bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response of lung γδ T cells to experimental sepsis in mice
Authors: Hirsh Mark , Dyugovskaya Larissa , Kaplan Viktoria , Krausz Michael M. 
Published: April 2004

Summaryγδ T cells link innate and adaptive immune systems and may regulate host defence. Their role in systemic inflammation induced by trauma or infection (sepsis) is still obscured. The present study was aimed to investigate functions of lung γδ T cells and their response to experimental sepsis. Mice were subjected to caecal ligation and puncture (CLP) to induce sepsis and acute lung injury (ALI), or to the sham operation. Animals were killed 1, 4, and 7 days postoperatively; lungs were examined by histology, and isolated cells were studied by flow cytometry. Absolute number of γδ T cells progressively increased in lungs during sepsis, and reached a seven‐fold increase at day 7 after CLP (3·84 ± 0·41 × 105/lung; P = 0·0002 versus sham). A cellular dysfunction was revealed one day after CLP, as manifested by low cytolytic activity (22·3 ± 7·1%; P < 0·05 versus sham), low interferon‐γ (IFN‐γ; 8·5 ± 2·5%; P < 0·05 versus control) and interleukin‐10 (IL‐10) expression, and high tumour necrosis factor‐α expression (19·5 ± 1·7%; P < 0·05 versus control). The restoration of cytotoxicity, and increase in IFN‐γ and IL‐10 expression was observed at day 7 of CLP‐induced sepsis. In summary, our results demonstrate significant progressive accumulation of γδ T cells in lungs during CLP‐induced ALI. The temporary functional suppression of lung γδ T cells found early after CLP may influence the outcome of sepsis, possibly being associated with uncontrolled inflammatory lung damage.
Type‐A CpG oligonucleotides activate exclusively porcine natural interferon‐producing cells to secrete interferon‐α, tumour necrosis factor‐α and interleukin‐12
Authors: Guzylack‐Piriou Laurence , Balmelli Carole , McCullough Kenneth C. , Summerfield Artur 
Published: April 2004

SummaryNatural interferon‐producing cells (NIPC), also referred to as immature plasmacytoid dendritic cells (PDC), constitute a small population of leucocytes secreting high levels of type I interferons in response to certain danger signals. Amongst these signals are those from DNA containing unmethylated CpG motifs. The present work demonstrated that the CpG oligonucleotides (CpG‐ODN) 2216, D32 and D19 induce high amounts of interferon‐α (IFN‐α), tumour‐necrosis factor‐α (TNF‐α) and interleukin (IL)‐12 in porcine peripheral blood mononuclear cells (PBMCs). Swine workshop cluster 3 (SWC3)1ow CD4high cells, with high IL‐3‐binding activity, representing NIPC, were the exclusive cytokine‐producing cells responding to the CpG‐ODN. These cells did not express CD6, CD8 or CD45RA. Importantly, monocyte‐derived DC did not respond to CpG‐ODN by secretion of IFN‐α or TNF‐α or by the up‐regulation of costimulatory molecule expression. CpG‐ODN up‐regulated MHC class II and CD80\86 expression on the NIPC, but were unable to promote NIPC survival. Interestingly, certain CpG‐ODN, incapable of inducing NIPC to secrete IFN‐α or up‐regulate MHC class II and CD80\86, did promote NIPC viability. Taken together, the influence of CpG‐ODN on porcine NIPC, monocytes and myeloid DCs relates to that observed with their human equivalents. These results represent an important basis for the application of CpG‐ODN as adjuvants for the formulation of novel vaccines and demonstrate the importance of the pig as an alternative animal model for this approach.
Effects of topical nipradilol and timolol maleate on intraocular pressure, facility of outflow, arterial blood pressure and pulse rate in dogs
Authors: Maehara S. , Ono K. , Ito N. , Tsuzuki K. , Seno T. , Yokoyama T. , Yamashita K. , Izumisawa Y. , Kotani T. 
Published: April 2004

