Radiologic findings of the lumbar spine in patients with rheumatoid arthritis,and a review of pathologic mechanisms

We have analyzed the radiologic findings on the lumbar spine and the clinical symptoms in patients with rheumatoid arthritis (RA). A total of 106 patients who fulfilled the revised criteria of the American Rheumatism Association were subjected. All of the patients were asked to fill out a questionnaire about the existence of low back pain, leg pain, and leg numbness. Radiologic features of the lumbar spine, including scoliosis, spondylolisthesis, disc space narrowing, endplate erosion, osteophyte, and osteoporosis, were checked. Radiographs of the cervical spine were also taken. The clinical background of RA, such as mutilating disease or not, was assessed. Forty-two patients (40%) had the symptoms of low back pain. Abnormal radiologic findings in lumbar spine were detected in 57%. The prevalence of clinical symptoms tended to be higher in the patients with endplate erosion. Forty-two percent of the patients had both lumbar and cervical lesions. The prevalence of lumbar lesion was not high in the mutilating type of RA, except for facet erosion and severe osteoporosis. The patients with pulse steroid therapy revealed a higher prevalence of vertebral fracture. From these results, we concluded that lumbar lesions were frequently observed in patients with RA. The possibility of lumbar lesions as well as the lesions in the cervical spine and peripheral joints should be examined in patients with RA.     

A novel WT1 gene mutation associated with wilms' tumor and congenital male genitourinary malformation

WT1 is located on the short arm of human chromosome 11 and consists of 10 coding exons. Mutations of this gene have been reported to be the cause of Wilms' tumor, congenital male genitourinary malformations, and/or renal disorders. We describe here a novel WT1 gene mutation, i.e. a point mutation at intron 7 (+2) in both the tumor and the germline cells of a patient with Wilms' tumor and congenital male genitourinary malformation, but without renal disorder. The position of the mutation is at a splice donor site of intron 7, which causes the splicing out of exon 7 and generates a truncated protein. This type of mutation in the WT1 zinc finger domain has not been reported before. The mutation is of paternal origin and is heterozygous in the germline cells. In the tumor cells, however, the maternal allele is largely lost, from 11p12 to 11p15, which results in maternal loss of heterozygosity. These results, together with the data from previous reports, suggest that WT1 may function in gonadogenesis, nephrogenesis, and Wilms' tumor tumorigenesis.     

Clinical features of extraforaminal lumbar disc herniation based on the radiographic location of the dorsal root ganglion

STUDY DESIGN: The relations between the location of the dorsal root ganglion and pre- and postoperative symptoms were reviewed retrospectively in 27 patients who underwent radiculography and posterior discectomy. OBJECTIVES: To evaluate the clinical features and surgical outcome of extraforaminal lumbar disc herniation based on the location of dorsal root ganglion. SUMMARY OF BACKGROUND DATA: The location of dorsal root ganglia has been reported to be correlated with a variety of radicular symptoms. Extraforaminal lumbar disc herniation has several specific clinical features, one of which is severe radicular pain. However, there is no report in the literature on the association between the location of the dorsal root ganglia and the severity of the symptoms of extraforaminal lumbar disc herniation. METHODS: The radiographic location of the dorsal root ganglion of each compressed nerve root was determined by preoperative direct radiculograms. All patients were classified into the following three groups according to the location of dorsal root ganglion: intraspinal, intraforaminal, and extraforaminal. The incidences of these locations were 5 of 27 (18.5%), 15 of 27 (55.5%), and 7 of 27 (25.9%), respectively. The relation between the location of the dorsal root ganglion and clinical parameters such as the level of the compressed nerve root, the degree of limitation on straight leg raising test, the severity of the pre- and postoperative subjective symptoms (leg pain, low back pain, and walking capacity), clinical signs (sensory and motor disturbance), and the recovery rate were investigated. RESULTS: The degree of limitation on the straight leg raising test in the extraforaminal group tended to be low, compared with that in the intraspinal and intraforaminal groups. Low back pain in the extraforaminal group was more severe than that in the intraspinal and intraforaminal groups. Preoperative leg pain in the extraforaminal group was significantly more severe that that in the intraspinal group, and the walking capacity in the extraforaminal group tended to be lower than that in the intraspinal and intraforaminal groups. No significant differences were found between the location of dorsal root ganglion and the preoperative sensory or motor disturbance and surgical outcomes. CONCLUSION: The location of the dorsal root ganglion might influence the severity of radicular symptoms (pain and walking distance tolerance) in patients with extraforaminal lumbar disc herniation.     

