
Central retinal artery occlusion in a patient with Fabry's disease documented by scanning laser ophthalmoscopy
Authors: Andersen Mads Varis Nis , Dahl Helena , Fledelius Hans , Nielsen Niels Vesti
Published: May 2009

Abstract Fabry's disease, angiokeratoma corporis diffusum, is an X‐linked inborn error of glycosphingolipid metabolism due to lack of activity of the lysosomal enzyme, alpha‐galactosidase A, resulting in progressive intracellular deposition of neutral glycosphingolipids in various tissues, including vascular endothelial ‐ and smooth muscle cells. Occlusions of the retinal vessels are rare. We present a case of central retinal artery occlusion in a 25‐year‐old male with Fabry's disease, documented by fluorescein‐ and indocyanine green angiography performed by scanning laser opththalmoscopy.
Immunogenicity and Safety of Recombinant Rabies Viruses Used for Oral Vaccination of Stray Dogs and Wildlife
Authors: Faber M. , Dietzschold B. , Li J.
Published: May 2009

Rabies is a zoonotic disease and stray dogs, wild carnivores and bats are the natural reservoirs of rabies. Oral immunization with live vaccines is the only practical approach to eradicate rabies in free ranging terrestrial animals. We have developed the double glycoprotein (G) rabies virus (RV) variant SPBNGAS‐GAS that has great promise to be used as a live‐attenuated vaccine. Oral immunization of rodents and several target animal species with this double G RV variant resulted in the induction of protective immunity, superior to that induced by a single RV G variant (SPBNGAS). The high oral efficacy of SPBNGAS‐GAS is likely because of its increased ability to infect monocytes or immature dendritic cells (DCs), thereby inducing their conversion into mature DCs. Furthermore, infection of DCs with the double G variant resulted in a strong up‐regulation of the expression of genes related to the NFκB signalling pathway including IFN‐α and IFN‐β, which might underlie the protection conferred by this live RV vaccine. A potential problem associated with the use of live RVs for oral vaccination could rest in the possibility of reversion to the pathogenic phenotype because of the high mutation rate characteristic for all RNA viruses. In this respect, the presence of a second non‐pathogenic G gene decreases considerably the risk of reversion to the pathogenic phenotype because a non‐pathogenic G is dominant over a pathogenic G in determining the pathogenicity of the double G RV variant. Because of its excellent efficacy and safety, the SPBNGAS‐GAS vaccine may provide a distinct advantage over other live RV vaccine in its ability to vaccinate a broad range of mammalian species.
Serum Nucleic Acids in an Experimental Bovine Transmissible Spongiform Encephalopathy Model
Authors: Beck Julia , Urnovitz Howard B. , Groschup Martin H. , Ziegler Ute , Brenig Bertram , Schütz Ekkehard
Published: May 2009

Repetitive genomic nucleic acid sequences (RGNASs) have been detected in serum samples from both PrPres confirmed cows and cohorts and unexposed cattle. These RGNASs have polymorphisms that can be candidates for detecting subclinical disease processes. To confirm the presence of serum RGNAS polymorphisms in bovine spongiform encephalopathy (BSE), samples were obtained from an experimental study whereby cows were inoculated orally with BSE‐infectious or control brain material. Fleckvieh/Brown Swiss cattle were fed 100 g of either PrPres‐positive brain stem macerate or normal brain material (controls). Serum samples were taken 40 months post‐inoculation (15 infected, 6 control non‐infected and 5 randomly selected normal animals). Approximately, 6e5 sequences were analysed and the results showed that serum RGNAS polymorphisms could be detected in all of the infected animals but not in the control animals. In addition, polymorphisms in serum non‐RGNASs were detected in BSE‐infected animals that differed significantly from the controls (P < 0.01). These data reveal the complexity of serum nucleic acid sequences that can be detected in 200 μl of serum and further add to the guidelines for using serum nucleic acids in diagnostics. In conclusion, RGNAS polymorphism detection may have general applications for the study of other emerging zoonoses.
Rabies in the Face of the 21st Century
Authors: Koprowski H.
Published: May 2009