AbstractNipradilol is an α1, β‐blocker with milder side effects than other β‐blockers used in humans. In this study the effects of nipradilol were compared with those of timolol maleate in dogs. Twelve clinically normal dogs (nine mongrels, two beagles, and one Akita) were used. We applied 0.25% nipradilol or 0.5% timolol maleate drops for a period of 28 days. Intraocular pressure (IOP) was measured before and after administration on the 2nd, 4th, 7th, 14th, 21st and 28th day. Blood pressure, pulse rate and coefficient of aqueous outflow (C‐value) were also measured before and after administration on the 7th, 14th, 21st and 28th day. Both nipradilol and timolol maleate significantly lowered IOP from the 2nd day to the end of the study period. Nipradilol lowered IOP to an equivalent degree to timolol maleate. There was no significant change in blood pressure and pulse rate throughout the study period with administration of nipradilol. C‐value showed a significant rise from the 14th day with administration of nipradilol, while it did not show any significant change during the study period with administration of timolol maleate. The reduction of IOP by nipradilol was similar to that by an existing β‐adrenergic antagonist, timolol maleate, but nipradilol was associated with fewer systemic side effects in dogs. Nipradilol appears to be a useful drug for treatment of glaucoma in dogs.
Indium‐111 labeled vitamin B12 imaging of a ciliary adenoma with concurrent grade 2 soft tissue sarcoma of the leg in a Labrador Retriever
Authors: Whittemore Jacqueline C. , Gionfriddo Juliet R. , Steyn Phillip F. , Ehrhart E. J. 
Published: April 2004

AbstractAn 11‐year‐old, male castrated, Labrador Retriever was evaluated for the presence of rapidly growing concurrent leg and intraocular masses. Metastasis was noted in the chest at time of initial presentation. Indium‐111 labeled vitamin B12 imaging was performed, and there was significant uptake by both primary tumors and the lung metastases. Enucleation and amputation were performed for palliative relief. The leg mass was a grade 2 soft tissue sarcoma and the ocular mass a ciliary adenoma. The dog remained symptom‐free for approximately 10 weeks before developing signs of respiratory distress. He was euthanized 12 weeks after initial presentation, and there was diffuse infiltration of the lungs with metastatic sarcoma. Indium‐111 labeled vitamin B12 imaging identified a ciliary adenoma in this case and may provide a useful differentiation technique for evaluation of intraocular and retrobulbar masses if it can be demonstrated that there is differential uptake between inflammatory or infectious conditions and neoplasia.
Inherited retinal dysplasia and persistent hyperplastic primary vitreous in Miniature Schnauzer dogs
Authors: Grahn Bruce H. , Storey Eric S. , McMillan Catherine 
Published: April 2004

AbstractThe objectives of this study were to define the clinical syndrome of retinal dysplasia and persistent primary vitreous in Miniature Schnauzer dogs and determine the etiology. We examined 106 Miniature Schnauzers using a biomicroscope and indirect ophthalmoscope. The anterior and posterior segments of affected dogs were photographed. Four enucleated eyes were examined using routine light microscopy and scanning electron microscopy. A pedigree was constructed and related dogs were test‐bred to define the mode of inheritance of this syndrome. Congenital retinal dysplasia was confirmed in 24 of 106 related Miniature Schnauzer dogs. Physical and postmortem examinations revealed that congenital abnormalities were limited to the eyes. Biomicroscopic, indirect ophthalmoscopic, and neuro‐ophthalmic examinations confirmed that some of these dogs were blind secondary to bilateral retinal dysplasia and detachment (nonattachment) (n = 13), and the remainder had generalized retinal dysplasia (n = 11). Fifteen of these dogs were also diagnosed with unilateral (n = 9) or bilateral (n = 6) persistent hyperplastic primary vitreous. Nutritional, infectious, or toxic etiologies were not evident on physical, postmortem, light microscopic, or transmitting and scanning electron microscopic examination of four affected Miniature Schnauzers. We examined the pedigree and determined that an autosomal recessive mode of inheritance was most likely. Three test‐bred litters including those from affected parents, carrier and affected parents, and carrier parents confirmed this mode of inheritance. This study confirms that retinal dysplasia and persistent hyperplastic primary vitreous is a congenital abnormality that is inherited as an autosomal recessive condition in Miniature Schnauzers.
Mycotic endophthalmitis in a dog caused byCandida albicans
Authors: Linek Jens 
Published: April 2004

