Fidgetin-like 1 gene inhibited by basic fibroblast growth factor regulates the proliferation and differentiation of osteoblasts.

The FIGNL1 gene was proven to be a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). In this in vitro study, the AAA proteins inhibited osteoblast proliferation and stimulated osteoblast differentiation. We showed that FIGNL1 may play some regulatory role in osteoblastogenesis. INTRODUCTION: The fidgetin-like 1 (FIGNL1) gene encodes a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). Although the FIGNL1 protein localizes to both the nucleus and cytoplasm, the function of FIGNL1 remains unknown. In a previous study, we identified several genes that mediate the anabolic effects of basic fibroblast growth factor (bFGF) on bone by using microarray data. FIGNL1 was one of the genes that downregulated >2-fold in MC3T3-E1 cells after treatment with bFGF. Therefore, this study was aimed to identify and confirm the function of FIGNL1 on osteoblastogenesis. MATERIALS AND METHODS: We examined the effect of the FIGNL1 gene on proliferation, differentiation, and apoptosis in mouse osteoblast cells (MC3T3-E1 and mouse primary calvarial cells) using flow cytometry, RT-PCR, cell proliferation assay, and cell death assay. MC3T3-E1 cells and mouse calvarial cells were transfected with small interfering RNA (siRNA) directed against the FIGNL1 or nontargeting control siRNA and examined by cell proliferation and cell death assays. Also, FIGNL1 was fused to enhance green fluorescent protein (EGFP), and the EGFP-fused protein was transiently expressed in MC3T3-E1 cells. RESULTS: Reduced expression of FIGNL1 by bFGF and TGF-beta1 treatment was verified by RT-PCR analysis. Overexpression of FIGNL1 reduced the proliferation of MC3T3-E1 and calvarial cells, more than the mock transfected control cells did. In contrast, siFIGNL1 transfection significantly increased the proliferation of osteoblasts, whereas overexpression of FIGNL1 did not seem to alter apoptosis in osteoblasts. Meanwhile, overexpression of FIGNL1 enhanced the mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN) in osteoblasts. In contrast, siFIGNL1 decreased the expression of ALP and OCN. A pEGFP-FIGNL1 transfected into MCT3-E1 cells had an initially ubiquitous distribution and rapidly translocated to the nucleus 1 h after bFGF treatment. CONCLUSIONS: From these results, we proposed that FIGNL1, a subfamily member of the AAA family of proteins, might play some regulatory role in osteoblast proliferation and differentiation. Further analyses of FIGNL1 will be needed to better delineate the mechanisms contributing to the inhibition of proliferation and stimulation of osteoblast differentiation.     

The immunomodulatory effects of 3-monochloro-1,2-propanediol on murine splenocyte and peritoneal macrophage function in vitro.

3-Monochloro-1,2-propanediol (MCPD) is a well-known by-product of acid-hydrolyzed soy sauce during its manufacturing process. MCPD has been reported genotoxic in vitro, and reproductive toxicity and carcinogenicity in rats. To evaluate the immunomodulatory effect of MCPD on murine splenocyte and macrophage in vitro, we investigated splenocyte blastogenesis by concanavalin A (Con A), anti-CD3, and lipopolyssacharide (LPS), the production of cytokines from splenocyte, and the activity of mouse peritoneal macrophages. There was a significant decrease in lymphocyte blastogenesis to Con A or anti-CD3 at subtoxic dose of MCPD. A significant decrease in splenocyte blastogenesis to LPS was also observed. The production level of interferon (IFN)-gamma on splenocyte culture with Con A was significantly reduced at the higher concentration than 1.0mM of MCPD. The levels of interleukin (IL)-4 and IL-10 were also decreased at high concentrations of MCPD. There was a significant decrease in production of nitric oxide (NO) by peritoneal macrophages treated with MCPD. MCPD also inhibits tumor necrosis factor (TNF)-alpha production of stimulated macrophages. These results indicate that MCPD might be able to reduce the functionality of lymphocytes and peritoneal macrophages in vitro.     

Expression of interleukin-6 in polymorphic reticulosis--immunohistochemical study of 5 cases.