Differential Effect of TPA on Cell Growth and Epstein-Barr Virus Reactivation in Epithelial Cell Lines Derived from Gastric Tissues and B Cell Line Raji

We characterized the cell growth and Epstein-Barr virus (EBV) reactivation for EBV infected epithelial cell lines, GT38, GT39, and GTC-4 using 12-O-tetradecanoylphorbol-13-acetate (TPA). These cell lines grew similarly in liquid medium, and formed colonies in soft agar. The cell growth was inhibited with TPA, dose-dependently in liquid medium. The colony formation was enhanced with low concentrations of TPA, but was inhibited with high concentrations. The latent EBV was reactivated with high concentrations of TPA as shown by the expression of EBV BZLF1 gene product ZEBRA. The effects of TPA on GTC-4 were compared with a Burkitt's lymphoma cell line Raji. The mode of actions of TPA in GTC-4 was different from Raji in terms of cell growth and EBV reactivation. The effective concentrations of TPA for cell growth inhibition and EBV reactivation were higher in Raji than GTC-4. Cell cycle analysis showed that TPA (20 ng/ml) induced cell cycle arrest to Raji but not to GTC-4; however, the rate of trypan blue stained cells increased in the TPA treated GTC-4 but not Raji. These results demonstrated that TPA affects differentially for the stimulation and inhibition of cell growth, and also EBV reactivation depends on TPA concentrations and cell types.     

Low-dose cytarabine-induced hepatic and renal dysfunction in a patient with myelodysplastic syndrome.

We report a 49-year-old female patient with secondary myelodysplastic syndrome who developed liver dysfunction and acute renal failure caused by low-dose cytosine arabinoside (Ara-C) therapy. Treatment of low-dose Ara-C has widely been used for acute myelogeous leukemia and myelodysplastic syndrome, and it is thought to be a low toxicity except for myelosuppression. The patient complained of a transient adverse reaction in the second and third course of therapy. This rare case indicates that careful observation should be carried out during low-dose Ara-C therapy in view of allergic reactions.     

Cisplatin-resistant HeLa Cells Are Resistant to Apoptosis via p53-dependent and -independent Pathways

Since HeLa cells possess very little functional p53 activity, they could be originally resistant to genotoxic stress-induced apoptosis. Therefore, it is likely that the drug-resistant cells derived from HeLa cells are more resistant to apoptosis. The aim of this study was to determine whether cisplatin-resistant cells derived from HeLa cells have an apoptosis-resistant phenotype. A cisplatin-resistant cell subline, HeLa/CDDP cells, showed a 19-fold resistance to cisplatin compared with the parent cells. The subline showed a collateral sensitivity to paclitaxel. An equitoxic dose (IC₅₀) of cisplatin produced DNA fragmentation in HeLa cells but not in HeLa/CDDP cells. Transfection of wild-type p53 gene enhanced the cytotoxicity of cisplatin and cisplatin-induced apoptosis in HeLa cells but not in HeLa/CDDP cells, although it caused p53 overexpression in both cell lines. The expression of caspase 1 (interleukin-1β-converting enzyme, ICE) mRNA and the overexpression of bax protein were observed only in HeLa cells. Paclitaxel-induced DNA fragmentation appeared less in HeLa/CDDP cells than in HeLa cells. p53 gene transfection did not affect the extent of DNA fragmentation in either cell line, suggesting that paclitaxel may induce p53-independent apoptosis. These findings suggest that HeLa/CDDP cells may have an acquired phenotype that is resistant to p53-dependent and -independent apoptosis.     

Clinical effects of low-dose Ara-C in acute nonlymphocytic leukemia and myelodysplastic syndromes

Forty-eight patients with acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndromes (MDS) were treated with low-dose Ara-C regimen (LDAC) (10 mg/m2 or 10 mg/body subcutaneously every 12 hours). Complete remission (CR) was obtained in sixteen patients (33%) and partial remission (PR) in six (16%). Seven of eight patients with hypoplastic leukemia entered CR. However, LDAC was not effective in MDS and ANLL developing from MDS. The rate of CR was 20% in relapsed or refractory ANLL. Relapse was occurred in thirteen patients until now. The median duration of remission was 7 months (range: 3-20 months). Seven of the sixteen patients who achieved CR were received LDAC at the same dose for 10 days every month as a maintenance therapy. The duration of CR of these patients was shown to be longer than that of the patients without any maintenance therapy. Myelosuppression was observed in nearly all of them and the other clinical findings including cytogenetic analysis indicated cytotoxicity rather than differentiation as the mechanism of LDAC. LDAC was effective especially in hypoplastic leukemia and the maintenance therapy was found to prolong the duration of CR.