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Comparison of the effectiveness of non-nucleoside reverse transcriptase inhibitor-containing and protease inhibitor-containing regimens using observational databases.

OBJECTIVES: To compare the effectiveness of first protease inhibitor (PI)-containing and non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: Data were analysed from three large HIV patient databases: Apache HIV Insight (APACHE), Target Management Services (TMS) and Clinical Partners (CP). The effectiveness of therapy was the time taken for HIV-1 RNA to fall below detectable levels on first highly active antiretroviral therapy regimen (PI- or NNRTI-containing) and the subsequent time to failure (two consecutive detectable measurements). Comparisons were made using proportional hazards models, adjusting for differences in age, sex, previous reverse transcriptase inhibitor use, calendar year and baseline viral load and CD4 T-cell count. RESULTS: The type of regimen was not associated with time to undetectable viral load in any of the three databases, all of which had high power to detect a difference. PI-containing regimens were significantly less likely to fail after reaching undetectable viral loads for APACHE and CP patients (relative hazard, 1.7; 95% confidence interval, 1.3--2.1 and relative hazard, 1.6; 95% confidence interval, 1.0--2.5 respectively). These results remained significant after allowing for an unmeasured confounder with moderate effect on risk. No significant association between time to failure and regimen was found for TMS patients, possibly due to low power (67% to detect a relative hazard of 1.5). No difference was found between regimens in the time taken for an increase of > 100 x 10(9)cells/l in CD4 T-cell count. In the APACHE database, those on NNRTI-containing regimens were more likely to have a failing CD4 T-cell response. CONCLUSIONS: PI-containing regimens have a lower risk of treatment failure than NNRTI-containing regimens.

Adult↗

Structure and synthesis of a lipid-containing bacteriophage. Effects of lipids containing cis or trans fatty acids on the reconstitution of bacteriophage PM2.

Infectious PM2 virus paticles could be reconstituted in vitro from a mixture of nucleocapsid, phospholipids containing cis fatty acids, and proteins I and II. The presence or absence of acyl phosphatidylglycerol, a minor lipid component of thevirion, did not affect the reconstitution of infectious particles, even though it was incorporated into the particles when present. When phosphatidylglycerol was completely replaced by acyl phosphatidylglycerol in the reconstitution mixture, no infections particles were formed. Lipids containing either cis or trans fatty acids were also used for reconstitution in vitro of the lipid-containing bacteriophage PM2. Regardless of the ratio of phosphatidlyglycerol to phospatidylethanolamine in the reconstitution mixture, infectious particles were formed and had almost the same phospholipid composition when lipids containing cis-palmitoleic acid were used; no infectious particles were obtained when lipids containing trans-palmitoleic acid were used. In the latter case, virus-like particles were, however, formed. Reconstituted particles containing cis fatty acids were infectious when tested on wild type Pseudomonas BAL-31 as well as on the unsaturated fatty acid auxotroph grown in the presence of either cis or trans-palmitoleic acid. Reconstituted particles containing trans fatty acids were not infectious on any of these cells. When trans fatty acids as well as cis fatty acids were present in the reconstitution mixture, then there was a lower yield of infectious particles. Particles with either cis or trans fatty acids had all four viral proteins and adsorbed to BAL-31 host cells in a specific manner.

Bacteriophages↗

HeLa cell cytoplasmic mRNA contains three classes of sequences: predominantly poly(A)-free, predominantly poly(A)-containing and bimorphic.