Peripheral T cell lymphoma encompasses lymphomas with a variety of histologic appearances and clinical patterns. Recently, it has been suggested that almost all of the histologic features described under the name of polymorphic reticulosis(PR), lethal midline granuloma, and midline malignant reticulosis can be included in those generally described for malignant lymphomas of peripheral T cell origin(PTCL). There have been few studies of pathogenesis or tissue damage mechanism in PR patients. The need for a precise mechanism for tissue damage has important therapeutic implications. Using immunohistochemical methods with polyclonal anti IL-6 antibody, the authors describe 5 cases of PR with clinically and pathologically typical PR demonstrating a high expression of IL-6. According to classification, 2 cases of grade 1 PR showed the highest expressions, and 2 cases of grade 2 PR with atypical lymphoid cells showed moderate activity, but one case progressed into frank lymphoma(grade 3) and lost IL-6 expression. This strongly implies that some cases of PR have a different mechanism of tissue damage from frank PTCL, despite the one disease spectrum. Further studies on more cases may help clarify the pathogenesis.     

Two cases of common bile duct stone after liver transplantation

Biliary complications after orthotopic liver transplants are a continuing cause of morbidity and mortality. Biliary stones and sludge are less well known complications of hepatic transplantation, although they have long been recognized. Recently we experienced two cases of biliary stones developed after liver transplantation. One 32-year-old male, who frequently admitted due to recurrent cholangitis, was treated with percutaneous transhepatic biliary drainage and choledochojejunostomy with cholecystectomy. The other 58-year-old male, who had stones in commone bile duct, was treated by endoscopic manipulation. They are in good condition without recurrent bile duct stones or its accompanying complications. Although stones and sludge are relatively infrequent after liver transplantation, surgical or interventional radiologic treatments are usually performed for treatment.     

Surgonomics: the cost dynamics of craniotomy

Prospective payment systems using the diagnostic related group (DRG) mechanism are being phased in for Medicare inpatient hospital care. The purpose of this study was to examine a common neurosurgical procedure (001), craniotomy without trauma, and characterize the cost dynamics of this DRG. All patients (n = 50) treated in this DRG at the Long Island Jewish Medical Center during 1983 had their financial charges exclusive of physician fees examined. The findings were: (a) each hospital service category had wide charge variances around the mean; (b) emergency (ER) admissions were 200% more expensive than nonemergency (non-ER) admissions; (c) ER admissions seemed to have no greater severity of illness than non-ER admissions, but had a significantly different referral pattern (i.e., admission from the ER to a nonneurosurgical service with a subsequent neurosurgical referral); (d) this DRG when grouped into clinical "subproducts" (i.e., craniotomy for tumor, hematoma, hydrocephalus, aneurysm, benign cyst, and other) showed marked charge differences; and (e) the most expensive 25% of patients had five times higher charges than the least expensive 25% for both ER and non-ER admissions. This type of financial analysis may give surgeons a methodology with which to address the problems of cost containment in a more serious manner.     

A prognostic immune predictor,HLA-DRA,plays diverse roles in non-muscle invasive and muscle invasive bladder cancer

BackgroundThere is an increasing demand for prognostic immune biomarkers of cancer. The prognostic significance of immune markers has been shown for various cancers, but biomarkers of bladder cancer (BCa) have not been fully evaluated. To clarify the role of human leukocyte antigen DR alpha chain (HLA-DRA) in BCa development, we examined expression of HLA-DRA mRNA in tissue samples of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC).Materials and MethodsTissues of 96 NMIBC, 43 MIBC and 59 controls comprising noncancerous BCa surrounding tissues were used to examine the expression of HLA-DRA gene by real-time polymerase chain reaction. The expression of up-stream genes regulating HLA-DRA were also measured to explain the role of HLA-DRA in BCa.ResultsPatients with high grade NMIBC showed higher expression of HLA-DRA than those with low grade NMIBC (P < 0.05). In addition, NMIBC patients who progressed to MIBC showed high expression of HLA-DRA mRNA. Kaplan-Meier analysis showed that NMIBC patients with low expression of HLA-DRA had better progression-free survival than those with high expression (P = 0.004). Moreover, the expression of genes regulating HLA-DRA varied in NMIBC and MIBC, indicating a different immunoregulation effect of HLA-DRA in both cancers.ConclusionsHigh expression of HLA-DRA in NMIBC patients has implications for patient stratification strategies, as well as for BCa tumor immunology.     

