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51.
Flupirtine ameliorates ischaemic-like death of rat retinal ganglion cells by preventing calcium influx 总被引:4,自引:0,他引:4
The effect of flupirtine on the loss of retinal ganglion cells following transient elevation of intraocular pressure (experimental ischaemia) or NMDA-induced excitotoxicity was studied. Ischaemia (60 min) or intravitreal injection of NMDA (20 nmol) caused a decrease in Thy-1 mRNA and Thy-1 immunoreactivity which are associated with ganglion cells. Administration of flupirtine counteracted these changes. Moreover, flupirtine dose-dependently inhibited NMDA-induced 45Ca(2+) influx into cultured cortical neurones and retinal pieces in vitro with maximal inhibition being observed at 200 microM. A similar concentration of flupirtine failed to inhibit kainate-stimulated calcium influx into cultured cortical neurones. In addition, flupirtine had no significant effect on [3H]nitrendipine or [3H]diltiazem binding to cortical membranes. The present studies are consistent with previous findings which suggested flupirtine to act as a NMDA antagonist by a mechanism that still remains to be clarified. 相似文献
52.
Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients. 总被引:8,自引:0,他引:8
Jenny C Chang Eric C Wooten Anna Tsimelzon Susan G Hilsenbeck M Carolina Gutierrez Yee-Lu Tham Mamta Kalidas Richard Elledge Syed Mohsin C Kent Osborne Gary C Chamness D Craig Allred Michael T Lewis Helen Wong Peter O'Connell 《Journal of clinical oncology》2005,23(6):1169-1177
PURPOSE: Chemotherapy for operable breast cancer decreases the risk of death. Docetaxel is one of the most active agents in breast cancer, but resistance or incomplete response is frequent. PATIENTS AND METHODS: Core biopsies from 24 patients were obtained before treatment with neoadjuvant docetaxel (four cycles, 100 mg/m(2) every 3 weeks), and response was assessed after chemotherapy. After 3 months of neoadjuvant chemotherapy, surgical specimens (n = 13) were obtained, and laser capture microdissection (LCM; n = 8) was performed to enrich for tumor cells. From each core, surgical, and LCM specimen, sufficient total RNA (3 to 6 microg) was extracted for cDNA array analysis using the Affymetrix HgU95-Av2 GeneChip (Affymetrix, Santa Clara, CA). RESULTS: From the initial core biopsies, differential patterns of expression of 92 genes correlated with docetaxel response (P = .001). However, the molecular patterns of the residual cancers after 3 months of docetaxel treatment were strikingly similar, independent of initial sensitivity or resistance. This relative genetic homogeneity after treatment was observed in both LCM and non-LCM surgical specimens. The residual tumor after treatment in tumors that were initially sensitive indicates selection of a residual and resistant subpopulation of cells. The gene expression pattern was populated by genes involved in cell cycle arrest at G(2)M (eg, mitotic cyclins and cdc2) and survival pathways involving the mammalian target of rapamycin. CONCLUSION: A specific and consistent gene expression pattern was found in residual tumors after docetaxel treatment. These profiles provide therapeutic targets that could lead to improved treatment. 相似文献
53.
A.H. Gerulath A.J. Dembo S. Aitken I.C. Quirt R. Osborne M. Blackstein W.D. Rider 《Gynecologic oncology》1986,25(3):294-301
From 1971 to 1981, twenty patients with poor-prognosis metastatic gestational trophoblastic neoplasia (GTN) were treated with moderate-dose methotrexate (1 g) and folinic-acid rescue (MD-MTX-FAR) as initial therapy. Seven (35%) were cured with MD-MTX-FAR, and salvage chemotherapy was successful in an additional seven, for a total cure rate of 70%. The ultimate outcome is similar to that reported for MAC triple therapy during this era. Hematologic and mucosal toxicity were negligible and no serious complications were encountered. We now use combination chemotherapy in patients with poor-prognosis GTN as first-line treatment. However, these results suggest that there may be advantages to the incorporation of MD-MTX-FAR in combination regimens in place of low-dose methotrexate, because of reduced toxicity and potential benefits for the prophylaxis and treatment of cerebral metastases. 相似文献
54.
Background Hereditary pancreatitis is an important cause of chronic pancreatitis, which may result in endocrine and exocrine failure.
This may necessitate simultaneous pancreas and kidney transplant (SPK). Bladder drainage of the exocrine secretions may cause
problems.
Aim To report one such case and its surgical correction.
Methods A 20-year-old male with insulin-dependent diabetes mellitus secondary to idiopathic chronic pancreatitis had a SPK with bladder
drainage. Urological and metabolic complications secondary to the drainage of pancreatic secretions, rich in proteolytic enzymes
required convertion from bladder to enteric drainage.
Results He was able to discontinue his pancreatic enzyme supplements, ceased to have steatorrhoea and gained weight. He was referred
to the €pean Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (€PAC), hereditary pancreatitis was confirmed
by genetic analysis.
Conclusion Enteric-drained pancreas transplantation is a successful treatment for exocrine as well as endocrine pancreatic failure and
should be considered as a treatment option in patients with chronic pancreatitis. 相似文献
55.
Background Cancer patients undergoing major abdominal or pelvic surgery are at considerable risk of venous thromboembolism (VTE). The
genesis of thromboses in malignancy is complicated, and reflects the interaction and derangement of multiple molecular pathways.
