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.     

Pulmonary tuberculosis in five young infants with nursery exposure: clinical, radiographic and CT findings

Clinical, radiographic (n = 5) and CT findings (n = 4) of five Korean infants ranging in age from 2 to 3 months with confirmed tuberculosis were retrospectively analysed. All of the patients were symptomatic, anergic to tuberculin, and had a positive culture of Myobacterium tuberculosis in gastric aspirates. The probable source of infection was the hospital in which they were born. CT scans demonstrated hilar and mediastinal lymph node enlargement with central low attenuation and peripheral enhancement in all cases. CT may be useful in diagnosis by demonstrating characteristic adenopathy and disseminated disease in young infants. Received: 2 September 1997 Accepted: 23 April 1998     

Differential regulation of ciliary neurotrophic factor and its receptor in the rat hippocampus following transient global ischemia

To investigate a potential role of ciliary neurotrophic factor (CNTF) in transient global ischemia, we have studied the postischemic regulatory changes in the expression of CNTF and its receptor, the ligand-binding alpha-subunit (CNTFRalpha). Immunoblot analysis demonstrated CNTF levels were slightly upregulated already during the first day after ischemia and then increased markedly by more than 10-fold until 2 weeks postischemia. Immunoreactivity for CNTF became detectable 1 day after ischemia and was localized in reactive astrocytes. The intensity of the immunolabeling was maximal in CA1 during the phase of neuronal cell death (days 3-7 postischemia) and in the deafferented inner molecular layer of the dentate gyrus. Upregulation of CNTF expression was less pronounced in CA3 and absent in the stratum lacunosum moleculare and the outer molecular layer of the dentate gyrus and thus did not simply correlate with astroliosis as represented by upregulation of glial fibrillary acidic protein (GFAP). As shown by in situ hybridization, expression of CNTFRalpha mRNA was restricted to neurons of the pyramidal cell and granule cell layers in control animals. Following ischemia, reactive astrocytes, identified by double labeling with antibodies to GFAP, transiently expressed CNTFRalpha mRNA with a maximum around postischemic day 3. This astrocytic response was most pronounced in CA1 and in the hilar part of CA3. These results show that CNTF and its receptor are differentially regulated in activated astrocytes of the postischemic hippocampus, indicating that they are involved in the regulation of astrocytic responses and the neuronal reorganizations occurring after an ischemic insult.     

Percutaneous Placement of Self-expandable Metallic Biliary Stents in Malignant Extrahepatic Strictures: Indications of Transpapillary and Suprapapillary Methods

Objective

To compare the efficacy of suprapapillary and transpapillary methods of transhepatic biliary metallic stent placement in malignant biliary strictures and to specify the indications of each method applied.

Materials and Methods

Stents were placed in 59 patients. Strictures were categorized as type A (within 3 cm of the ampulla, n = 27), type B (over 3 cm from ampulla, n = 7), type C (within 3 cm of the bending portion, n = 9), or type D (over 3 cm above the bending portion, n=16). The stenting method was suprapapillary in 34 cases and transpapillary in 25. The rates of initial and long-term patency and of early recurrence were compared.

Results

Initial patency rates for the suprapapillary and transpapillary methods were 1/7 (14.3%) and 20/20 (100%) respectively for type A (p < 0.0001), 4/5 (80.0%) and 2/2 for type B, 3/7 (42.9%) and 2/2 for type C, and 15/16 (93.8%) and 0/0 for type D. Early recurrence rates were 7/30 (23.3%) using the suprapapillary method and 4/29 (13.8%) using the transpapillary method (p = 0.51). The long-term patency rate did not differ significantly according to either type (p = 0.37) or method (p = 0.62).

Conclusion

For good initial patency, the transpapillary method is recommended for strictures of the distal extrahepatic duct near the ampulla and just above the bending portion. Long-term patency is not influenced by the stenting method employed.     

A co-operative study: clinical characteristics of 334 Korean patients with moyamoya disease treated at neurosurgical institutes (1976-1994). The Korean Society for Cerebrovascular Disease

A co-operative study was conducted to determine the clinical characteristics of patients with moyamoya disease who were diagnosed and treated at neurosurgical institutes in Korea before 1995. Twenty-six hospitals contributed 505 cases and among them, the clinical characteristics of 334 patients with definite moyamoya disease were evaluated. The number of patients began to increase from the late 1980s, and after that approximately 20 patients were treated each year. There were two age peaks: from six to 15 and from 31 to 40 years of age. Haemorrhagic manifestations occurred in approximately 43% of the patients. The major clinical manifestations were haemorrhage in adults (62.4%) and ischaemia in children (61.2%). Overall 54.5% of the patients experienced decreased consciousness levels, mainly due to intracranial haemorrhage or cerebral infarction. In the patients with ischemic manifestations, the adult patients were more likely to have cerebral infarction than the pediatric patients (80% vs. 39%) and the pediatric patients were more likely to have TIA (61% vs. 25%). Thirty eight percent of the patients underwent bypass surgery and 53% of these procedures were performed bilaterally. Treatment policies, including indications for bypass surgery and commonly used drugs, were somewhat different according to the institution. Overall favorable outcome was 73%, and the most significant factor affecting poor outcome was haemorrhagic manifestation. This article describes the characteristics of 334 patients with moyamoya disease, who were diagnosed and treated at neurosurgical institutes in Korea before 1995.     

Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer.

Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. DNA sequence variations in the vascular endothelial growth factor (VEGF) gene may lead to altered VEGF production and/or activity, thereby causing interindividual differences in the susceptibility to lung cancer via their actions on the pathways of tumor angiogenesis. To test this hypothesis, we investigated the potential association between three VEGF polymorphisms (-460T > C, +405C > G, and 936C > T)/haplotypes and the risk of lung cancer in a Korean population. VEGF genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency matched for age and sex. VEGF haplotypes were predicted using Bayesian algorithm in the phase program. Compared with the combined +405 CC and CG genotype, the +405 GG genotype found associated with a significantly decreased risk of small cell carcinoma [SCC; adjusted odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.17-0.78]. The 936 CT genotype and the combined 936 CT and TT genotype were also associated with a significantly decreased risk of SCC compared with the 936 CC genotype (adjusted OR, 0.47; 95% CI, 0.26-0.85 and adjusted OR, 0.44; 95% CI, 0.24-0.80, respectively). Haplotype CGT was associated with a significantly decreased risk of SCC (adjusted OR, 0.39; 95% CI, 0.18-0.87), whereas haplotype TCC conferred a significantly increased risk of SCC (adjusted OR, 1.63; 95% CI, 1.14-2.33). None of the VEGF polymorphisms studied significantly influenced the susceptibility to lung cancer except SCC. However, haplotypes TCT and TGT were significantly associated with the risk of overall lung cancer, respectively (adjusted OR, 0.38; 95% CI, 0.25-0.60 and adjusted OR, 3.94; 95% CI, 2.00-7.76, respectively). These effects of haplotypes TCT and TGT on lung cancer risk were observed in three major histologic types of lung cancer. These results suggest that the VEGF gene may be contribute to an inherited predisposition to lung cancer.     

Abrupt visual loss during anti-vascular endothelial growth factor treatment for type 3 neovascularization

AIM: To investigate the incidence of abrupt visual loss and its associated factors, during anti-vascular endothelial growth factor (VEGF) treatment for type 3 neovascularization. METHODS: This retrospective study included 137 eyes that were newly diagnosed with type 3 neovascularization. All eyes were treated with anti-VEGF therapy. Abrupt visual loss was defined as loss of 5 or more lines in best-corrected visual acuity (BCVA) in comparison to the previous visit. The incidence and timing of abrupt visual loss as well as the factors associated with it, were determined. In addition, the BCVA at the final follow-up was compared between the eyes with and those without abrupt visual loss. RESULTS: The mean follow-up period was 42.4±18.9mo after diagnosis, and abrupt visual loss was noted in 22 eyes (16.1%) at a mean of 19.6±13.9mo. Abrupt visual loss was found to be associated with subretinal hemorrhage in 11 eyes (50.0%), development of or increase in the height of pigment epithelial detachment with fluid in 8 eyes (36.4%), and tears in the retinal pigment epithelium in 3 eyes (13.6%). The logarithm of minimum angle of resolution (logMAR) mean BCVA at the final follow-up was 2.07±0.67 (Snellen equivalents: 20/2349) and 1.00±0.55 (20/200) in eyes with and without abrupt visual loss, respectively. BCVA was significantly worse in the eyes with abrupt visual loss (P<0.001). CONCLUSION: Abrupt visual loss is noted in 16.1% of patients with type 3 neovascularization and is associated with poor visual outcome. Additional studies are needed to determine how abrupt visual loss can be prevented.     

Jejuketomycins A and B,polyketide glycosides with cancer cell migration inhibitory activity from Streptomyces sp. KCB15JA151

Two new polyketide glycosides jejuketomycins A (1) and B (2), were isolated from a culture of Streptomyces sp. KCB15JA151. Their chemical structures including the absolute configurations were determined by detailed analyses of the NMR and HRMS data and ECD calculations and spectral data. Compounds 1 and 2 possess an unusual 6/6/8 tricyclic ring system. Biological evaluation with the wound healing assay and time-lapse cell tracking analysis revealed that compounds 1 and 2 have significant inhibitory activities against cancer cell migration with low cytotoxicity.

Two new polyketide glycosides jejuketomycins A (1) and B (2), were isolated from a culture of Streptomyces sp. KCB15JA151.