AbstractA case of mycotic endophthalmitis in the dog caused byCandida albicansis presented. The 3‐year‐old dog had a history of bloody diarrhea 3 months previously. The dog presented with acute signs of unilateral panuveitis. Aqueocentesis, vitreocentesis, and routine blood tests were performed but did not contribute to the diagnosis. The posterior segment could not be visualized because of flare and fibrin. On day 7 ultrasonography showed retinal separation which progressed to vitreous compartmentalization and abscessation by day 14. Three weeks after onset, glaucoma developed and enucleation was performed. Histology revealed the yeastCandidato be the causative agent. Post‐enucleation serumCandidaantibody titer was 1 : 640 (human threshold 1 : 120), as determined by agglutination test. A relapse of enteric signs 3 months later led to the diagnosis of chronic lymphocytic enteritis. An hematogenous route of infection is suspected.
Normalization of lens protein kinase Cγ in galactosemic dogs by a novel aldose reductase inhibitor
Authors: Takemoto Dolores J. , Harris Richard , Brightman Al , McGill John , Hua Duy , Davidson Harriet , Fenwick Brad , Wagner Lynn M. 
Published: April 2004

AbstractThe purpose of this study was to determine the effects of a novel aldose reductase inhibitor on lens protein kinase Cγ (PKCγ) levels in galactosemic dogs. Six‐month old Beagles (12 total; 6 male and 6 female) were made galactosemic by feeding a diet of 40% galactose for 6 weeks. Three dogs per group were fed either control, normal diet, 40% galactose diet, 40% galactose diet with aldose reductase inhibitor at 100 mg/kg body weight per day given orally, or a control diet with aldose reductase inhibitor alone (1‐H,7‐H‐5α,6,8,9‐tetrahydro‐1‐oxopyran[4,3‐β]1 benzopyran, referred to herein as HAR‐1). Lenses were removed and analyzed for toxicity by pathological examination. Lens polyol concentrations were determined by GC/MS. PKCγ levels were determined by Western blot and by reverse transcriptase‐polymerase chain reaction (RT‐PCR). No toxicity was observed from the aldose reductase inhibitor when given at 100 mg/kg body weight per day for 6 weeks. Galactosemic dogs showed deterioration of lens cells. Deterioration included vacuole formation in the lens, cell lysis, and loss of cell nuclei. Galactosemic dogs given the HAR‐1 appeared identical to control dogs. Polyol concentrations in the lenses were reduced by 50% in dogs fed the 40% galactose diet with the aldose reductase inhibitor, HAR‐1. PKCγ protein levels were reduced in the galactosemic dog lenses, but synthesis of PKCγ was not affected, as measured by RT‐PCR. The PKCγ protein levels were similar to controls in dogs given the aldose reductase inhibitor, HAR‐1, even when polyol concentrations remained 50% elevated above control levels. HAR‐1, when given to control dogs, caused a reduction in the synthesis of PKCγ mRNA but not in total PKCγ protein levels. This study demonstrates the use of a novel aldose reductase inhibitor to control changes in PKCγ in dog lens, a PKC that is known to control gap junction activity.
Ocular histopathologic observations in Norwegian Elkhounds with primary open‐angle, closed‐cleft glaucoma
Authors: Oshima Yoshie , Bjerkas Ellen , Peiffer Robert L. 
Published: April 2004