Reference to an ancient Hindu picture of a snarling dog may be a convincing enough proof to consider the fact that rabies has been known in the world for the past 50 centuries. Prior to the monumental observation about rabies of Fracastoro in the 16th century, facts and fantasies were intermingled in the study of rabies. In the realm of fantasy, consider the statement of Aristotle (otherwise a great philosopher) that only animals and not humans die of rabies. It took 19 centuries before Fracastoro finally established that infection with rabies is lethal for all warm‐blooded beings including humans. The new era of rabies dates from the time of Galtier who isolated the virus and Pasteur who was able to create a somewhat attenuated strain of virus fixe which became the tool of laboratory studies for many decades after Pasteur. During the last 50 years of the past century, our knowledge of rabies increased by leaps and bounds. First of all, using molecular biology as a tool, it was possible to ‘take the virus apart’, so to speak and describe and analyse all of its components. Establishment of multivariability among viruses as ‘de la rue’ permitted not only a construct of a genetic linkage among lyssa family but also solved some puzzles of pathogenesis of rabies which defied solution when all work concentrated on one laboratory strain of the virus. As an example, we know much more now about the genetic background regulating virulence of the virus. In addition, it is now possible to use rabies as a vector of biological materials such as vaccines or sera. There is no progress in the treatment of the uniformly lethal disease. Perhaps, optimistically speaking, the 21st century will bring us a glimmer of hope for the successful treatment of human rabies.
Changing Ideals in a Donor Organisation: ‘Participation’ in Sida
Authors: Cornwall Andrea
Published: May 2009

Development buzzwords shelter diverse and often divergent strands of meaning and practice, lending an air of credibility and currency to the policies of the agencies that espouse them. Tracing the trajectory of one of these buzzwords, ‘participation’, in Swedish development cooperation, this paper seeks to unpack some of those diverse meanings and lend form to some of those divergent practices. It weaves together institutional ethnography with oral history and textual analysis, fortified by insights from a unique action research initiative on participation. This innovative process brought together desk officers from across the institution in a participatory learning group that met for the best part of a year to explore the challenge of institutionalising participation in Sida.

The paper tells the tale of efforts to promote and negotiate participation in a changing external and institutional environment. It begins in a time when the term had not yet gained currency but in which the practice of Swedish development cooperation resonated with many of the ideals that were associated with popular participation. It goes on to chart the rise of ‘popular participation’ (folkligt deltagende) and other variants, community participation, beneficiary participation, stakeholder participation and civil society participation, as Swedish development cooperation came to be influenced by the discourses and practices of bilateral and multilateral development institutions. Pursuing the trajectory of participation into an era in which other buzzwords – harmonisation, ownership and account‐ability – have taken precedence, it reflects on the paradoxes of efforts to institutionalise ideals within development bureaucracies as they grapple with the opportunities, challenges and contradictions of the Paris Agenda and the reconfiguration of the business of aid.
Citrobacter rodentium colitis evokes post‐infectious hyperexcitability of mouse nociceptive colonic dorsal root ganglion neurons
Authors: Ibeakanma Charles , Miranda‐Morales Marcela , Richards Michele , Bautista‐Cruz Francisco , Martin Nancy , Hurlbut David , Vanner Stephen
Published: May 2009