Collision tumors of the ovary associated with teratoma: clues to the correct preoperative diagnosis

PURPOSE: Collision tumors represent a coexistence of two adjacent but histologically distinct tumors without histologic admixture in an organ. The purpose of this study was to describe the imaging findings of collision tumors of the ovary associated with teratoma and to look for clues that might lead to the correct preoperative diagnosis. METHOD: Seven pathologically proven cases of collision tumor of the ovary associated with teratoma were retrospectively reviewed. Ovarian teratomas were coexistent with mucinous cystadenoma (n = 4), borderline mucinous tumor (n = 1), mucinous cystadenocarcinoma (n = 1), and dysgerminoma (n = 1). US (n = 5), CT (n = 3), and/or MRI (n = 4) findings were evaluated. RESULTS: In addition to the typical findings of teratoma, the mass contained a multiloculated cystic portion filled with nonfatty fluid, suggesting the coexistent epithelial tumor in five cases. In one case, the mass contained a large solid component, suggesting the possibility of collision tumor. In the remaining one case, coexistent small mucinous cystadenoma could not be identified. CONCLUSION: Preoperative imaging for ovarian teratoma revealed a collision tumor in six of seven cases. The possibility of a collision tumor should be considered when an ovarian teratoma has imaging findings that cannot be explained solely by an ovarian teratoma.     

Effect of the transligamentous extension of lumbar disc herniations on their regression and the clinical outcome of sciatica

STUDY DESIGN: Magnetic resonance imaging of symptomatic herniated lumbar discs was investigated longitudinally and prospectively for the presence of tear in the posterior longitudinal ligament (PLL). OBJECTIVES: To clarify the effect of transligamentous extension through the PLL of herniated disc on its regression and to determine the factors contributing to a successful clinical outcome. SUMMARY OF BACKGROUND DATA: Greater regression of the herniated fragment has been noted with larger initial disc herniations. The exposure of herniated disc materials to the epidural vascular supply through the ruptured PLL has been suspected to play a part in the mechanism of disappearance of the herniated nucleus pulposus. However, it had not been shown clinically. METHODS: Clinical outcomes and magnetic resonance images of 36 patients with symptomatic lumbar disc herniations, treated conservatively, were analyzed. Patients were divided into three groups: subligamentous, transligamentous, and sequestered herniations. The size of the herniated disc was measured by herniation ratio, which is defined as the ratio of the area of herniated disc to that of the thecal sac on the axial view. Factors associated with the natural regression of herniated disc and the successful clinical outcome were explored. RESULTS: Of the 36 herniated discs, 25 decreased in size. Ten (56%) of 18 subligamentous herniations, 11 (79%) of 14 transligamentous herniations, and all 4 (100%) sequestered herniations were reduced in size. The average decreases in herniation ratio of the subligamentous, transligamentous, and sequestered disc groups were 17%, 48%, and 82% respectively. The decrease in herniation ratio was related to the presence of transligamentous extension but was not related to the initial size of herniation. Successful outcome correlated with a decrease in herniation of more than 20%. CONCLUSION: Transligamentous extension of herniated disc materials through the ruptured PLL is more important to its reduction in size than is the initial size of the herniated disc. Decrease in herniation ratio of more than 20% seems to correspond to successful clinical outcome.     

Expression of placental growth factor gene in lung cancer.

Differences in the gene expression profiles in small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC) may explain their different clinical characteristics. The aims of this study were (1) to identify genes differentially expressed in SCLC and NSCLC using mRNA differential display, and (2) to determine the clinical relevance of such genes in lung cancer. RNA differential display using three SCLC and six non-SCLC cell lines was used to identify a differentially expressed gene. Differential expression of the gene was confirmed in additional lung cancer cell lines using RT-PCR. Immunohistochemical staining for the gene product was performed on paraffin-embedded tissue from lung cancer patients. We examined the relationship between the expression of the gene and clinical parameters, including disease stage, response to treatment and survival time. The placental growth factor (PGF) gene was identified as preferentially expressed in SCLC compared with NSCLC cell lines using mRNA differential display. Further analysis of 45 lung cancer cell lines using RT-PCR showed that the placental growth factor (PGF) gene was expressed in nine of 13 SCLC cell lines (69%) and five of 32 NSCLC cell lines (15.6%) (p < 0.001, Fisher's exact test). Immunohistochemistry using anti-PGF antibody on the paraffin blocks from lung cancer patients showed that PGF expression was significantly higher in SCLC than NSCLC tissue sections (32 vs. 5.6%, p = 0.041, Fisher's exact test). Expression of PGF protein did not correlate with disease stage, response to treatment or survival time in SCLC patients. The present study suggests there is higher expression of PGF in SCLC compared to NSCLC. It may be that higher expression of the angiogenic factor PGF contributes to differences between the progression of SCLC and NSCLC, especially in regard to the nature of SCLC metastasis.