AbstractA retrospective histopathologic study of primary glaucoma in the Norwegian Elkhound was undertaken with the study of 9 clinically normal eyes and 22 glaucomatous eyes. All glaucomatous eyes showed goniodysgenesis as manifested by pectinate ligament dysplasia and/or trabecular meshwork dysplasia. Cystic degeneration of the iridociliary epithelial and/or peripheral retina was present in a high percentage of both normotensive and glaucomatous eyes. Utilizing the scheme proposed by Smithet al. (Veterinary and Comparative Ophthalmology1993;3: 16–28) the morphology of this disease in the Norwegian Elkhound would be classified as an open‐angle, closed‐cleft glaucoma, with histopathologic alterations of the outflow pathway similar to that described in other breeds with primary glaucoma.
A clinically orientated approach increases the efficiency of screening for latent autoimmune diabetes in adults (LADA) in a large clinic‐based cohort of patients with diabetes onset over 50 years
Authors: Monge L. , Bruno G. , Pinach S. , Grassi G. , Maghenzani G. , Dani F. , Pagano G. 
Published: April 2004

AbstractAims  To assess if a clinically orientated approach improves screening for latent autoimmune diabetes in adults (LADA) in patients developing diabetes over age 50.Methods  From a clinic‐based cohort of 3327 patients with Type 2 DM diagnosed over age 50 we recruited those with at least one feature suggestive of insulin deficiency: (i) fasting blood glucose ≥ 15 mmol/l and/or HbA1c ≥ 10% in spite of adequate compliance to diet and treatment; (ii) decreasing body weight ≥ 10% in the previous 3 months in spite of constant diet; (iii) BMI < 25 mg/kg2. A control group of 240 patients not presenting any of the previous criteria was randomly selected from the out‐patient clinic.Results  We identified 220 (6.6%) patients, of whom 70 were positive for glutamic acid decarboxylase antibodies (GADA) and/or islet cell antibodies (ICA), giving a prevalence of LADA of 31.8% (95% CI 25.7–38.4). In contrast, no patient randomly selected from the remaining cohort had marker positivities. With respect to patients negative for both ICA and GADA, those who were positive had lower C‐peptide values (0.53 ± 0.51 vs. 0.88 ± 0.42 nmol/l, P < 0.001); the lowest levels were found in patients in whom both antibodies were positive. In linear regression analysis, variables independently associated with fasting C‐peptide were GADA (β = −0.25, P < 0.001), ICA (β = −0.15, P = 0.04), BMI (β = 0.03, P < 0.001) and duration of diabetes (β = −0.02, P < 0.001).Conclusion  This study shows that: (i) a clinically orientated approach increases the efficiency of a screening programme for LADA, so that one in three screened patients are classified correctly; (ii) ICA and GADA positivity were negatively associated with residual β‐cell function, independent of BMI and duration of the disease; (iii) positivity for both ICA and GADA identifies patients with the lowest residual β‐cell function.
What is the relative contribution of blood glucose levels at different time points of the day to HbA1c in Type 1 diabetes?
Authors: Hillman N. , Herranz L. , Grande C. , Vaquero P. M. , Pallardo L. F. 
Published: April 2004

