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21.
Staphylococcal exopolysaccharides inhibit lymphocyte proliferative responses by activation of monocyte prostaglandin production.
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The glycocalyx (exopolysaccharides) of Staphylococcus epidermidis has been reported to inhibit a variety of host defense mechanisms. We have examined the inhibitory effects of glycocalyx on the proliferation of human peripheral blood mononuclear cells (PBMC) and the mechanism of this inhibition. Glycocalyx isolated and partially purified under endotoxin-free conditions from defined liquid medium cultures of S. epidermidis and Staphylococcus lugdunensis inhibited the proliferative response of PBMC when added to cultures at 10 to 100 micrograms/ml. Glycocalyx-mediated inhibition of phytohemagglutinin-stimulated proliferation of PBMC required the presence of plastic-adherent peripheral blood monocytes. Culture supernatants of monocytes stimulated with glycocalyx contained a soluble factor that inhibited the proliferation of monocyte-depleted PBMC. This soluble inhibitory factor was not produced in the absence of glycocalyx or in the presence of both glycocalyx and indomethacin. Analysis of the supernatants of cultures of adherent monocytes revealed that glycocalyx from S. epidermidis and from S. lugdunensis could activate monocyte production of prostaglandin E2 (PGE2), human interleukin-1, and tumor necrosis factor alpha. The addition of purified PGE2, at the same levels of PGE2 (greater than or equal to 10(-9) M) generated in the monocyte cultures, to PBMC cultures resulted in a similar inhibition of proliferative responses. It is concluded that, contrary to previous suggestions, the bacterial glycocalyx does not have a direct inhibitory effect on T lymphocytes. However, it does appear that glycocalyx from coagulase-negative staphylococci can activate monocyte PGE2 production and that it is this activity that in turn contributes to the inhibition of T-cell proliferation. 相似文献
22.
Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA 总被引:2,自引:2,他引:2
Rozmahel R; Gyomorey K; Plyte S; Nguyen V; Wilschanski M; Durie P; Bear CE; Tsui LC 《Human molecular genetics》1997,6(7):1153-1162
We have used a mouse model to study the ability of human CFTR to correct
the defect in mice deficient of the endogenous protein. In this model,
expression of the endogenous Cftr gene was disrupted and replaced with a
human CFTR cDNA by a gene targeted 'knock-in' event. Animals homozygous for
the gene replacement failed to show neither improved intestinal pathology
nor survival when compared to mice completely lacking CFTR. RNA analyses
showed that the human CFTR sequence was transcribed from the targeted
allele in the respiratory and intestinal epithelial cells. Furthermore, in
vivo potential difference measurements showed that basal CFTR chloride
channel activity was present in the apical membranes of both nasal and
rectal epithelial cells in all homozygous knock-in animals examined. Ussing
chamber studies showed, however, that the cAMP-mediated chloride channel
function was impaired in the intestinal tract among the majority of
homozygous knock-in animals. Hence, failure to correct the intestinal
pathology associated with loss of endogenous CFTR was related to
inefficient functional expression of the human protein in mice. These
results emphasize the need to understand the tissue- specific expression
and regulation of CFTR function when animal models are used in gene therapy
studies.
相似文献
23.
Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases 总被引:5,自引:5,他引:5
The expansion of trinucleotide repeat sequences is associated with several
neurodegenerative diseases. The mechanism of this expansion is unknown but
may involve slipped-strand structures where adjacent rather than perfect
complementary sequences of a trinucleotide repeat become paired. Here, we
have studied the interaction of the human mismatch repair protein MSH2 with
slipped-strand structures formed from a triplet repeat sequence in order to
address the possible role of MSH2 in trinucleotide expansion. Genomic
clones of the myotonic dystrophy locus containing disease-relevant lengths
of (CTG)n x (CAG)n triplet repeats were examined. We have constructed two
types of slipped-strand structures by annealing complementary strands of
DNA containing: (i) equal numbers of trinucleotide repeats (homoduplex
slipped structures or S-DNA) or (ii) different numbers of repeats
(heteroduplex slipped intermediates or SI-DNA). SI-DNAs having an excess of
either CTG or CAG repeats were structurally distinct and could be separated
electrophoretically and studied individually. Using a band-shift assay, the
MSH2 was shown to bind to both S-DNA and SI-DNA in a structure- specific
manner. The affinity of MSH2 increased with the length of the repeat
sequence. Furthermore, MSH2 bound preferentially to looped-out CAG repeat
sequences, implicating a strand asymmetry in MSH2 recognition. Our results
are consistent with the idea that MSH2 may participate in trinucleotide
repeat expansion via its role in repair and/or recombination.
相似文献
24.
