The purpose of this study was to determine the role of radiation-induced expression of c-jun and c-fos in radiation-induced apoptosis of cells of the Jurkat T-cell line. Doses of 10-20 Gy caused a massive number of cells to undergo apoptosis within the first 24 h. This was accompanied by extensive increases in c-jun mRNA levels and moderate increases in c-fos levels, both occurring at the time of onset of internucleosomal DNA fragmentation. Increased c-jun and c-fos expression was maximum at 8 h after irradiation with a 10-fold increase in c-jun and a 2-fold increase in c-fos mRNA levels. In comparison, stimulation of the Jurkat cells with PMA resulted in rapid induction of c-jun and c-fos within 1 h. The late induction of c-jun and c-fos was not preceded by induction of tumor necrosis factor-alpha (TNF-alpha) or the bifunctional repair endonuclease and nuclear redox factor Ref-1; rather a slow decrease in Ref-1 mRNA levels was found over the first 24 h. Our results showed that radiation-induced c-jun and c-fos expression is a late response in Jurkat cells, and is most likely a secondary effect not necessary for radiation-induced apoptosis. Furthermore, apoptosis was induced by the RNA synthesis inhibitor actinomycin D, which does not induce c-jun or c-fos expression. This demonstrates that massive late induction of c-jun and c-fos is not a general requirement for apoptosis in Jurkat cells.

Apoptosis↗

PubMed1996

Nasopharyngeal adenoid cystic carcinoma: five new cases and a literature review.

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare tumour, and its mainstay treatment is different from adenoid cystic carcinoma arising from another head and neck region. In this study, we analyzed 20 cases of NACC with complete clinical information, 5 from Chang Gung Memorial Hospital and 15 from the literature review. RESULTS: The time interval between first symptom and treatment ranged from 2 weeks to 8 years, with a median of 24 months. Compared with usual nasopharyngeal carcinoma, NACC has higher incidence of cranial nerve involvement (55%) and lower incidence of cervical adenopathy (15%). All patients were treated by radiotherapy and 6 patients received surgical treatment. The 5- and 10-year overall survival rates were 78% and 49.5%, respectively. Seven patients developed metastasis to lung or bone. After a minimum of 5 years' follow-up, the local control rate was 45.5% in patients receiving radiation dose > 70 Gy, and 28.6% in those receiving dose < or = 70 Gy, suggesting higher radiation dose is necessary to achieve better local control in NACC.

Adult↗

PubMed1995

Induction of acute phase gene expression by brain irradiation.

PURPOSE: To investigate the in vivo acute phase molecular response of the brain to ionizing radiation. METHODS AND MATERIALS: C3Hf/Sed/Kam mice were given midbrain or whole-body irradiation. Cerebral expression of interleukins (IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-gamma), tumor necrosis factors (TNF-alpha and TNF-beta), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), alpha 1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined. RESULTS: Levels of TNF-alpha, IL-1 beta, ICAM-1, EB22/5.3 and to a lesser extent IL-1 alpha and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen. CONCLUSIONS: The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances.

Animals↗

PubMed1995

Biomechanical evaluation of anterior thoracolumbar spinal instrumentation.