AbstractAims  To evaluate the relative contribution of blood glucose levels at different time points of the day to HbA1c in Type 1 diabetes.Methods  Consecutive home blood glucose records (n = 146) from 71 Type 1 diabetic patients who were on an intensive diabetes therapy programme were examined. Each home blood glucose record included six daily blood glucose profiles over 2 months. The relationship between glycaemic values at each time point and HbA1c measured at the end of each record period was analysed.Results  Significant linear correlations were found between HbA1c and glycaemia at each time point of the day (ranged from 0.413 to 0.593), the strongest being with predinner glycaemia (r = 0.593; P = 0.000). Total daily glycaemia, mean preprandial and mean postprandial glycaemia were also significant and linearly correlated with HbA1c (r = 0.701; r = 0.686; r = 0.620, respectively; P < 0.0001). Multiple linear regression analysis showed that predinner, prebreakfast and post‐breakfast glycaemia correlated significantly and independently with HbA1c. The model accounted for 47.8% of the variance in HbA1c.Conclusions  Our study shows that among individual time points, prebreakfast and predinner are those with more influence on HbA1c in Type 1 diabetes and, to a lesser extent, post breakfast. It also confirms that preprandial glycaemia better predicts overall glycaemic control in Type 1 diabetes than postprandial glycaemia.Diabet. Med. (2004)
Albuminuria in Afro‐Caribbeans with Type 2 diabetes mellitus: is the sickle cell trait a risk factor?
Authors: Oli J. M. , Watkins P. J. , Wild B. , Adegoke O. J. 
Published: April 2004

AbstractAims  To determine the prevalence of albuminuria [raised albumin–creatinine ratio (ACR)] in an out‐patient population of Afro‐Caribbeans with Type 2 diabetes mellitus (DM) and to determine if the possession of the sickle cell trait (SCT) is a risk factor.Patients and methods  The ACR in a morning urine sample was determined in each of 181 Afro‐Caribbeans with Type 2 DM attending the out‐patient clinic at King's Diabetes Centre of King's College Hospital, London. The subjects were genotyped for the SCT, Haemoglobin AS (HbAS).Results  Although a raised ACR was demonstrated more frequently in those with the SCT than in those without, with an odds ratio of 1.19, this was not statistically significant (P = 0.68).Conclusions  In this study the possession of the SCT does not appear to play a significant role in the development of albuminuria. However, a larger study is needed to clarify its role as a risk factor for development of albuminuria in Afro‐Caribbeans with Type 2 DM.
Regulation of a
Bacteroides
Operon That Controls Excision and Transfer of the Conjugative Transposon CTnDOT
Authors: Wang Yanping , Shoemaker Nadja B. , Salyers Abigail A. 
Published: April 2004

ABSTRACT

CTnDOT is a conjugative transposon (CTn) that is found in many
Bacteroides
strains. Transfer of CTnDOT is stimulated 100- to 1,000-fold if the cells are first exposed to tetracycline (TET). Both excision and transfer of CTnDOT are stimulated by TET. An operon that contains a TET resistance gene,
tetQ
, and two regulatory genes,
rteA
and
rteB
, is essential for control of excision and transfer functions. At first, it appeared that RteA and RteB, which are members of a two-component regulatory system, might be directly responsible for the TET effect. We show here, however, that neither RteA nor RteB affected expression of the operon. TetQ, a ribosome protection type of TET resistance protein, actually reduced operon expression, possibly by interacting with ribosomes that are translating the
tetQ
message. Fusions of
tetQ
with a reporter gene,
uidA
, were only expressed at a high level when the fusion was cloned in frame with the first six codons of
tetQ
. However, out of frame fusions or fusions ending at the other five codons of
tetQ
showed much lower expression of the
uidA
gene. Moreover, reverse transcription-PCR amplification of
tetQ
mRNA revealed that despite the fact that the
uidA
gene product, β-glucuronidase (GUS), was produced only when the cells were exposed to TET,
tetQ
mRNA was produced in both the presence and absence of TET. Computer analysis of the region upstream of the
tetQ
start codon predicted that the mRNA in this region could form a complex RNA hairpin structure that would prevent access of ribosomes to the ribosome binding site. Mutations that abolished base pairing in the stem that formed the base of this putative hairpin structure made GUS production as high in the absence of TET as in TET-stimulated cells. Compensatory mutations that restored the hairpin structure led to a return of regulated production of GUS. Thus, the
tetQ
-
rteA
-
rteB
operon appears to be regulated by a translational attenuation mechanism.
HybF, a Zinc-Containing Protein Involved in NiFe Hydrogenase Maturation
Authors: Blokesch Melanie , Rohrmoser Michaela , Rode Sabine , Böck August 
Published: April 2004

