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21.
Phorbol ester and dibutyryl cyclic AMP reduce content and efflux of taurine in primary cerebellar astrocytes in culture 总被引:1,自引:0,他引:1
In 16-18 days in vitro (DIV) primary astrocyte cultures prepared from 7- to 9-day-old rats, 48 h exposure to 12,13-phorbol dibutyrate (PDBU) (1 microM) or dibutyryl cAMP (dbcAMP) (1 mM) reduced cellular taurine content, and both basal and 50 mM K+-evoked taurine efflux, but did not alter cellular glutamate or total protein content. Decreases in cellular taurine content first became apparent between 1 and 6 h and were maximal after 24 h. Treatment also rapidly altered astrocyte morphology to a more process-bearing form within 1 h. In contrast, fibroblast growth factor (FGF), epidermal growth factor (EGF), dbcGMP and alpha-PDBU did not affect cellular morphology, amino acid content or taurine efflux at any time tested. These findings suggest that, while protein kinase C translocation and adenylate cyclase activation may be only indirectly involved in the regulation of astrocyte morphology, long-term decreases in cellular taurine content and efflux may be the more direct result of these second messenger systems. 相似文献
22.
Jain JK Dutton C Harwood B Meckstroth KR Mishell DR 《Human reproduction (Oxford, England)》2002,17(6):1477-1482
BACKGROUND: Vaginal misoprostol has been shown to be an effective single agent for medical abortion. This randomized, double-blinded, placebo-controlled trial compared a regimen of mifepristone and misoprostol with misoprostol alone for termination of early pregnancy. METHODS: 250 women with gestations < or = 56 days were randomized by a random number table to receive either 200 mg mifepristone orally or placebo followed 48 h later by 800 microg vaginal misoprostol. Administration of misoprostol was repeated every 24 h up to three doses if abortion failed to occur. Abortion success was defined as complete abortion without the use of surgical aspiration. RESULTS: Successful medical abortions occurred in 114 out of 119 subjects (95.7%) after mifepristone followed by vaginal misoprostol. In all, 110 out of 125 subjects (88.0%) successfully aborted after placebo and vaginal misoprostol. The higher success rate of complete abortion with the mifepristone and misoprostol regimen was statistically significant compared with the placebo and misoprostol regimen (P < 0.05). CONCLUSIONS: A regimen of mifepristone and misoprostol was significantly more effective for termination of pregnancies < or = 56 days than misoprostol alone. The 88% efficacy obtained with vaginal misoprostol alone may be clinically acceptable when mifepristone is not available. 相似文献
23.
The significance of the protein carrier in the stimulation of DNA synthesis by hapten—protein conjugates in the secondary response
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Rabbits were immunized with 2,4-dinitrophenyl (DNP)—protein conjugates. Spleen cell suspensions were prepared and incubated in the presence of various DNP—protein conjugates, the proteins alone, and DNP—lysine. The antigen dependent stimulation of DNA synthesis was used as a measure of the antigenic `activity' of the DNP preparations. It was found that the cells were strongly stimulated by the DNP—protein conjugates used for immunization, and weakly stimulated by the protein alone. Highly substituted DNP—protein conjugates were markedly more effective than lightly substituted conjugates. DNP-conjugates with proteins other than the one used during immunization were inactive. DNP—lysine alone was inactive but inhibited stimulation by the DNP—protein conjugate used for immunization. The significance of these findings is discussed. 相似文献
24.
Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion 总被引:9,自引:2,他引:9
Submicroscopic deletions of the Y chromosome and polymorphisms of the
androgen receptor (AR) gene in the X chromosome have been observed in men
with defective spermatogenesis. To further define the subregions/genes in
the Y chromosome causing male infertility and its relationship to
polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of
202 subfertile males and 101 healthy fertile controls of predominantly
Chinese ethnic origin. Y microdeletions were examined with 16
sequence-tagged site (STS) probes, including the RBM and DAZ genes,
spanning the AZFb and AZFc subregions of Yq11, and related to the size of
trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions
were detected and confirmed in three out of 44 (6.8%) of azoospermic and
three out of 86 (3.5%) severely oligozoospermic patients. No deletions were
detected in any of the patients with sperm counts of >0.5 x 10(6)/ml,
nor in any of the 101 fertile controls. All six affected patients had
almost contiguous Y microdeletions spanning the entire AZFc region
including the DAZ gene. The AZFb region, containing the RBM1 gene, was
intact in five of the six subjects. Y deletions were not found in those
with long AR polyglutamine tracts. Our study, the first in a Chinese
population, suggest a cause and effect relationship between Y
microdeletions in the AZFc region (possibly DAZ), and azoospermia or
near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear
to be independent contributors to male infertility.