To investigate the possible contribution of peripheral sensory mechanisms to abdominal pain following infectious colitis, we examined whether the Citrobacter rodentium mouse model of human E. coli infection caused hyperexcitability of nociceptive colonic dorsal root ganglion (DRG) neurons and whether these changes persisted following recovery from infection. Mice were gavaged with C. rodentium or distilled water. Perforated patch clamp recordings were obtained from acutely dissociated Fast Blue labelled colonic DRG neurons and afferent nerve recordings were obtained from colonic afferents during ramp colonic distensions. Recordings were obtained on day 10 (acute infection) and day 30 (infection resolved). Following gavage, colonic weights, myeloperoxidase (MPO) activity, stool cultures, and histological scoring established that infection caused colitis at day 10 which resolved by day 30 in most tissues. Electrophysiological recordings at day 10 demonstrated hyperexcitability of colonic DRG neurons (40% mean decrease in rheobase, P= 0.02; 50% mean increase in action potential discharge at twice rheobase, P= 0.02). At day 30, the increase in action potential discharge persisted (∼150% increase versus control; P= 0.04). In voltage clamp studies, transient outward (IA) and delayed rectifier (IK) currents were suppressed at day 10 and IA currents remained suppressed at day 30. Colonic afferent nerve recordings during colonic distension demonstrated enhanced firing at day 30 in infected animals. These studies demonstrate that acute infectious colitis evokes hyperexcitability of colonic DRG neurons which persists following resolution of the infection and that suppression of IA currents may play a role. Together, these findings suggest that peripheral pain mechanisms could contribute to post‐infectious symptoms in conditions such as post‐infectious irritable bowel syndrome.
Regulation of visceral adipose tissue‐derived serine protease inhibitor by nutritional status, metformin, gender and pituitary factors in rat white adipose tissue
Authors: González C. R. , Caminos J. E. , Vázquez M. J. , Garcés M. F. , Cepeda L. A. , Ángel A. , González A. C. , García‐Rendueles M. E. , Sangiao‐Alvarellos S. , López M. , Bravo S. B. , Nogueiras R. , Diéguez C.
Published: May 2009

Visceral adipose tissue‐derived serine protease inhibitor (vaspin) is a recently discovered adipocytokine mainly secreted from visceral adipose tissue, which plays a main role in insulin sensitivity. In this study, we have investigated the regulation of vaspin gene expression in rat white adipose tissue (WAT) in different physiological (nutritional status, pregnancy, age and gender) and pathophysiological (gonadectomy, thyroid status and growth hormone deficiency) settings known to be associated with energy homeostasis and alterations in insulin sensitivity. We have determined vaspin gene expression by real‐time PCR. Vaspin was decreased after fasting and its levels were partially recovered after leptin treatment. Chronic treatment with metformin increased vaspin gene expression. Vaspin mRNA expression reached the highest peak at 45 days in both sexes after birth and its expression was higher in females than males, but its levels did not change throughout pregnancy. Finally, decreased levels of growth hormone and thyroid hormones suppressed vaspin expression. These findings suggest that WAT vaspin mRNA expression is regulated by nutritional status, and leptin seems to be the nutrient signal responsible for those changes. Vaspin is influenced by age and gender, and its expression is increased after treatment with insulin sensitizers. Finally, alterations in pituitary functions modify vaspin levels. Understanding the molecular mechanisms regulating vaspin will provide new insights into the pathogenesis of the metabolic syndrome.
MurF Inhibitors with Antibacterial Activity: Effect on Muropeptide Levels
Authors: Baum Ellen Z. , Crespo-Carbone Steven M. , Foleno Barbara D. , Simon Lee D. , Guillemont Jerome , Macielag Mark , Bush Karen
Published: May 2009