Jeffrey P. Gardner Marguerite A. Stout S. Richard Harris 《Pflügers Archiv : European journal of physiology》1989,414(4):484-491
The calmodulin (CaM) content of intact and chemically skinned strips of rat caudal artery was measured using a125I-CaM radioimmunoassay. The total CaM measured following homogenization of arterial tissue with EGTA and EGTA/Triton X-100 was 2.58 mol/kg wet tissue. Based on a smooth muscle volume of 40%, this value corresponds to a cellular CaM concentration of 6.5 M. Approximately 97% of total CaM was soluble and approximately 3% was EGTA-nonextractable. Permeabilization of the plasmalemma with 0.15 mg/ml saponin or 0.5% Triton X-100 caused significant detergent-dependent loss of CaM. At the end of a 1 h skinning period, tissues exposed to saponin lost 30% of total CaM. By comparison, tissues skinned under the same conditions with Triton X-100 lost 50%. During a subsequent 4h exposure to relaxing solution, total tissue CaM continued to decline. The exponential loss over the 5h period was described by a first order model having diffusible and nondiffusible CaM components. The diffusible CaM component of saponin skinned tissue (59%) was significantly less than the diffusible component of those skinned with Triton X-100 (88%); however, the rate coefficients for CaM diffusion (0.78 h–1 and 0.91 h–1, respectively) did not statistically differ. The nondiffusible component of CaM was significantly larger in saponin treated strips (42%) than in Triton X-100 permeabilized tissue (12%). Arterial strips skinned with Triton X-100, which were subsequently exposed to relaxing solution for up to 22 h, lost significantly more CaM than those retained in Triton X-100 skinning solution for a comparable duration These studies demonstrate the diffusion of CaM from detergent skinned arterial strips and characterize the time course of that loss. 相似文献
25.
Inhibition of excitatory neurotransmission with kynurenate reduces brain edema in neonatal anoxia 总被引:1,自引:0,他引:1
Excitatory amino acid neurotransmitters have been implicated in fostering brain edema and neuronal death in ischemia. As both of these processes are involved in nervous system damage during neonatal anoxia, the effect of blockade of cell excitation with kynurenate upon brain water was studied following anoxic-ischemic brain injury in neonatal rats. Such treatment attenuated brain edema immediately after, and 24 h following anoxia-ischemia. 相似文献
26.
L C Stout 《Human pathology》1985,16(10):1075-1076
The case of a patient with primary hyperparathyroidism in whom water-clear-cell hyperplasia (WCCH) involved only the superior glands, and disproportionately so, is presented. In addition, unlike the cases of WCCH described previously, a rim of normal parathyroid tissue was observed at the periphery of each gland in this case. It is speculated that these findings are not necessarily peculiar, but may reflect an earlier stage of the disease. Such cases may mimic parathyroid adenoma, thereby leading to inadequate surgical therapy. 相似文献
27.
28.
Russell EJ; Geremia GK; Johnson CE; Huckman MS; Ramsey RG; Washburn-Bleck J; Turner DA; Norusis M 《Radiology》1987,165(3):609-617
Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes. 相似文献
29.
Rao VM; Dalinka MK; Mitchell DG; Spritzer CE; Kaplan F; August CS; Axel L; Kressel HY 《Radiology》1986,161(1):217-220
Four patients with proved osteopetrosis (three with the infantile malignant form and one with the benign form) were examined with magnetic resonance imaging at 1.5 T. All patients were studied in the coronal and sagittal planes using both short and long repetition time/echo time sequences. The infantile malignant form was characterized by a complete lack of signal from the marrow alternating with a signal intensity equivalent to that of the intervertebral disks, resulting in a "stepladder" appearance. In the benign form or after successful marrow transplantation in the infantile malignant form, intermediate or high signal intensity in the vertebrae was noted, suggesting the presence of some marrow elements. 相似文献
30.
Biological thiols are known to play an important role in thedetoxification of xenobiotics, including chemical carcinogens.To determine the influence of cellular thiols on carcinogeninduction of hepatic DNA damage in the rat, diethylmaleate (DEM)administration was used to deplete intracellular gluta-thione(GSH). The effects of administration of the synthetic thiols,N-acetylcysteine (NAC) and alpha-mercaptopropionyl-glycine (MPG),on the induction of DNA lesions were also examined. Pretreatmentwith DEM reduced liver GSH levels by >70%. As assessed bythe technique of alkaline elution, subsequent administrationof N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) resulted inDNA damage 4 h post MNNG treatment which was 4- to 8-fold greaterthan that induced in the livers of rats treated with MNNG alone.However, DEM pretreatment had little effect on the extent ofDNA damage induced by methylnitrosourea (MNU). DEM alone didnot cause any measurable DNA damage. Pretreatment with MPG orNAC reduced MNNG-induced DNA damage by as much as 77%. In contrast,MNU-induced DNA damage was increased by MPG treatment whereasNAC treatment was without effect. These results indicated thatin the rat liver, the activity of some DNA alkylating agentsmay be modulated in varying degree by the concentration of intracellularthiols. These data support the notion that thiols play an importantrole in protection against carcinogen damage, and that syntheticthiols such as MPG and NAC may be useful as anti-carcinogenicagents against certain carcinogens. 相似文献