The mRNA species which exist in the HeLa cell polyribisomes in a form devoid of A sequences longer than 8 nucleotides constitute the poly(A)-free class of mRNA. The rapidly labelled component of this mRNA class shares no measurable sequence homology with poly(A)-containing RNA. If poly(A)-free mRNA larger than 12 S labelled for 2 h in vivo is hybridized with total cellular DNA, it hybridizes primarily with single-copy DNA. When a large excess of steady poly(A)-containing RNA is added before hybridization of labelled poly(A)-free RNA, no inhibition of hybridization occurs. This indicates the existence of a class of poly(A)-free mRNA with no poly(A)-containing counterpart. Some mRNA species can exist solely as poly(A)-containing mRNAs. These mRNAs in HeLa cells are found almost exclusively in the mRNA species present only a few times per cell (scarce sequences). Some mRNA species can exist in two forms, poly(A)containing and lacking, as evidenced by the translation data in vitro of Kaufmann et al. [Proc. Natl Acad. Sci. U.S.A. 74, 4801--4805 (1977)]. In addition, if cDNA to total poly(A)-containing mRNA is fractionated into abundant and scarce classes, 47% of the scarce class cDNA can be readily hybridized with poly(A)-free mRNA. 10% of the abundant cDNA to poly(A)-containing mRNA will hybridize with poly(A)-free sequences very rapidly while the other 90% hybridize 160 times more slowly, indicating two very different frequency distributions. The cytoplasmic metabolism of these three distinct mRNA classes is discussed.

Base Sequence↗

Cdc73p and Paf1p are found in a novel RNA polymerase II-containing complex distinct from the Srbp-containing holoenzyme.

The products of the yeast CDC73 and PAF1 genes were originally identified as RNA polymerase II-associated proteins. Paf1p is a nuclear protein important for cell growth and transcriptional regulation of a subset of yeast genes. In this study we demonstrate that the product of CDC73 is a nuclear protein that interacts directly with purified RNA polymerase II in vitro. Deletion of CDC73 confers a temperature-sensitive phenotype. Combination of the cdc73 mutation with the more severe paf1 mutation does not result in an enhanced phenotype, indicating that the two proteins may function in the same cellular processes. To determine the relationship between Cdc73p and Paf1p and the recently described holoenzyme form of RNA polymerase II, we created yeast strains containing glutathione S-transferase (GST)-tagged forms of CDC73, PAF1, and TFG2 functionally replacing the chromosomal copies of the genes. Isolation of GST-tagged Cdc73p and Paf1p complexes has revealed a unique form of RNA polymerase II that contains both Cdc73p and Paf1p but lacks the Srbps found in the holoenzyme. The Cdc73p-Paf1p-RNA polymerase II-containing complex also includes Gal11p, and the general initiation factors TFIIB and TFIIF, but lacks TBP, TFIIH, and transcription elongation factor TFIIS as well as the Srbps. The Srbp-containing holoenzyme does not include either Paf1p or Cdc73p, demonstrating that these two forms of RNA polymerase II are distinct. In confirmation of the hypothesis that the two forms coexist in yeast cells, we found that a TFIIF-containing complex isolated via the GST-tagged Tfg2p construct contains both (i) the Srbps and (ii) Cdc73p and Paf1p. The Srbps and Cdc73p-Paf1p therefore appear to define two complexes with partially redundant, essential functions in the yeast cell. Using the technique of differential display, we have identified several genes whose transcripts require Cdc73p and/or Paf1p for normal levels of expression. Our analysis suggests that there are multiple RNA polymerase II-containing complexes involved in the expression of different classes of protein-coding genes.

Amino Acid Sequence↗

Domains 17-27 of tropoelastin contain key regions of contact for coacervation and contain an unusual turn-containing crosslinking domain.