Furthermore, the nature and location of the cancer, as well as the type surgery involved, are thought to affect the level
of VTE risk. These considerations may therefore affect treatment decisions.
Methods We performed multiple Medline searches with terms including but not limited to VTE, cancer, surgery, abdominal, colorectal,
unfractionated heparin (UFH), and low-molecular-weight heparin (LMWH) to identify reviews, meta-analyses, nonrandomized and
randomized controlled trials, and clinical guidelines relating to management of VTE in patients with abdominal cancer.
Results VTE incidence in patients with malignancy varied according to cancer type, location, stage of progression, and the use of
catheters and/or chemotherapy. Thromboprophylaxis with UFH or LMWH reduces the risk of developing VTE in these patients. However,
LMWHs have a favorable risk-benefit profile over UFH and extending the duration prophylaxis may improve outcomes.
Conclusion A number of recommendations can be made for the prevention of VTE in patients undergoing abdominal or pelvic surgery for cancer:
(1) risk-stratify all patients according to defined evidence-based guidelines; (2) for most abdominal surgical oncology patients
at risk, use of both an anticoagulant and mechanical means are indicated and beneficial; and (3) consider extended-duration
prophylaxis (up to 28 days) in those patients with major abdominal/pelvic operations and impaired mobility, preferably with
LMWH. 相似文献
56.
Gang Chen Alexander J Chan Josiah I Chung Jessica C Jang Lisa C Osborne Meera G Nair 《Gut microbes》2014,5(3):363-368
Citrobacter rodentium infection is a murine model of pathogenic Escherichia coli infection that allows investigation of the cellular and molecular mechanisms involved in host-protective immunity and bacterial-induced intestinal inflammation. We recently demonstrated that following C. rodentium infection, the absence of Resistin-Like Molecule (RELM) α resulted in attenuated Th17 cell responses and reduced intestinal inflammation with minimal effects on bacterial clearance. In this addendum, we investigated the cytokine modulatory effects of RELMα and RELMα expression in the intestinal mucosa following C. rodentium infection. We show that in addition to promoting Th17 cytokine responses, RELMα inhibits Th2 cytokine expression and Th2-cytokine effector macrophage responses in the C. rodentium-infected colons. Second, utilizing reporter C. rodentium, we examined RELMα expression and macrophage recruitment at the host pathogen interface. We observed infection-induced macrophage infiltration and RELMα expression by intestinal epithelial cells. The influence of infection-induced RELMα on macrophage recruitment in the intestine is discussed. 相似文献
57.
58.
Osborne AH Vance D Rohling EJ Barton N Rogerson M Fello N 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(43):16444-16447
It is widely accepted that modern humans originated in sub-Saharan Africa approximately 150-200 thousand years ago (ka), but their route of dispersal across the currently hyperarid Sahara remains controversial. Given that the first modern humans north of the Sahara are found in the Levant approximately 120-90 ka, northward dispersal likely occurred during a humid episode in the Sahara within Marine Isotope Stage (MIS) 5e (130-117 ka). The obvious dispersal route, the Nile, may be ruled out by notable differences between archaeological finds in the Nile Valley and the Levant at the critical time. Further west, space-born radar images reveal networks of-now buried-fossil river channels that extend across the desert to the Mediterranean coast, which represent alternative dispersal corridors. These corridors would explain scattered findings at desert oases of Middle Stone Age Aterian lithic industries with bifacial and tanged points that can be linked with industries further to the east and as far north as the Mediterranean coast. Here we present geochemical data that demonstrate that water in these fossil systems derived from the south during wet episodes in general, and penetrated all of the way to the Mediterranean during MIS 5e in particular. This proves the existence of an uninterrupted freshwater corridor across a currently hyperarid region of the Sahara at a key time for early modern human migrations to the north and out of Africa. 相似文献
59.
A M Johnson A Petherick S J Davidson R Brettle M Hooker L Howard K A McLean L E Osborne R Robertson C Sonnex 《AIDS (London, England)》1989,3(6):367-372
Future heterosexual spread of HIV will in part depend on the efficiency of transmission from men to women and from women to men. We studied seventy-eight female sexual partners of men infected with HIV and 18 male sexual partners of infected women. Participants were interviewed concerning sexual practices, use of contraception and other risk factors for HIV infection. Fifteen out of 78 (19.2%) female partners and one out of eighteen (5.5%) male partners were seropositive for HIV antibody. All couples had practised vaginal intercourse. Seropositive female partners did not differ significantly from seronegative partners with regard to length of relationship, number of acts of vaginal intercourse, other sexual practices, stage of clinical disease in the index case, or numbers of other sexual partners in the last five years. In two women, seroconversion was documented after one act of unprotected sexual intercourse. The majority of infected female partners (eight out of 15) had sexual relationships with men who were asymptomatic and did not practice anal intercourse. Biological factors such as variability in infectivity of the index case and susceptibility of the contact, as well as behavioural variables may be important in determining transmission. 相似文献
60.
Megan R. Schwarzman Janet M. Ackerman Shanaz H. Dairkee Suzanne E. Fenton Dale Johnson Kathleen M. Navarro Gwendolyn Osborne Ruthann A. Rudel Gina M. Solomon Lauren Zeise Sarah Janssen 《Environmental health perspectives》2015,123(12):1255-1264