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43.
Comparison of total alkaline phosphatase and three assays for bone-specific alkaline phosphatase in childhood and adolescence 总被引:2,自引:0,他引:2
F Rauch B Middelmann M Cagnoli KM Keller E Schönau 《Acta paediatrica (Oslo, Norway : 1992)》1997,86(6):583-587
We compared serum levels of total alkaline phosphatase (TAP) and bone-specific alkaline phosphatase (BAP) as determined by three different assays (lectin affinity electrophoresis, immunoradiometric assay, enzyme-linked immunosorbent assay) in subjects aged 5–20 years suffering from X-linked hypophosphatemic rickets ( n = 14), chronic renal failure ( n = 10) and chronic cholestatic liver disease ( n = 16). Results were compared to controls of the same age and were expressed as standard deviation scores (SDS). TAP correlated significantly with BAP ( r > 0.9 for each assay; p <0.001) in controls. In children with cholestatic diseases, TAP (median SDS + 2.0) was elevated, but BAP, as measured by the electrophoretic assay, was within the reference range for most patients (median SDS: -0.4; p = 0.003 for the difference between the median SDS of TAP and BAP). In contrast, results for BAP as determined by the two immunoassays were not significantly different from TAP in any of the three patient groups ( p > 0.05 in each group for both assays). In this study, the two immunoassays did not have a detectable advantage over lectin affinity electrophoresis in the determination of BAP. 相似文献
44.
Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma 总被引:1,自引:0,他引:1
Presnell SC; Borchert KM; Glover WJ; Gregory CW; Mohler JL; Smith GJ 《Carcinogenesis》1998,19(4):585-590
The Dunning H rat prostate tumor (R3327H) is a widely used experimental
model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been
characterized as androgen-sensitive, androgen-receptor (AR) positive,
prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To
date, the tumor has been maintained by serial passage in vivo because of
the lack of an in vitro cell line that retains the characteristics of the
in vivo tumor. The objective of the present study was to establish a
propagable cell line from R3327H adenocarcinoma that maintained androgen
sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in
vivo R3327H tumor was dissociated with collagenase and placed into
Richter's improved media (with supplements). A cytokeratin-positive
epithelial cell line (HUNC- E) and a vimentin-positive stromal cell line
(HUNC-S) were generated from the primary culture, subcultured continuously
for >300 days, and passaged >50 times. Survival of the HUNC-E cell
line in vitro depended on several media supplements, including
nicotinamide, insulin, transferrin, selenium and epidermal growth factor
(EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the
culture period, as confirmed by immunocytochemistry and Western blot
analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT)
to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent
growth and PSA production, which demonstrated the androgen-sensitive nature
of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1
ratio and introduced subcutaneously into syngeneic male hosts, tumors
formed in 2/3 animals with an average latency of 7 months. RT-PCR and
immunocytochemical characterization of the HUNC cell lines revealed that
the cells expressed several growth factors and their cognate receptors,
including HGF, TGF-alpha and the TGF-betas, indicating the establishment of
potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S
CaP cell lines, which retain the characteristics of the epithelial and
stromal components of the in vivo R3327H tumor, will allow a more thorough
and informative molecular and biological analysis of prostatic
adenocarcinoma.
相似文献
45.
E. J. Estlin L. Lashford S. Ablett L. Price R. Gowing A. Gholkar J. Kohler I. J. Lewis B. Morland C. R. Pinkerton M. C. Stevens M. Mott R. Stevens D. R. Newell D. Walker C. Dicks-Mireaux H. McDowell P. Reidenberg P. Statkevich A. Marco V. Batra M. Dugan A. D. Pearson 《British journal of cancer》1998,78(5):652-661
A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen of 20 patients who had not received prior craniospinal irradiation or nitrosourea therapy were evaluable. Myelosuppression was dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one of six patients receiving 1000 mg m(-2) per cycle, and two of four patients treated at 1200 mg m(-2) per cycle. Therefore, the maximum-tolerated dose (MTD) was 1000 mg m(-2) per cycle. The MTD was not defined for children with prior craniospinal irradiation because of poor recruitment. Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose. Responses (CR and PR) were seen in two out of five patients with high-grade astrocytomas, and one patient had stable disease. One of ten patients with diffuse intrinsic brain stem glioma achieved a long-term partial response, and a further two patients had stable disease. Therefore, the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle. Further evaluation in diffuse intrinsic brain stem gliomas and other high-grade astrocytomas is warranted. 相似文献
46.
Hazelton TR Newell JD Cook JL Huitt GA Lynch DA 《AJR. American journal of roentgenology》2000,175(2):413-416
OBJECTIVE: The purpose of this report is to describe helical and high-resolution CT findings in 14 patients with pulmonary infection caused by Mycobacterium chelonae, a nontuberculous mycobacterial species that has become increasingly recognized as a rare but significant cause of chronic lung infection in immunocompetent patients. CONCLUSION: Bronchiectasis, nodules, and consolidation are the most common CT features of M. chelonae pulmonary infection. Cavities are less common. These CT findings resemble those reported for Mycobacterium avium complex. In this study, M. chelonae pulmonary infection occurred exclusively in middle-aged and older women. 相似文献
47.