The central region of tropoelastin including domains 19-25 of human tropoelastin forms a hot-spot for contacts during the inter-molecular association of tropoelastin by coacervation [Wise, S.G., Mithieux, S.M., Raftery, M.J. and Weiss, A.S (2005). "Specificity in the coacervation of tropoelastin: solvent exposed lysines." Journal of Structural Biology 149: 273-81.]. We explored the physical properties of this central region using a sub-fragment bordered by domains 17-27 of human tropoelastin (SHEL 17-27) and identified the intra- and inter-molecular contacts it forms during coacervation. A homobifunctional amine reactive crosslinker (with a maximum reach of 11 A, corresponding to approximately 7 residues in an extended polypeptide chain) was used to capture these contacts and crosslinked regions were identified after protease cleavage and mass spectrometry (MS) with MS/MS verification. An intermolecular crosslink formed between the lysines at positions 353 of each strand of tropoelastin at the lowest of crosslinker concentrations and was observed in all samples tested, suggesting that this residue forms an important initial contact during coacervation. At higher crosslinker concentrations, residues K425 and K437 showed the highest levels of involvement in crosslinks. An intramolecular crosslink between these K425 and K437, separated by 11 residues, indicated that a structural bend must serve to bring these residues into close proximity. These studies were complemented by small angle X-ray scattering studies that confirmed a bend in this important subfragment of the tropoelastin molecule.

Amino Acid Sequence↗

Neuropeptide Y-containing neurons in the rat striatum: ultrastructure and cellular relations with tyrosine hydroxylase- containing terminals and with astrocytes.

The ultrastructural localization of neuropeptide Y (NPY) was comparatively examined in the dorsal (caudate-putamen) and ventral (nucleus accumbens) striatum using the peroxidase-antiperoxidase (PAP) method. In both striatal regions, NPY-like immunoreactivity (IR) was detected in perikarya, dendrites and axons. The labeled perikarya were 15-25 microns in a diameter and contained large, deeply and multiply indented nuclei and prominent Nissl bodies. The labeled dendrites contained a few large (80-150 nm) dense-core vesicles, lacked detectable spines and received few afferents. These morphological characteristics of NPY-IR neurons in both areas are in close accord with previous descriptions for the medium aspiny intrinsic neurons. Axon terminals with terminals with NPY-like IR contain primarily small clear round vesicles, as seen in single or serial sections. These terminals formed junctions that lacked recognizable pre- or post- synaptic densities, but showed parallel spacing between apposed plasmalemmas at presumed synaptic clefts. Targets of the axon terminals with NPY-like IR included unlabeled somata, unlabeled proximal dendrites and labeled and unlabeled distal dendrites. The NPY-IR neurons in the caudate-putamen differed from those in the nucleus accumbens in that (1) there were no recognized appositions between labeled dendrites and labeled terminals, and (2) fewer terminals contained large dense-core vesicles. These findings are consistent with the concept that in the nucleus accumbens, the excitability of the NPY-IR neurons may be more directly modulated by NPY or another transmitter co-existing in the terminals. Catecholamines are known to co-exist with NPY in certain rostrally projecting brainstem nuclei. Therefore, in the two striatal regions, we additionally sought to determine (1) whether the NPY-IR neurons might be modulated by catecholaminergic afferents and (2) whether NPY might co-exist with catecholamines in terminals. Goat antiserum against NPY and rabbit antiserum against tyrosine hydroxylase (TH), the catecholamine-synthesizing enzyme, were simultaneously localized in single sections by PAP and immunoautoradiographic methods, respectively. Quantitative analysis in dually labeled sections from both striatal areas revealed few, if any, direct synaptic contacts between TH-labeled terminals and dendrites containing NPY-like IR. However, there was convergence of separate NPY- and TH-IR terminals on unlabeled dendrites. A few terminals in the nucleus accumbens, but not in the dorsal striatum, showed immunoreactivity methods, to TH and also contained dense-core vesicles with NPY-like IR.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Existence of mutual synaptic relations between corticotropin-releasing factor-containing and somatostatin-containing neurons in the rat hypothalamus.