MurF catalyzes the last cytoplasmic step of bacterial cell wall synthesis and is essential for bacterial survival. Our previous studies used a pharmacophore model of a MurF inhibitor to identify additional inhibitors with improved properties. We now present the characterization of two such inhibitors, the diarylquinolines DQ1 and DQ2. DQ1 inhibited
Escherichia coli
MurF (50% inhibitory concentration, 24 μM) and had modest activity (MICs, 8 to 16 μg/ml) against lipopolysaccharide (LPS)-defective
E. coli
and wild-type
E. coli
rendered permeable with polymyxin B nonapeptide. DQ2 additionally displayed activity against gram-positive bacteria (MICs, 8 to 16 μg/ml), including methicillin (meticillin)-susceptible and -resistant
Staphylococcus aureus
isolates and vancomycin-susceptible and -resistant
Enterococcus faecalis
and
Enterococcus faecium
isolates. Treatment of LPS-defective
E. coli
cells with ≥2× MIC of DQ1 resulted in a 75-fold-greater accumulation of the MurF substrate compared to the control, a 70% decline in the amount of the MurF product, and eventual cell lysis, consistent with the inhibition of MurF within bacteria. DQ2 treatment of
S. aureus
resulted in similar effects on the MurF substrate and product quantities. At lower levels of DQ1 (≤1× MIC), the level of accumulation of the substrate was less pronounced (15-fold greater compared to the amount for the control). However, a 50% increase in the amount of the MurF product compared to the control was reproducibly observed, consistent with the possible upregulation of muropeptide biosynthesis upon partial inhibition of this pathway. The overexpression of cloned MurF appeared to partly alleviate the DQ1-mediated inhibition of muropeptide synthesis. The identification of MurF inhibitors such as DQ1 and DQ2 that disrupt cell wall biosynthesis suggests that MurF remains a viable target for an antibacterial agent.
Three-Dimensional Model of Lanosterol 14α-Demethylase from
Cryptococcus neoformans
: Active-Site Characterization and Insights into Azole Binding
Authors: Sheng Chunquan , Miao Zhenyuan , Ji Haitao , Yao Jianzhong , Wang Wenya , Che Xiaoying , Dong Guoqiang , Lü Jiaguo , Guo Wei , Zhang Wannian
Published: May 2009

Cryptococcus neoformans
is one of the most important causes of life-threatening fungal infections in immunocompromised patients. Lanosterol 14α-demethylase (CYP51) is the target of azole antifungal agents. This study describes, for the first time, the 3-dimensional model of CYP51 from
Cryptococcus neoformans
(CnCYP51). The model was further refined by energy minimization and molecular-dynamics simulations. The active site of CnCYP51 was well characterized by multiple-copy simultaneous-search calculations, and four functional regions important for rational drug design were identified. The mode of binding of the natural substrate and azole antifungal agents with CnCYP51 was identified by flexible molecular docking. A G484S substitution mechanism for azole resistance in CnCYP51, which might be important for the conformation of the heme environment, is suggested.
UropathogenicEscherichia coli-Induced Inflammation Alters Mouse Urinary Bladder Contraction via an Interleukin-6-Activated Inducible Nitric Oxide Synthase-Related Pathway
Authors: Weng Te I. , Wu Hsiao Yi , Lin Pei Ying , Liu Shing Hwa
Published: May 2009

Escherichia coliis the most common cause of urinary tract infection. Elevated blood and urine interleukin-6 (IL-6) levels have been shown in inflammatory urinary tract diseases. The role of IL-6 in mediating the urodynamic dysfunction in response toE. coli-induced urinary tract infection has not yet been fully elucidated. In this study, we investigated the role of IL-6 in the nitric oxide (NO)-triggered alteration of contractile responses in the urinary bladder under anE. coli-induced inflammatory condition. The electrical field stimulation (EFS)-evoked contractions of the isolated detrusor strips, and immunoblotting for detecting protein expression in the bladders was measured short term (1 h) or long term (6 or 24 h) after intraperitoneal injection ofE. coliendotoxin (lipopolysaccharide [LPS]) or intravesical instillation of human pyelonephritogenicE. coli-J96 (O4:K6) strain or LPS into mice. IL-6 and NO productions were increased in the urinary bladders of mice 1 to 24 h after LPS orE. coli-J96 treatment. Inducible NO synthase (iNOS) expression and protein kinase C (PKC) activation and EFS-evoked detrusor contractions were increased in the bladders at 6 h after LPS orE. coli-J96 treatment, which could be reversed by anti-IL-6 antibody and iNOS inhibitor aminoguanidine. At 1 h after LPS administration, bladder NO generation, endothelial NOS expression, and EFS-evoked detrusor contractions were effectively increased, whereas anti-IL-6 antibody could not reverse these LPS-induced responses. These results indicate that IL-6 may play an important role in the iNOS/NO-triggered PKC-activated contractile response in urinary bladder duringE. colior LPS-induced inflammation.
Mycobacterium tuberculosisCpn60.2 and DnaK Are Located on the Bacterial Surface, Where Cpn60.2 Facilitates Efficient Bacterial Association with Macrophages
Authors: Hickey Tyler B. M. , Thorson Lisa M. , Speert David P. , Daffé Mamadou , Stokes Richard W.
Published: May 2009

