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111.
Role of insulin-like growth factor binding proteins in 1alpha,25-dihydroxyvitamin D(3)-induced growth inhibition of human prostate cancer cells 总被引:2,自引:0,他引:2
BACKGROUND: The mechanisms underlying 1alpha,25-dihydroxyvitamin D(3) (1,25D)-induced growth inhibition of human prostate cancer cells have not been fully elucidated. To determine whether alterations in the insulin-like growth factor (IGF) signaling axis are associated with 1,25D-induced growth inhibition, we examined the ability of 1,25D to regulate expression of IGF binding proteins (IGFBPs) in human prostate cancer cell lines. METHODS: Northern and Western blot analyses were used to detect 1,25D-induced alterations in IGFBP expression. Additional in vitro studies were performed to determine the role of IGFBP-3 in 1,25D-induced growth inhibition. RESULTS: 1,25D decreased mRNA levels of the growth stimulatory IGFBP-2 and induced IGFBP-3 mRNA in LNCaP and C4-2 cells. 1,25D treatment also increased secreted IGFBP-3 protein levels in prostate cancer cell lines sensitive to 1,25D growth inhibition but had little effect on IGFBP-3 expression in 1,25D-resistant DU145 cells. However, recombinant IGFBP-3 had only a minor effect on LNCaP cell growth in the presence of serum. Furthermore, siRNA duplexes that reduced IGFBP-3 expression did not alter 1,25D growth inhibition in either LNCaP or PC-3 cell lines grown in serum-containing media. CONCLUSIONS: Our studies indicate 1,25D-induced up-regulation of IGFBP-3 is not required for the growth inhibitory effects of 1,25D in prostate cancer cells grown in serum-containing media. 相似文献
112.
Analysis and management of chronic testicular pain 总被引:3,自引:0,他引:3
A total of 45 patients was seen in consultation between May 1980 and April 1989 for chronic unilateral or bilateral orchialgia, defined as intermittent or constant testicular pain 3 months or longer in duration that significantly interferes with the daily activities of the patient so as to prompt him to seek medical attention. We analyzed 34 patients available for followup in terms of socioeconomic parameters, etiology and duration of pain, associated urological symptomatology, specific treatment and results of therapy. Of the patients 31 underwent surgical treatment after failing medical management (24 orchiectomies, 10 epididymectomies, 5 orchiopexies and 1 hydrocelectomy). Of 10 patients who underwent epididymectomy 9 underwent subsequent orchiectomy as definitive treatment. Of 15 patients who underwent inguinal orchiectomy 11 (73%) reported complete relief of pain, while 4 had partial relief. Of the 9 patients who underwent scrotal orchiectomy 5 (55%) reported complete relief of pain, 3 had partial relief and 1 denied improvement. On the basis of these results we recommend inguinal orchiectomy as the procedure of choice for the management of chronic testicular pain when conservative measures are unsuccessful. 相似文献
113.
Braffman BH; Coleman BG; Ramchandani P; Arger PH; Nodine CF; Dinsmore BJ; Louie A; Betsch SE 《Radiology》1994,190(3):797
114.
Oda A; Miyakawa Y; Druker BJ; Ishida A; Ozaki K; Ohashi H; Wakui M; Handa M; Watanabe K; Okamoto S; Ikeda Y 《Blood》1996,88(11):4304-4313
Platelet functions such as aggregation and clot retraction are often abnormal in chronic mylogenous leukemia (CML) patients. However, the molecular mechanisms of these altered functions are unknown. As expression of the p210bcr-abl oncogene product, a constitutively active tyrosine kinase, is known to have an essential role in the pathogenesis of CML and tyrosine phosphorylation is intimately involved in various aspects of platelet activation, we examined the pattern of protein tyrosine phosphorylation in platelets from 15 CML patients by immunoblotting with a monoclonal antiphosphotyrosine antibody (4G10). Before and after stimulation with thrombin, the only consistent difference between normal and CML platelets was the presence of a tyrosine phosphorylated protein with a relative molecular weight of 39 kD. This tyrosine phosphorylated protein was identified as crid, an SH2, SH3 containing adapter protein. Thus, as previously demonstrated for neutrophils from CML patients, tyrosine phosphorylation of p39crkl persists in mature platelets. No tyrosine phosphorylation of crid was detected following stimulation with thrombin in normal platelets. However, crkl became incorporated into the Triton X-100 insoluble residue following thrombin stimulation in a manner dependent on platelet aggregation. Further, we found that crkl is an endogenous substrate for calpain, a protease that may be involved in postaggregation signaling processes. This suggests that crkl may be involved in the reorganization of the cytoskeleton during normal platelet aggregation and its tyrosine phosphorylation in CML platelets may contribute to the abnormal platelet function in CML patients. Finally, we found that thrombopoietin induces tyrosine phosphorylation of crk1 in normal platelets and FDCP cells genetically engineered to express human c-Mpl. This suggests that crk1 can be phosphorylated by a kinase other than p210bcr-abl and that crk1 may have a role in signaling by thrombopoietin. 相似文献
115.
MJ McKinley RM McAllen GL Pennington A. Smardencas RS Weisinger BJ Oldfield 《Clinical and experimental pharmacology & physiology》1996,23(Z3):99-104
- 1 Autoradiographic binding studies have shown that the AT1 receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT1 receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
- 2 While there are differences between species, AT2 receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
- 3 Circulating AngII acts on AT1 receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
- 4 Centrally administered AngII may act on AT1 receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
- 5 Recent evidence shows that centrally administered AT1 antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
- 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT1 receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.