Light microscopic studies of vibratome sections, which were double-immunostained for corticotropin-releasing factor (CRF) and for somatostatin (SS), suggested the presence of reciprocal synaptic relations between neurons containing immunoreactive (ir) CRF and those containing ir SS in the parvocellular paraventricular nucleus (parvo-PVN) and in the anterior periventricular area (APV) of the rat hypothalamus. In the sections the peptides included in neuronal fibers were labeled black with silver-gold particles, and the peptides included in neuronal cell bodies were labeled brown with diaminobenzidine (DAB). Thereby the brown cell bodies appeared to be surrounded by several black nerve terminals. In electron microscopic studies, the labeling was mostly performed in reverse fashion, because of the convenience for observing the ultrastructural details of the nerve terminals. The neuroplasm of the postsynaptic perikarya and dendrites was labeled with gold-coated silver grains, while the presynaptic axonal terminals were shown with scattered DAB particles. Granular structures in the perikarya or axonal terminals were labeled distinctively. The synaptic morphology appeared to be either symmetric or asymmetric connections. Then we found synaptic connections between presynaptic ir SS containing fiber terminals and postsynaptic ir CRF containing perikarya in the parvo-PVN, and those ir CRF containing fiber terminals and ir SS containing perikarya in the APV. The existence of such a reciprocal association between CRF and SS neurons may suggest that these neuronal systems intervene among different functional systems in the hypothalamus.

Animals↗

Comparison between chlorosomes containing bacteriochlorophyll-c and chlorosomes containing bacteriochlorophyll-d isolated from two substrains of green sulfur photosynthetic bacterium Chlorobium vibrioforme NCIB 8327.

Chlorosomes containing bacteriochlorophyll(BChl)-c and those containing BChl-d were isolated from two substrains of Chlorobium vibrioforme f. sp. thiosulfatophilum NCIB 8327, respectively. The two types of chlorosomes were investigated from the following aspect, what kinds of effects the molecular structure of chlorosomal BChls had on structural and spectroscopic properties of in vivo self-aggregates in chlorosomes without alteration of the other components such as chlorosomal proteins and lipids; both chlorosomes were expected to have the same components except for light-harvesting BChls. In their visible absorption spectra, the differences of Soret and Q(y) peak positions between BChl-c containing and BChl-d containing chlorosomes were similar to the differences between monomeric BChl-c and d. An inverse S-shaped CD signal in the Q(y) region of BChl-d containing chlorosomes was 1.4 times larger than that of BChl-c containing chlorosomes, when the Q(y) absorbance of the two chlorosomes was almost the same. This implies that the excitonic interaction of BChl-d is larger than that of BChl-c in natural chlorosomes. Resonance Raman spectroscopy showed that BChl self-assemblies in both chlorosomes were essentially formed by the same local structural interaction among 3(1)-hydroxy group, 13-keto group, and central magnesium. BChl-d self-aggregates in chlorosomes were more tolerant of 1-hexanol than in vivo BChl-c aggregates, suggesting that the molecular structure of BChl-d provided more stable self-assemblies than BChl-c in natural chlorosomes.

Bacterial Proteins↗

Recognition of hairpin-containing single-stranded DNA by oligonucleotides containing internal acridine derivatives.

Oligodeoxynucleotides with an internal intercalating agent have been targeted to single-stranded sequences containing hairpin structures. The oligonucleotide binds to nonadjacent single-stranded sequences on both sides of the hairpin structure in such a way as to form a three-way junction. The acridine derivative is inserted at a position that allows it to interact with the three-way junction. The melting temperature (Tm) of complexes formed between the hairpin-containing target and oligonucleotides containing one internal acridine derivative was higher than that obtained with the same target and an unmodified oligonucleotide (DeltaTm = +13 degrees C). The internal acridine provided the oligonucleotide with a higher affinity than covalent attachment to the 5' end. Oligonucleotides could also be designed to recognize a hairpin-containing single-stranded nucleic acid by formation of Watson-Crick hydrogen bonds with a single-stranded part and Hoogsteen hydrogen bonds with the stem of the hairpin. An internal acridine derivative was introduced at the junction between the two domains, the double helix domain with Watson-Crick base pairs and the triple helix domain involving Hoogsteen base triplets in the major groove of the hairpin stem. Oligonucleotides with an internal acridine or an acridine at their 5' end have similar binding affinities for the stem-loop-containing target. The bis-modified oligonucleotide containing two acridines, one at the 5' end and one at an internal site, did not exhibit a higher affinity than the oligonucleotides with only one intercalating agent. The design of oligonucleotides with an internal intercalating agent might be of interest to control gene expression through recognition of secondary structures in single-stranded targets.