Mycobacterium tuberculosis, the causative agent of tuberculosis, initially contacts host cells with elements of its outer cell wall, or capsule. We have shown that capsular material from the surface ofM. tuberculosiscompetitively inhibits the nonopsonic binding of wholeM. tuberculosisbacilli to macrophages in a dose-dependent manner that is not acting through a global inhibition of macrophage binding. We have further demonstrated that isolatedM. tuberculosiscapsular proteins mediate a major part of this inhibition. Two-dimensional polyacrylamide gel electrophoresis analysis of the capsular proteins showed the presence of a wide variety of protein species, including proportionately high levels of the Cpn60.2 (Hsp65, GroEL2) and DnaK (Hsp70) molecular chaperones. Both of these proteins were subsequently detected on the bacterial surface. To determine whether these molecular chaperones play a role in bacterial binding, recombinant Cpn60.2 and DnaK were tested for their ability to inhibit the association ofM. tuberculosisbacilli with macrophages. We found that recombinant Cpn60.2 can inhibit ∼57% of bacterial association with macrophages, while DnaK was not inhibitory at comparable concentrations. Additionally, when polyclonal F(ab′)2fragments of anti-Cpn60.2 and anti-DnaK were used to mask the surface presentation of these molecular chaperones, a binding reduction of ∼34% was seen for anti-Cpn60.2 F(ab′)2, while anti-DnaK F(ab′)2did not significantly reduce bacterial association with macrophages. Thus, our findings suggest that whileM. tuberculosisdisplays both surface-associated Cpn60.2 and DnaK, only Cpn60.2 demonstrates adhesin functionality with regard to macrophage interaction.
Strain and Virulence Diversity in the Mouse Pathogen
Chlamydia muridarum
Authors: Ramsey Kyle H. , Sigar Ira M. , Schripsema Justin H. , Denman Cecele J. , Bowlin Anne K. , Myers Garry A. S. , Rank Roger G.
Published: May 2009

The mouse chlamydial pathogen
Chlamydia muridarum
has been used as a model organism for the study of human
Chlamydia trachomatis
urogenital and respiratory tract infections. To date, two commonly used
C. muridarum
isolates have been used interchangeably and are essentially taken to be identical. Herein, we present data that indicate that this is not the case. The
C. muridarum
Weiss isolate and
C. muridarum
Nigg isolate varied significantly in their virulences in vivo and possessed different growth characteristics in vitro. Distinct differences were observed in intravaginal 50% infectious doses and in challenge infections, with the Weiss isolate displaying greater virulence. Respiratory infection by the intranasal route also indicated a greater virulence of the Weiss isolate. In vitro, morphometric analysis revealed that the Weiss isolate produced consistently smaller inclusions in human cervical adenocarcinoma cells (HeLa 229) and smaller plaques in monolayers of mouse fibroblasts (L929) than did the Nigg isolate. In addition, the Weiss isolate possessed significantly higher replicative yields in vitro than did the Nigg isolate. In plaque-purified isolates derived from our stocks of these two strains, total genomic sequencing identified several unique nonsynonymous single nucleotide polymorphisms and insertion/deletion mutations when our Weiss (
n
= 4) and Nigg (
n
= 5) isolates were compared with the published Nigg sequence. In addition, the two isolates shared 11 mutations compared to the published Nigg sequence. These results prove that there is genotypic and virulence diversity among
C. muridarum
isolates. These findings can be exploited to determine factors related to chlamydial virulence and immunity.
Establishment of an Adult Mouse Model for Direct Evaluation of the Efficacy of Vaccines against
Vibrio cholerae
Authors: Nygren E. , Li B.-L. , Holmgren J. , Attridge S. R.
Published: May 2009