STUDY DESIGN: A biomechanical study was designed to assess relative construct stabilities of modern anterior thoracolumbar instrumentations in a calf spine model with an anterior and middle column defect. OBJECTIVES: The purpose is to compare the biomechanical stability of various anterior fixation devices in an unstable calf spine model. SUMMARY OF BACKGROUND DATA: Modern types of anterior thoracolumbar instrumentations evolved to either rods or plates. Biomechanical properties and comparative studies of these instrumentations are lacking. METHODS: Twenty fresh calf spines (L2-L5) were used for the biomechanical tests. L2 and L5 vertebrae were used to attach the loading and base frames, respectively. Specimens underwent nondestructive biomechanical tests performed using a three-dimensional motion measuring system. In each specimen, three different cases were tested: intact spine, anterior fixation with an interbody graft after total discectomy and endplate excision of L3-L4 disc, anterior fixation only without the graft. Four anterior fixators, University Anterior Plating System, the Kaneda device, the Z-plate, and Texas Scottish Rite Hospital system were used. Each device was tested on five specimens. A polymethylmethacrylate block was inserted into the disc space to simulate the interbody grafting, and a fixation device was implanted with axial compression. Rotational angles of the L3-L4 segment stabilized by a fixation device and graft were normalized by the corresponding angles of the intact specimen to study the overall stabilizing effects. RESULTS: With the interbody graft and fixation devices, all showed significant stabilizing effects in flexion, extension, and lateral bending. All devices restored axial rotation stability to intact specimen, but only the Kaneda device restored the torsional stability beyond the intact specimen. No statistical differences in stabilizing effects in axial rotation were found between any of the tested devices. When the graft was removed, the Kaneda device significantly decreased the motions in all directions compared with the intact motion, whereas the University plate decreased the motions in flexion, extension, and lateral bending. The Texas Scottish Rite Hospital system was found to reduce the flexion and lateral bending motions significantly, and Z-plate decreased lateral bending motions only. Stabilizing effects of the interbody graft were significant in lateral bendings for all devices. Additionally, the significant stabilizing role of the graft was noted in flexion and extension in Z-plate only. The graft did not significantly reduce the axial rotation motion in any instrumentations. CONCLUSIONS: Modern anterior instrumentations for the thoracolumbar spine, such as the Kaneda device, Texas Scottish Rite Hospital system, Z-plate, and University plate, restored the stability in all motions when an interbody graft was inserted. The stability of fixation devices revealed that the Kaneda device is the best, particularly in restoring the torsional stability. The information on the relative stability provided by different instrumentations should help the spine surgeon in choosing the appropriate instrumentation for the particular circumstance.

Analysis of Variance↗

PubMed1995

Western influences on Chinese sexuality: insights from a comparison of the sexual behavior and attitudes of Shanghai and Hong Kong freshmen at universities.

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Asia↗

PubMed1995

Modification of tumor microenvironment by cytokine gene transfer.

The tumor microenvironment is determined by the interactions between host and tumor cells, a process in which cytokines play a major role. We have used retroviral vectors to insert and express cytokine genes in tumor cells so as to induce predictable changes in the host cells that infiltrate tumors. This frequently caused changes in tumor cell phenotype through autocrine/intracrine pathways. We reasoned that cytokine-induced alterations in tumor cell phenotype and/or in infiltrating host cells might alter the in vitro and in vivo cellular response to irradiation. In the present paper we document some of the effects of expression of interleukin-6 (IL-6) and IL-7 genes in tumor cells in this regard. The studies support the hypothesis that cytokines may play a role in determining both intrinsic tumor radioresponsiveness and the tumor microenvironment and in these ways may influence in vivo tumor irradiation responses. Possible cytokine gene-mediated approaches to radiotherapy cancer are discussed.

Animals↗

PubMed1994

Radiosensitivity of ataxia-telangiectasia, X-linked agammaglobulinemia, and related syndromes using a modified colony survival assay.

We used a modified colony survival assay to measure the sensitivity to ionizing radiation of more than 50 lymphoblastoid cell lines from normal individuals and from patients with ataxia-telangiectasia, Nijmegen breakage syndrome variants, and X-linked agammaglobulinemia. All of these disorders are associated with an increased frequency of cancer. Lymphoblastoid cell lines from patients with ataxia-telangiectasia complementation groups A, C, D, and E; ATFresno; Nijmegen breakage syndrome variants V1 and V2; and X-linked agammaglobulinemia showed marked radiosensitivity, whereas ataxia-telangiectasia heterozygotes were similar to controls. Friedreich's ataxia is not associated with increased cancer risk; lymphoblastoid cell lines from two such patients showed normal radiosensitivity. Taken together, these results suggest that some forms of X-ray sensitivity and cancer susceptibility share a common mechanism, such as an enzyme that is necessary both for the repair of radiation damage to DNA and for gene rearrangements during V(D)J recombination.

Agammaglobulinemia↗

PubMed1994

Ataxia-telangiectasia: flow cytometric cell-cycle analysis of lymphoblastoid cell lines in G2/M before and after gamma-irradiation.