Acridines↗

Separation and comparison of 2-thioribothymidine-containing transfer ribonucleic acid and the ribothymidine-containing counterpart from cells of Thermus thermophilus HB 8.

For the extreme thermophile Thermus thermophilus HB 8, a positive correlation was observed among the growth temperatures of the cells, the melting temperature, and the 2-thioribothymidine (s2T) content of tRNA extracted from cells grown at various temperatures [Watanabe, K., Shinma, M., Oshima, T., & Nishimura, S. (1976) Biochem. Biophys. Res. Commun. 72, 1137-1144]. On the basis of these observations, studies were carried out from which the following results were obtained. (1) Both RNase T1 and U2 digestions of tRNA gave only four fragments containing s2T or T: s2T psi CGp, s2T psi CAp, T psi CGp, and T psi CAp. For the different growth temperatures, the ratio of the content of s2T psi CGp plus s2T psi CAp to that of T psi CGp plus T psi CAp was almost the same as that of the s2Tp to Tp content reported previously. (2) The midpoint of the s2T-specific circular dichroism spectral change induced by heat was constant for all tRNAs extracted from cells grown at various temperatures, suggesting that the s2T-containing tRNAs melt at about the same temperature, which is independent of the growth temperature of cells. (3) s2T-containing tRNA was separated from the T-containing counterpart quantitatively by a specific modification of s2T with bromoaceto-2,4-dinitroanilide followed by BD-cellulose column chromatography. The molar ratio of the s2T- and T-containing tRNAs was also similar to that of s2Tp to Tp as mentioned above. These results demonstrate that T. thermophilus cells have both s2T- and T-containing tRNAs, whose relative content is controlled by the growth temperature. This phenomenon may be necessary to enable the thermophile to adapt to higher temperatures.

RNA, Transfer↗

Absorption and tissue distribution of zinc, iron and copper by rats fed diets containing lactalbumin, soy and supplemental sulfur-containing amino acids.

Zinc, copper and iron utilization was examined in rats fed diets containing 30% lactalbumin (L); 30% soy assay protein (S) or 30% soy assay protein supplemented with 0.26% cysteine (SC), 0.45% methionine (SM), 0.26% cysteine and 0.45% methionine (SCM) or 0.71% cysteine (SXC). Diets L, SC and SCM contained equal amounts of cysteine; diets L, SM and SCM contained equal amounts of methionine; diets L, SCM, SXC contained equal amounts of sulfur-containing amino acids. Rats fed diet L had significantly higher levels of zinc in tibias, kidneys and plasma; higher levels of copper in kidneys; and higher levels of iron in tibias than rats fed diet S. Rats fed diet L also absorbed (apparent and true) significantly more zinc; excreted significantly more zinc of endogenous origin in the feces; and absorbed (apparent) significantly less copper than rats fed diet S. Rats fed the soy diets supplemented with sulfur-containing amino acids, especially diet SXC, tended to have elevated levels of zinc in their tibias and kidneys and greater apparent and true absorptions of zinc than rats fed diet S. Rats fed diet SXC still had significantly lower zinc levels in tissue than rats fed diet L. Apparent absorption of zinc was similar among rats fed diets L, SCM and SXC.

Amino Acids, Sulfur↗

Fat containing stearic acid increases fecal neutral steroid excretion and catabolism of low density lipoproteins without affecting plasma cholesterol concentration in hamsters fed a cholesterol-containing diet.