We describe here a new animal model that offers the prospect of using conventional adult mice for direct evaluation of the protective potential of new cholera vaccines. Pretreatment of adult mice with oral streptomycin allowed intestinal colonization by streptomycin-resistant
Vibrio cholerae
strains of either the O1 or the O139 serogroup. Bacteria were recovered in greatest numbers from the cecum and large intestine, but recoveries from all regions of the gut correlated significantly with bacterial excretion in fresh fecal pellets, which thus provides a convenient indicator of the extent and duration of gut colonization. Mice immunized mucosally or systemically with viable or inactivated
V. cholerae
were shown to be comparatively refractory to colonization after challenge with the immunizing strain. Several variables were examined to optimize the model, the most significant being the size of the challenge inoculum; surprisingly, a smaller challenge dose resulted in more consistent and sustained colonization. Studies with mutant strains unable to produce cholera toxin or toxin-coregulated pili revealed that neither factor contributed significantly to colonization potential. Protection against
V. cholerae
challenge was shown to be serogroup restricted, and significant inverse correlations were detected between serum and intestinal anti-lipopolysaccharide antibody responses and the levels of excretion of challenge organisms.
Adenofibroma of the testis
Authors: Gatt N , Attard J , Degaetano J
Published: May 2009

Adenofibromas of the testicular parenchyma are exceptional with only one case published in the literature. Whereas adenofibromas of mullerian derivatives are well described, testicular tumours resembling surface ovarian epithelium are rare. We describe a case of adenofibroma discovered incidentally while investigating for a hydrocoele in a 57-year-old patient. Histological and immunohistochemical evaluation confirmed the lesion as being a serous adenofibroma with immunohistochemical properties analogous to its ovarian counterpart. These lesions are to be considered in the differential diagnosis of unusual cystic lesions of the testis, in order not to confuse it with more sinister pathology.
Road traffic accident fatalities: 1961 to 1986
Authors: Parry W R
Published: May 2009

The various trauma-induced pathologies found at necropsy following road traffic accidents in the Bassetlaw area of Nottinghamshire from 1961 to 1986 were recorded and related to the time of death. The catchment area was mainly rural, including stretches of the A1 and A57, but included two small towns (Worksop and Retford). Pick up times varied considerably depending on the site of the accident, extraction procedures and ambulance journey distance.
Dynamics of β-cell turnover: evidence for β-cell turnover and regeneration from sources of β-cells other than β-cell replication in the HIP rat
Authors: Manesso Erica , Toffolo Gianna M. , Saisho Yoshifumi , Butler Alexandra E. , Matveyenko Aleksey V. , Cobelli Claudio , Butler Peter C.
Published: May 2009

Type 2 diabetes is characterized by hyperglycemia, a deficit in β-cells, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). These characteristics are recapitulated in the human IAPP transgenic (HIP) rat. We developed a mathematical model to quantify β-cell turnover and applied it to nondiabetic wild type (WT) vs. HIP rats from age 2 days to 10 mo to establish 1) whether β-cell formation is derived exclusively from β-cell replication, or whether other sources of β-cells (OSB) are present, and 2) to what extent, if any, there is attempted β-cell regeneration in the HIP rat and if this is through β-cell replication or OSB. We conclude that formation and maintenance of adult β-cells depends largely (∼80%) on formation of β-cells independent from β-cell duplication. Moreover, this source adaptively increases in the HIP rat, implying attempted β-cell regeneration that substantially slows loss of β-cell mass.
Oral Midazolam Premedication for Children Undergoing General Anaesthesia for Dental Care
Authors: Sheta Saad A. , AlSarheed Maha
Published: May 2009