相似文献
25.
The presence of autoreactive lymphocytes was investigated in murine lymphohaematopoietic chimeras. In this report we demonstrate the presence of precursors of host-reactive cytotoxic effector T lymphocytes in parent leads to F1 chimeras. Lymphocytes from these chimeras display cytotoxic activity towards the non-shared major histocompatibility complex (MHC) antigens of the host following activation with the polyclonal T-cell activator concanavalin A. These host-reactive cells were found despite the apparent absence of lymphocytes demonstrating autoreactivity in other experimental systems: mixed lymphocyte reaction, cell-mediated lympholysis, positive allogeneic effect and negative allogeneic effect. Animals possessing precursors of these cytotoxic effector cells also possess precursors of cytotoxic effector cells capable of generating an MHC-restricted anti-minor histocompatibility antigen response. The results are discussed in reference to the role of the thymus in effecting self non-self discrimination. 相似文献
26.
Catt SL; Sakkas D; Bizzaro D; Bianchi PG; Maxwell WM; Evans G 《Molecular human reproduction》1997,3(9):821-825
Controlling the sex of offspring by the separation of X and Y
chromosome-bearing spermatozoa using flow cytometry has been reported as a
clinical technique aiding prevention of X-linked diseases. Although this
technique has resulted in several hundred normal births in animals and at
least one human birth, there is still concern over its genetic safety due
to the involvement of two potentially mutagenic agents: UV light and the
fluorochrome dye, Hoechst 33342 (H33342). Human spermatozoa, particularly
those considered abnormal, may be more likely to suffer DNA damage
following exposure to mutagenic agents, compared with other mammalian
species. The stability of normal fresh and decondensed human spermatozoa
were examined after exposure to a range of levels of UV and H33342
staining, using an assay that detects endogenous nicks in the DNA of
spermatozoa. The stability of abnormal and normal, fresh and frozen-thawed
human spermatozoa was examined following UV laser, H33342 staining and flow
cytometry treatments utilizing the same assay. There was an increase in the
presence of endogenous nicks when spermatozoa were decondensed compared
with fresh spermatozoa. There was no increase in the incidence of nicks in
any group of spermatozoa after UV and fluorochrome exposure compared with
controls without exposure.
相似文献
27.
Winberg JO; Hammami-Hauasli N; Nilssen O; Anton-Lamprecht I; Naylor SL; Kerbacher K; Zimmermann M; Krajci P; Gedde-Dahl T Jr; Bruckner-Tuderman L 《Human molecular genetics》1997,6(7):1125-1135
Dystrophic epidermolysis bullosa (EBD) is a clinically heterogeneous skin
disorder, characterized by abnormal anchoring fibrils (AF) and loss of
dermal-epidermal adherence. EBD has been linked to the COL7A1 gene at
chromosome 3p21 which encodes collagen VII, the major component of the AF.
Here we investigated two unrelated EBD families with different clinical
phenotypes and novel combinations of recessive and dominant COL7A1
mutations. Both families shared the same recessive heterozygous 14 bp
deletion at the exon-intron 115 boundary of the COL7A1 gene. The deletion
caused in-frame skipping of exon 115 and the elimination of 29 amino acid
residues from the pro-alpha1(VII) polypeptide chain. As a result,
procollagen VII was not converted to collagen VII and the C-terminal NC-2
propeptide which is normally removed from the procollagen VII prior to
formation of the anchoring fibrils was retained in the skin. All affected
individuals also carried missense mutations in exon 73 of COL7A1 which lead
to different glycine- to-arginine substitutions in the triple-helical
domain of collagen VII. Combination of the deletion mutation with a G2009R
substitution resulted in a mild phenotype. In contrast, combination of the
deletion with a G2043R substitution led to a severe phenotype. The G2043R
substitution was a de novo mutation which alone caused a mild phenotype.
Thus, different combinations of dominant and recessive COL7A1 mutations can
modulate disease activity of EBD and alter the clinical presentation of the
patients.
相似文献
28.