IMPLICATIONS: We report the successful use of the laryngeal mask airway for percutaneous endoscopic gastrostomy in an adult patient with a known difficult airway and severe cerebral palsy. 相似文献
48.
Monica S Vavilala Lorri A Lee Krishna Boddu Elizabeth Visco David W Newell Jerry J Zimmerman Arthur M Lam 《Pediatric critical care medicine》2004,5(3):257-263
OBJECTIVE: The aims of this study were to document the incidence of impaired cerebral autoregulation in children with traumatic brain injury using transcranial Doppler ultrasonography and to examine the relationship between autoregulatory capacity and outcome in children following traumatic brain injury. DESIGN: Prospective cohort study. SETTING: Harborview Medical Center (level I pediatric trauma center) in Washington state. PATIENTS: Thirty-six children <15 yrs old with traumatic brain injury: Glasgow Coma Scale score <9 (n = 12, group 1), Glasgow Coma Scale score 9-12 (n = 12, group 2), and Glasgow Coma Scale score 13-15 (n = 12, group 3). INTERVENTIONS: Cerebral autoregulation testing was conducted during extracranial surgery. Mean middle cerebral artery flow velocities were measured using transcranial Doppler as mean arterial pressure was increased to whichever variable was greater: 20% above baseline or a set value (80 mm Hg for <9 yrs and 90 mm Hg for 9-14 yrs). Autoregulatory capacity was quantified by the Autoregulatory Index. Autoregulatory Index <0.4 was considered impaired cerebral autoregulation. Discharge outcome using the Glasgow Outcome Scale score was considered good if the Glasgow Outcome Scale score was > or =4. MEASUREMENTS AND MAIN RESULTS: Twenty-four (67%) of 36 children had an Autoregulatory Index > or =0.4. The incidence of impaired cerebral autoregulation was 42% (five of 12) in group 1, 42% (five of 12) in group 2, and 17% (two of 12) in group 3. Ten (42%) of the 24 children with intact cerebral autoregulation had a good outcome compared with only one of 12 (8%) children with impaired cerebral autoregulation (p =.04). Six of 12 (50%) children with impaired cerebral autoregulation had hyperemia compared with one of 24 (4%) children with intact cerebral autoregulation (p <.01). Hyperemia was associated with poor outcome (p =.01). CONCLUSIONS: The incidence of impaired cerebral autoregulation was greatest following moderate to severe traumatic brain injury. Impaired cerebral autoregulation was associated with poor outcome. Hyperemia was associated with impaired cerebral autoregulation and poor outcome. 相似文献
49.
50.
E Ruth Plummer Mark R Middleton Christopher Jones Anna Olsen Ian Hickson Peter McHugh Geoffrey P Margison Gail McGown Mary Thorncroft Amanda J Watson Alan V Boddy A Hilary Calvert Adrian L Harris David R Newell Nicola J Curtin 《Clinical cancer research》2005,11(9):3402-3409
PURPOSE: Temozolomide, a DNA methylating agent used to treat melanoma, induces DNA damage, which is repaired by O6-alkylguanine alkyltransferase (ATase) and poly(ADP-ribose) polymerase-1 (PARP-1)-dependent base excision repair. The current study was done to define the effect of temozolomide on DNA integrity and relevant repair enzymes as a prelude to a phase I trial of the combination of temozolomide with a PARP inhibitor. EXPERIMENTAL DESIGN: Temozolomide (200 mg/m2 oral administration) was given to 12 patients with metastatic malignant melanoma. Peripheral blood lymphocytes (PBL) were analyzed for PARP activity, DNA single-strand breakage, ATase levels, and DNA methylation. PARP activity was also measured in tumor biopsies from 9 of 12 patients and in PBLs from healthy volunteers. RESULTS: Temozolomide pharmacokinetics were consistent with previous reports. Temozolomide therapy caused a substantial and sustained elevation of N7-methylguanine levels, a modest and sustained reduction in ATase activity, and a modest and transient increase in DNA strand breaks and PARP activity in PBLs. PARP-1 activity in tumor homogenates was variable (828 +/- 599 pmol PAR monomer/mg protein) and was not consistently affected by temozolomide treatment. CONCLUSIONS: The effect of temozolomide reported here are consistent with those documented in previous studies with temozolomide and similar drug, dacarbazine, demonstrating that a representative patient population was investigated. Furthermore, PARP activity was not inhibited by temozolomide treatment and this newly validated pharmacodynamic assay is therefore suitable for use in a proof-of-principle phase I trial a PARP-1 inhibitor in combination with temozolomide. 相似文献