Objectives. To assess the efficacy and safety of injectable midazolam administered orally in 3 different doses in children undergoing complete dental rehabilitation under GA.Subjects and Methods. 60 children aged 2–6 years were enrolled in the study. The children were randomly assigned to one of 3 groups and received orally 0.5, 0.75, or 1.0 mg/kg of injectable midazolam mixed with apple juice 30 minutes before separation from parents. The following measurements were assessed: patient's acceptance of the medication, reaction to separation from parents, sedation scores, and recovery conditions.Results. More children were comfortable with parent separation in the group that received the 1.0 mg/kg dose (90%) compared to the group that received the 0.75 mg/kg dose (75%) and the group that received the 0.5 mg/kg dose (55%). The number of children who had desirable sedation was similar in the 0.75 mg/kg and 1.0 mg/kg dose groups. Twenty five percent of the children in the group that received the 0.5 mg/kg dose did not allow venepuncture before induction of GA, and induction of GA was poor for 20% of the children in this group. An increasing number of children scored excellent in terms of ease of venepuncture in 0.75 mg/kg dose group (10%) and in the 1.0 mg/kg dose group (20%) and in terms of induction of GA, 25% and 35%, respectively. Recovery of spontaneous ventilation and extubation was delayed by over 15 minutes in 2 children in the 1.0 mg/kg dose group.Conclusion. The dose of 0.75 mg/kg of injectable midazolam given orally as premedication is acceptable, effective, and safe.
H‐Darrieus Wind Turbine with Blade Pitch Control
Authors: Paraschivoiu I. , Trifu O. , Saeed F.
Published: May 2009

A procedure for computing the optimal variation of the blades′ pitch angle of an H‐Darrieus wind turbine that maximizes its torque at given operational conditions is proposed and presented along with the results obtained on a 7 kW prototype. The CARDAAV code, based on the “Double‐Multiple Streamtube” model developed by the first author, is used to determine the performances of the straight‐bladed vertical axis wind turbine. This was coupled with a genetic algorithm optimizer. The azimuthal variation of the blades′ pitch angle is modeled with an analytical function whose coefficients are used as variables in the optimization process. Two types of variations were considered for the pitch angle: a simple sinusoidal one and one which is more general, relating closely the blades′ pitch to the local flow conditions along their circular path. A gain of almost 30% in the annual energy production was obtained with the polynomial optimal pitch control.
Slope Stability and Slope Formation in the Flysch Zone of the Vienna Forest (Austria)
Authors: Terhorst Birgit , Damm Bodo
Published: May 2009

The Rhenodanubian Flysch of the northern Vienna Forest is composed of various layers of sandstones, marly shales, calcareous marls, and clay shists, which are covered by Quaternary periglacial cover beds and loess deposits. This area at the margin of the eastern Alps represents an undulating landscape of the Austrian low-mountain regions. The Vienna Forest Flysch region is considered to be susceptible to landslides. Both petrography of the bedrock and soil mechanical properties of the Quaternary sediments control the current slope dynamics in the study area. In a temporal context it is evident that the stability of slopes exceeding27∘is controlled by a succession of several steps of slope formation. On the basis of field surveys, laboratory analyses, and slope stability modelling, results from investigations on recent landslides demonstrate five different phases of slope formation. In general, after passing these phases the stability of studied slopes is increased, due to the different soil mechanical properties of the potential sliding masses.
Histopathological Diagnostic Discrepancies in Soft Tissue Tumours Referred to a Specialist Centre
Authors: Thway Khin , Fisher Cyril
Published: May 2009