To examine the effect of different saturated fatty acids on the dietary cholesterol-induced elevation of serum cholesterol concentration and suppression of LDL catabolism, for 4 wk hamsters were fed purified diets containing 8% purified fats in which saturated fatty acids, lauric, myristic, palmitic and stearic acids were the sole variable. The dietary fat was composed of 50% saturated fatty acid, 30% oleic acid and 20% linoleic acid (polyunsaturated:saturated = 0.4). In hamsters fed the cholesterol-containing diet, fat containing stearic acid, compared with the fats containing other saturated fatty acids resulted in greater fractional catabolic rate of [125I]-labeled homologous LDL, greater fecal excretion of neutral steroids and lower liver cholesterol concentration, although the elevation of serum cholesterol concentration due to consuming a cholesterol-containing diet was not ameliorated. Stearic acid fat resulted in greater excretion of fecal fatty acids and lower apparent absorption of the dietary fats in hamsters fed diets with and without cholesterol. In hamsters fed the cholesterol-free diets, type of dietary fat did not affect the fractional catabolic rate of LDL, although stearic acid fat resulted in greater fecal neutral steroid excretion and lower serum and liver cholesterol concentrations. These observations suggested that purified fat containing stearic acid results in lower plasma cholesterol concentration in hamsters via stimulation of neutral steroid excretion, but addition of cholesterol to the diets obscures this effect.

Adipose Tissue↗

Deposits on single use containers--a social cost-benefit analysis of the Danish deposit system for single use drink containers.

This study compares the social costs and environmental benefits of collecting single use drink containers through the Danish deposit system with the social costs and benefits of treating the containers as part of the municipal waste-disposal system. It focuses on single use polyethylene terphthalate and glass bottles, and steel and aluminium cans. The social costs of handling these containers in the deposit system includes the costs of collection, sorting, and transportation, adjusted against the profit from selling the collected material for recycling. The social cost of incinerating these containers as municipal waste consists of the expenses for the collection, incineration of the containers and disposal of ashes. If there is any income from energy generation accompanying incineration, this is adjusted against costs. The main environmental effects related to both strategies are quantified, valuated and included in the assessment. The results of the analysis show that there are significant social costs compared to the benefits connected with the new deposit system. This is true for all four types of single use drink containers examined. All in all, Denmark bears a net social cost of 6.7 to 8.1 million Euros per year compared to a baseline of incineration with energy recovery.

Aluminum↗

[Determination of the desirable epinephrine concentration containing in dental local anesthetics. Comparison between two lidocaine solutions containing 1/80,000 and 1/200,000 epinephrine].

This study is a pilot study to determine the desirable epinephrine concentration containing in dental local anesthetics. Two percent lidocaine solution containing 1/80,000 and 1/200,000 epinephrine were compared in view points of onset and duration of anesthesia and hemodynamic responses after conduction and infiltration anesthesia in oral cavities of six voluntary dental students. Conduction anesthesia to the right inferior alveolar nerve, using 2% lidocaine solution containing 1/80,000 and 1/200,000 epinephrine showed no significant difference in onset and duration of anesthesia, changes in blood pressure and pulse rate. Duration of anesthesia determined by pin prick showed the longest in infiltration anesthesia, using 2% lidocaine solution containing 1/80,000 epinephrine, (103.4 +/- 18.5 min.), and followed by that containing 1/200,000 epinephrine (52.0 +/- 13.0 min.) and that excluding epinephrine (23.0 +/- 5.1 min.). These findings suggested that the desirable epinephrine concentration containing in dental local anesthetics may be 1/200,000, judging from the time of a dental practice.

Anesthesia, Dental↗

Characterization of lipoprotein particles isolated by immunoaffinity chromatography. Particles containing A-I and A-II and particles containing A-I but no A-II.