Type 1 and type 2 tumor infiltrating effector cell subpopulations in progressive breast cancer 总被引:4,自引:0,他引:4
Effector T cells fall into two subpopulations based on cytokine-secretion. Type 1 cells secrete IFN-gamma, whereas type 2 cells secrete IL-4, IL-10, and GM-CSF. NKT cells represent a third subpopulation that secretes similar cytokines and have been associated with immunoregulation. Using the TS/A adenocarcinoma, we assessed the phenotype and kinetics of tumor-infiltrating lymphocytes (TIL) in mice challenged subcutaneously in the mammary region. Flow cytometric analysis shows that T cells do not infiltrate the primary tumor site until days 7-14 following tumor challenge. Both CD4 and CD8 TILs were predominantly CD44(High) and expressed CD25, CD69, and CD95 cell surface activation markers. Activated CD4/CD44(High) TIL numbers reached peak levels at day 21 that precipitously decreased by day 28 whereas corresponding CD8 cell numbers progressively increased, however, at lower levels and with later kinetics. Intracellular cytokine staining showed that greater numbers of IL-4-producing Th2 cells were elicited and with earlier kinetics than that of IFN-gamma-producing Th1 cells. T cells co-expressing DX5 (CD3(+)/DX5(+)) emerged (>21 days), suggesting a recruitment of NK-like T cells at later stages of tumor progression. Moreover, tumors selectively up-regulated TGF-beta, MIF, and IP-10 gene expression at times as early as day 4, with peak levels at day 7 in vivo. Such gene expression remained elevated and correlated with a continued progression in tumor growth suggesting that preferential effector cell recruitment and production of select factors during different stages of tumor maturation may aid in regulating effective endogenous antitumor responses in progressive breast cancer. 相似文献
29.
Iolo Madoc-Jones PhD MSc BA Hons CQSW Sarah Wadd PhD MSc BSc Lawrie Elliott PhD MA PG Cert Anne Whittaker PhD BSc Post Grad Dip RNMH RMN Laura Adnum PhD MSc BSc Ciara Close PhD MSc BSc Jennifer Seddon PhD MSc BSc Maureen Dutton Michelle McCann MA CQSW Fiona Wilson BA 《Health & social care in the community》2021,29(2):344-352
Cognitive Impairment (CI) screening is recommended for those engaged in harmful levels of alcohol use. However, there is a lack of evidence on implementation. This paper explores the barriers and facilitators to CI screening experienced across a service specifically for older drinkers. The findings draw on data gathered as part of an evaluation of a multilevel programme to reduce alcohol-related harm in adults aged 50 and over in five demonstration areas across the United Kingdom. It is based on qualitative interviews and focus groups with 14 service providers and 22 service users. Findings are presented thematically under the section headings: acceptability of screening, interpretation and making sense of screening and treatment options. It is suggested that engagement with CI screening is most likely when its fit with agency culture and its purpose is clear; where service providers have the technical skills to administer and discuss the results of screening with service users; and where those undertaking screening have had the opportunity to reflect on their own experience of being screened. Engagement with CI screening is also most likely where specific intervention pathways and engagement practices can be accessed to respond to assessed need. 相似文献
30.
Ballantyne J Hollman AS Hamilton R Bradnam MS Carachi R Young DG Dutton GN 《Clinical radiology》1999,54(11):740-742
AIM: Early diagnosis of acute intracranial hypertension is essential to enable prompt, optimal treatment. The optic nerve sheath diameter (ONSD) is increased in raised ICP and there has been recent interest in the use of ultrasound to diagnose and indirectly monitor raised ICP by ONSD measurement. The advantages of the technique include its non-invasiveness, wide availability, portability, low cost and the absence of ionizing radiation. This prospective study was designed to establish the range of normal values for ONSD in infants and children up to 15 years of age. PATIENTS AND METHODS: One hundred and two children attending the hospital for other reasons were recruited to the study. Three measurements of the ONSD were taken for each eye, 3 mm behind the optic nerve head using a 7 MHz sector probe. RESULTS: The range for ONSD was 2.1-4.3 mm, mean 3.08 (SD 0.36). There were no significant differences on ONSD measurement between boys and girls (P = 0.59) or between right and left eyes (P=0.66). When the data were grouped and analysed, a correlation between increasing age and increasing ONSD was seen (r2=0.48), with the greatest increase occurring in the first 2 months of life. CONCLUSION: Using the technique described here, our results suggest that an ONSD of greater than 4 mm in infants less than 1 year, and 45 mm or greater in older children, should be regarded as abnormal. 相似文献