Aims. A study was performed to determine areas of diagnostic discrepancy in the reporting of cases of soft tissue tumours referred to a specialist sarcoma unit. This was to pinpoint common discrepancies and to determine their causes.Methods and Results. We compared the sarcoma unit's histopathology reports with referring reports on 349 specimens from 277 patients with suspected or proven soft tissue tumours in a one-year period.Conclusions. Diagnostic agreement was found in 256 of 349 cases (73.4%), with minor diagnostic discrepancy in 55 cases (15.7%) and major discrepancy in 38 cases (10.9%). Benign/malignant discordances accounted for only 5% of all discrepancies (5 cases). The most common discrepancies occurred in tumour classification, including diagnosis of gastrointestinal stromal tumour and leiomyosarcoma and the subtyping of spindle cell sarcomas, as well as in tumour grading that could conceivably lead to changes in clinical management. Major diagnostic discrepancies leading to management change occurred in a relatively select range of tumour groups, and almost all discrepancies occurred due to differences in tumour interpretation between general or nonsoft tissue pathologists, and pathologists at the specialist unit. The findings support guidelines by the National Institute for Health and Clinical Excellence that diagnostic review of soft tissue tumours should be performed by specialist soft tissue pathologists.
Optimum Combination of Insulin-Transferrin-Selenium and Fetal Bovine Serum for Culture of Rabbit Articular Chondrocytes in Three-Dimensional Alginate Scaffolds
Authors: Zhang Lanlan , Song Hong , Zhao Xiaojun
Published: May 2009

Fetal bovine serum (FBS) has been reported to affect chondrocyte biosynthesis in monolayer culture. Insulin-Transferrin-Selenium (ITS) was investigated as a partial replacement for FBS during in vitro culture of rabbit articular chondrocytes in three-dimensional alginate scaffold. Chondrocyte-seeded alginate hydrogels were cultured in Dulbecco's modified Eagle's medium plus 10% FBS, 1% ITS plus 2% FBS, 1% ITS plus 4% FBS, or 1% ITS plus 8% FBS. At designed time point, the Chondrocyte-seeded alginate hydrogels were harvested and evaluated with histological staining, immunohistochemistry, and quantitative gene expression analysis. Viable cell density and cell division were also evaluated. Chondrocytes biosynthesis and cell division in 1% ITS with 2% FBS medium were similar to that in medium added with 10% FBS. For a total culture of 3 weeks, phenotypic gene expression in chondrocyte-seeded hydrogels was maintained at high levels in medium with 1% ITS plus 2% FBS, while it was decreased to varying degrees in the other groups. In conclusion, with 1% ITS, medium with 2% FBS could promote chondrocyte biosynthesis and cell division, and prevented cell dedifferentiation in three-dimensional alginate scaffolds.
Activation of Rap1 Promotes Prostate Cancer Metastasis
Authors: Bailey Candice L. , Kelly Patrick , Casey Patrick J.
Published: May 2009

Elucidating the mechanisms of prostate cancer (CaP) survival and metastasis are critical to the discovery of novel therapeutic targets. The monomeric G protein Rap1 has been implicated in cancer tumorigenesis. Rap1 signals to pathways involved in cell adhesion, migration, and survival, suggesting Rap1 may promote several processes associated with cancer cell metastasis. Examination of CaP cell lines revealed cells with a high metastatic ability exhibited increased Rap1 activity and reduced expression of the negative regulator Rap1GAP. Rap1 can be further stimulated in these cells by stromal-derived factor (SDF-1), an agonist known to regulate tumor cell metastasis and tropism to bone. Activation of Rap1 increased CaP cell migration and invasion, and inhibition of Rap1A activity via RNAi-mediated knockdown or ectopic expression of Rap1GAP markedly impaired CaP cell migration and invasion. Additional studies implicate integrins α4, β3, and αvβ3 in the mechanism of Rap1-mediated CaP migration and invasion. Extending the effect of Rap1 activity in CaP metastasis in vivo, introduction of activated Rap1 into CaP cells dramatically enhanced the rate and incidence of CaP metastasis in a xenograft mouse model. These studies provide compelling evidence to support a role for aberrant Rap1 activation in CaP progression, and suggest that targeting Rap1 signaling could provide a means to control metastatic progression of this cancer. [Cancer Res 2009;69(12):4962–8]