Two populations of A-I-containing lipoprotein particles: A-I-containing lipoprotein with A-II (Lp (A-I with A-II], and A-I-containing lipoprotein without A-II (Lp (A-I without A-II] have been isolated from plasma of 10 normolipidemic subjects by immunoaffinity chromatography and characterized. Both types of particles possess alpha-electrophoretic mobility and hydrated density in the range of plasma high-density lipoproteins (HDL). Lp (A-I without A-II) and Lp (A-I with A-II) are heterogeneous in size. Lp (A-I without A-II) comprised two distinct particle sizes with mean apparent molecular weight and Stokes diameter of 3.01 X 10(5), and 10.8 nm for Lp (A-I without A-II)1, and 1.64 X 10(5), and 8.5 nm for Lp (A-I without A-II)2. Lp (A-I with A-II) usually contained particles of at least three distinct molecular sizes with mean apparent molecular weight and Stokes diameter of 2.28 X 10(5) and 9.6 nm for Lp (A-I with A-II)1, 1.80 X 10(5) and 8.9 nm for Lp (A-I with A-II)2, and 1.25 X 10(5) and 8.0 nm for Lp (A-I with A-II)3. Apoproteins C, D, and E, and lecithin:cholesterol acyltransferase (LCAT) were detected in both Lp (A-I without A-II) and Lp (A-I with A-II) with most of the apoprotein D, and E, and LCAT (EC 2.3.1.43) in Lp (A-I with A-II) particles. Lp (A-I without A-II) had a slightly higher lipid/protein ratio than Lp (A-I with A-II). Lp (A-I with A-II) had an A-I/A-II molar ratio of approximately 2:1. The percentage of plasma A-I associated with Lp (A-I without A-II) was highly correlated with the A-I/A-II ratio of plasma (r = 0.96, n = 10). The variation in A-I/A-II ratio of HDL density subfractions therefore reflects different proportions of two discrete types of particles: particles containing A-I and A-II in a nearly constant ratio and particles containing A-II but no A-II. Each type of particle is heterogeneous in size and in apoprotein composition.

Animals↗

Morphometric evaluation of immunoglobulin A-containing and immunoglobulin G-containing cells and T cells in duodenal mucosa from healthy dogs and from dogs with inflammatory bowel disease or nonspecific gastroenteritis.

OBJECTIVE: To investigate the distribution of IgA- and IgG-containing cells and T cells in the villi of duodenal mucosa from healthy dogs and from dogs with inflammatory bowel disease (IBD) of gastroenteritis. DESIGN: Case-control study. ANIMALS: 28 dogs, grouped according to clinical and histologic criteria: 11 dogs with IBD, 8 dogs with non-specific gastroenteritis, and 9 healthy dogs. PROCEDURE: Endoscopic biopsy specimens of duodenal mucosa from each dog were stained specifically for IgA and IgG heavy chains and pan T-cell (CD3) antigen, using immunoperoxidase techniques. Morphometric analysis, performed via an image-analysis system, was used to count IgA- and IgG-containing cells and T cells within paired contiguous villi from each dog. RESULTS: cells were the predominant immune cell type in all groups of dogs. Significant differences in the villus distribution of IgA- and IgG-containing cells and T cells were not observed. Healthy dogs had significantly higher T-cell counts than had dogs with IBD or gastroenteritis. Dogs with nonspecific gastroenteritis had a significantly higher concentration of IgA-containing cells than the other groups of dogs had. Significant group differences for IgG-containing cells also were evident, with dogs with IBD having the lowest cell counts. CONCLUSIONS AND CLINICAL RELEVANCE: High concentrations of IgA- and IgG-containing cells and T cells in the villus lamina propria cannot be reliably used to distinguish IBD from other intestinal disorders in dogs. Evaluation of T cells may be the most discriminatory method for differentiating dogs with IBD from clinically normal dogs via examination of intestinal biopsy specimens.

Animals↗