ABSTRACT

HypA and HypB are maturation proteins required for incorporation of nickel into the hydrogenase large subunit. To examine the functions of these proteins in nickel insertion, the
hybF
gene, which is a homolog of
hypA
essential for maturation of hydrogenases 1 and 2 from
Escherichia coli
, was overexpressed, and the product was purified. This protein behaves like a monomer in gel filtration and contains stoichiometric amounts of zinc but insignificant or undetectable amounts of nickel and iron. In filter binding assays radioactively labeled nickel binds to HybF with a

K
D

of 1.87 μM and in a stoichiometric ratio. To identify amino acid residues of HybF involved in nickel and/or zinc binding, variants in which conserved residues were replaced were studied. An H2Q replacement eliminated both in vivo activity and in vitro binding of nickel. The purified protein, however, contained zinc at the level characteristic of the wild-type protein. When E3 was replaced by Q, activity was retained, but an E3L exchange was detrimental. Replacement of each of the four conserved cysteine residues of a zinc finger motif reduced the cellular amount of HybF protein without a loss of in vivo activity, indicating that these residues play a purely structural role. A triple mutant deficient in the synthesis or activity of HypA, HybF, and HypB was constructed, and it exhibited the same responsiveness for phenotypic complementation by high nickel as mutants with a single lesion in one of the genes exhibited. The results are interpreted in terms of a concerted action of HypB and HybF in nickel insertion in which HybF (as well as its homolog, HypA) functions as a metallochaperone and HypB functions as a regulator that controls the interaction of HybF with the target protein.
Evolution of the Leucine Gene Cluster in
Buchnera aphidicola
: Insights from Chromosomal Versions of the Cluster
Authors: Sabater-Muñoz Beatriz , van Ham Roeland C. H. J. , Moya Andrés , Silva Francisco J. , Latorre Amparo 
Published: April 2004

ABSTRACT

In
Buchnera aphidicola
strains associated with the aphid subfamilies Thelaxinae, Lachninae, Pterocommatinae, and Aphidinae, the four leucine genes (
leuA
, -
B
, -
C
, and -
D
) are located on a plasmid. However, these genes are located on the main chromosome in
B. aphidicola
strains associated with the subfamilies Pemphiginae and Chaitophorinae. The sequence of the chromosomal fragment containing the leucine cluster and flanking genes has different positions in the chromosome in
B. aphidicola
strains associated with three tribes of the subfamily Pemphiginae and one tribe of the subfamily Chaitophorinae. Due to the extreme gene order conservation of the
B. aphidicola
genomes, the variability in the position of the leucine cluster in the chromosome may be interpreted as resulting from independent insertions from an ancestral plasmid-borne leucine gene. These findings do not support a chromosomal origin for the leucine genes in the ancestral
B. aphidicola
and do support a back transfer evolutionary scenario from a plasmid to the main chromosome.
Modulation of DNA Repair and Recombination by the Bacteriophage λ Orf Function inEscherichia coliK-12
Authors: Poteete Anthony R. 
Published: April 2004

ABSTRACTTheorfgene of bacteriophage λ, fused to a promoter, was placed in thegalKlocus ofEscherichia coliK-12. Orf was found to suppress the recombination deficiency and sensitivity to UV radiation of mutants, in a Δ(recC ptr recB recD)::Ptacgam bet exo pae cIΔrecGbackground, lackingrecF,recO,recR,ruvAB, andruvCfunctions. It also suppressed defects of these mutants in establishing replication of a pSC101-related plasmid. Compared toorf, therecA803allele had only small effects onrecF,recO, andrecRmutant phenotypes and no effect on aruvABmutant. In a fully wild-type background with respect to known recombination and repair functions,orfpartially suppressed the UV sensitivity ofruvABandruvCmutants.