116.
We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl- GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma. 相似文献
117.
Thrombopoietin primes human platelet aggregation induced by shear stress and by multiple agonists 总被引:6,自引:2,他引:6
Oda A; Miyakawa Y; Druker BJ; Ozaki K; Yabusaki K; Shirasawa Y; Handa M; Kato T; Miyazaki H; Shimosaka A; Ikeda Y 《Blood》1996,87(11):4664-4670
Recombinant thrombopoietin has been reported to stimulate megakaryocytopoiesis and thrombopoiesis and it may be quite useful to treat patients with low platelet counts after chemotherapy. As little is known regarding the possible activation of platelets by thrombopoietin, we examined the effects of thrombopoietin on platelet aggregation induced by shear stress and various agonists in native plasma. Using hirudin as an anticoagulant, thrombopoietin (1 to 100 ng/mL) enhanced platelet aggregation induced by 2 micromol/L adenosine- diphosphate (ADP) in a dose dependent fashion. The enhancement was not affected by treatment of platelets with 1 mmol/L aspirin plus SQ-29548 (a thromboxane antagonist, 1 micromol/L) but was inhibited by a soluble form of the thrombopoietin receptor, suggesting that the enhancement was mediated by the specific receptors and does not require thromboxane production. Epinephrine (1 micromol/L), which does not induce platelet aggregation in hirudin platelet rich plasma (PRP), did so in the presence of thrombopoietin (10 ng/mL). Thrombopoietin (10 ng/mL) also enhanced or primed platelet aggregation induced by collagen (0.5 micron.mL),. thrombin, serotonin, and vasopressin. Thrombopoietin does not induce any rise in cytosolic ionized calcium concentration nor activation of protein kinase C, as estimated by phosphorylation of preckstrin, indicating that the priming effects of thrombopoietin does not require those processes. The ADP- or thrombin-induced rise in cytosolic ionized calcium concentration was not enhanced by thrombopoietin (100 ng/mL). Further, shear (ca. 90 dyn/cm2)-induced platelet aggregation was also potentiated by thrombopoietin. The priming effect on epinephrine-induced platelet aggregation in hirudin PRP was unique to thrombopoietin, with no effects seen using interleukin-6 (IL-6), IL-11, IL-3, erythropoietin, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, or c-kit ligand. These data indicate that monitoring of platelet functions may be necessary in the clinical trials of thrombopoietin. 相似文献
118.
Maria BJ Chun David S Jackson Susan Y Lin Elyse R Park 《Hawai'i Journal of Medicine & Public Health》2010,69(12):289-293
The need for physicians formally trained to deliver care to diverse patient populations has been widely advocated. Utilizing a validated tool, Weissman and Betancourt''s Cross-Cultural Care Survey, the aim of this current study was to compare surgery and family medicine residents'' perceptions of their preparedness and skillfulness to provide high quality cross-cultural care. Past research has documented differences between the two groups'' reported impressions of importance and level of instruction received in cross-cultural care. Twenty surgery and 15 family medicine residents participated in the study. Significant differences were found between surgery and family medicine residents on most ratings of the amount of training they received in cross-cultural skills. Specifically, family medicine residents reported having received more training on: 1) determining how patients want to be addressed, 2) taking a social history, 3) assessing their understanding of the cause of illness, 4) negotiating their treatment plan, 5) assessing whether they are mistrustful of the health care system and/or doctor, 6) identifying cultural customs, 7) identifying how patients make decisions within the family, and 8) delivering services through a medical interpreter. One unexpected finding was that surgery residents, who reported not receiving much formal cultural training, reported higher mean scores on perceived skillfulness (i.e. ability) than family medicine residents. The disconnect may be linked to the family medicine residents'' training in cultural humility — more knowledge and understanding of cross-cultural care can paradoxically lead to perceptions of being less prepared or skillful in this area. 相似文献
119.
George Groeneweg Frank JPM Huygen Sjoerd P Niehof Feikje Wesseldijk Johannes BJ Bussmann Fabienne C Schasfoort Dirk L Stronks Freek J Zijlstra 《BMC musculoskeletal disorders》2008,9(1):143
Background
This double-blind, randomized, controlled trial investigated the effect of the phosphodiesterase-5 inhibitor tadalafil on the microcirculation in patients with cold Complex Regional Pain Syndrome (CRPS) in one lower extremity. 相似文献120.
Magnetic resonance (MR) imaging was performed on 14 patients with histologically proved osteosarcoma (mean age, 14.4 years). There was excellent correlation of intramedullary tumor extent as determined with MR imaging and pathologic examination (r = 99%). This was facilitated by the presence of a chemical shift artifact at the tumor-marrow interface on the T1-weighted images. The correlation between CT and pathologic findings was not as good (r = 84%). In a single patient, however, a 10-cm length of sclerotic bone was incorrectly interpreted as being tumor. If this case is excluded, the correlation between CT and pathologic findings improves significantly (r = 96%). T2-weighted images were optimal in demonstrating soft-tissue bulk and breach of the epiphysis or cortex. Vascular involvement was also readily defined. The T2 value of the tumor soft-tissue component decreased in patients who were deemed to have responded well to therapy. Two patients with very high T2 values after chemotherapy developed wide-spread metastatic disease and died. Phosphorus-31 MR spectroscopy of five patients with osteosarcoma showed elevated levels of phosphomonoesters (PMEs), inorganic phosphate (Pi), and phosphodiesters (PDEs). PME and PDE peak areas decreased in three patients after chemotherapy, while Pi peak areas increased. 相似文献