It has been estimated that 1 to 3% of the general population may be ataxia-telangiectasia (A-T) heterozygotes and hypersensitive to conventional doses of radiation. We attempted to identify heterozygotes by evaluating the proportion of cells in various phases of the cell cycle in response to irradiation. This was accomplished by using flow cytometry to study lymphoblastoid cell lines (LCLs) from 14 A-T homozygotes, 17 genotypic A-T heterozygotes, and 18 normal individuals, including 10 genotypic normals. The LCLs were exposed to 2-gRay radiation and were analyzed after 24 hr along with nonirradiated controls. The difference between the percentage of cells in G2/M with and without irradiation after 24 hr ranged, respectively, from: 12.0 to 31.5% (mean = 18.7 +/- 5.5) for A-T homozygotes; 6.7 to 19.3% (mean = 12.5 +/- 3.8) for A-T heterozygotes; and -1.5 to 12.4% (mean = 6.4 +/- 3.2) for normals. A cut-off region of 9.6 to 13.2% defined by one standard deviation above the mean for normals and one standard deviation below the mean for A-T homozygotes served as the grey zone between normals and A-T heterozygotes or homozygotes. Two of the 18 normals overlapped with the grey zone. Four of 17 heterozygotes were within the normal range; seven fell within the grey zone. This may reflect nongenetic variables, such as the status of the LCLs at the time of testing. Flow cytometry cell-cycle analysis on irradiated LCLs is a useful adjunctive test for establishing a diagnosis of A-T in questionable cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Ataxia Telangiectasia↗

PubMed1994

G2/M-phase arrest and release in ataxia telangiectasia and normal cells after exposure to ionizing radiation.

Cells from patients with ataxia telangiectasia (AT) are abnormal in their response to irradiation as judged by clonogenic survival and accumulation in G2 phase. The relationship of the results of these two assays, however, is still a matter of controversy. Flow cytometry was used to measure the distribution of cells in the phases of the cell cycle after 2 Gy irradiation in Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) and SV40-transformed fibroblasts. AT cells showed increased and prolonged accumulation in G2/M phase regardless of the cell type (lymphoblastoid or fibroblast) or complementation group (A, C or D). To test the hypothesis that prolonged accumulation of AT cells in G2 phase after irradiation was not simply a reflection of their radiosensitivity, we gave iso-survival radiation doses to SV40-transformed fibroblasts of two AT and one control cell lines. The two AT cell lines exited from the G2/M-phase block more slowly than control cells after each dose tested. This implies that prolonged accumulation in G2/M phase in AT cells is not directly related to radiosensitivity as measured by clonogenic survival, but that factors involved in the exit from G2 phase after irradiation may be abnormally regulated. We found that G2-phase arrest of AT cells did not necessarily result in a fatal consequence in the first cell cycle after irradiation. Furthermore, G2-phase arrest did not lead to detectable DNA fragmentation characteristic of apoptosis as judged by gel electrophoresis.

Ataxia Telangiectasia↗

PubMed1994

[Observation on the action of extractum semen Persicae on anti-fibrosis of liver].

It was observed that Extractum Semen Persicae acted obviously on hepatic fibrosis induced by CCl4. Through promoting the degradation of collagens type I, II, IV, VI and fibronectin, ESP has proved helpful in markedly reducing the fibrous septa composed of both collagenous and reticular fibers as well as in repairing the structure of hepatic tissues.

Amygdalin↗

PubMed1993

The influence of mode of dialysis pretransplantation on long-term renal allograft outcome.

To determine the influence of the need and the mode of dialysis prior to transplantation on long-term renal allograft survival and subsequent renal function, all 662 consecutive cyclosporine-treated renal transplants (484 cadaver and 178 living-related donors), performed between 1983 and 1989 were retrospectively analyzed. Recipients were divided into 3 groups as follows: group I and II recipients underwent hemodialysis and peritoneal dialysis, respectively, prior to transplantation; group III patients were transplanted without dialysis. All groups were similar with respect to demographic and immunologic characteristics, apart from a higher proportion of diabetic and White patients in both cadaver and living-related group III recipients and a fewer number of blood transfusions among living-related group III recipients. A trend toward a decreased incidence of dialysis dependence in the early posttransplant period was noted among cadaver donor recipients in group III (20%) when compared to group I and II patients (36% and 26%, respectively). The incidence of rejection episodes was similar in all groups. No difference in 1- and 5-year patient survival was noted among all recipient groups. Actual 1-year graft survivals in groups I, II, and III were similar (73%, 72%, and 74%, respectively, for cadaver donor; and 86%, 89%, and 91%, respectively for living-related donor recipients). Likewise, actuarial 5-year graft survivals were not significantly different (53%, 51%, and 67%, respectively, for cadaver donor; and 75%, 69%, and 82%, for living-related donor recipients). Renal function, as assessed by serum creatinine concentration, was similar and stable in all recipient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

PubMed1993

Influence of donor and recipient age on renal allograft survival time.

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Actuarial Analysis↗