Postsurgical change in the tracheal bifurcation angle after upper lobectomy: radiographic evaluation

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate postsurgical changes in the tracheal bifurcation angle on chest radiographs after upper lobectomy and to determine whether bronchial repositioning after upper lobectomy mimics that in upper lobe collapse. MATERIALS AND METHODS: The authors selected 81 patients who had undergone upper lobectomy with complete mediastinal and subcarinal lymph node dissection and in whom chest radiographs had been obtained before operation and at four postoperative intervals. The interbronchial angle and the subcarinal angle were measured on the preoperative and postoperative radiographs and compared statistically. RESULTS: The average interbronchial angle and subcarinal angle during any postoperative period were significantly smaller than those before lobectomy (P < .001). These average angles decreased gradually during the postoperative periods. CONCLUSION: The tracheal bifurcation angle was decreased on follow-up chest radiographs in most patients who underwent upper lobectomy with mediastinal lymph node dissection. This finding may be useful for establishing a history of this surgical procedure on the basis of chest radiographs.     

Local delivery of <Superscript>131</Superscript>I-MIBG to treat peritoneal neuroblastoma

Internal radiotherapy involving systemic administration of iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG) in neural crest tumours such as neuroblastoma has shown considerable success. Although peritoneal seeding of neuroblastoma occurs less often than metastases to organs such as the liver, no effective treatments exist in this clinical setting. Previous reports have demonstrated the effectiveness of peritoneal application of chemotherapeutic drugs or radiolabelled monoclonal antibodies in several kinds of carcinomas. Local delivery of ¹³¹I-MIBG should produce more favourable dosimetry in comparison with its systemic administration in the treatment of peritoneal neuroblastoma. In the current investigation, a peritoneal model of neuroblastoma was established in Balb/c nu/nu mice by i.p. injection of SK-N-SH neuroblastoma cells. Two weeks after cell inoculation, comparative biodistribution studies were performed following i.v. or i.p. administration of ¹³¹I-MIBG. Mice were treated with 55.5 MBq of ¹³¹I-MIBG administered either i.v. or i.p. at 2 weeks. Intraperitoneal injection of ¹³¹I-MIBG produced significantly higher tumour accumulation than did i.v. injection (P<0.01). Therapeutic ratios of i.p. injection were 4- to 14-fold higher than those of i.v. injection. Radiotherapy with i.v. administered ¹³¹I-MIBG failed to improve the survival of mice; mean survival of untreated mice and mice treated with i.v. administration of ¹³¹I-MIBG was 59.3±3.9 days and 60.6±2.8 days, respectively. On the other hand, radiotherapy delivered via i.p. administration of ¹³¹I-MIBG prolonged survival of mice to 94.7±17.5 days (P<0.02 vs untreated controls and mice treated with i.v. ¹³¹I-MIBG therapy). Radiation doses absorbed by tumours at 55.5 MBq of ¹³¹I-MIBG were estimated to be 4,140 cGy with i.p. injection and 450 cGy with i.v. injection. These results indicate the benefits of locoregional delivery of ¹³¹I-MIBG in the treatment of peritoneal neuroblastoma.     

Efficient gene transfer to hepatoblastoma cells through asialoglycoprotein receptor and expression under the control of the cyclin A promoter

Specific gene delivery into hepatoma cells by liposomes and specific gene expression under the control of the cyclin A promoter were examined in HepG2 cells, a hepatoblastoma cell line that overexpresses cyclin A. A plasmid carrying the luciferase gene under the cyclin A promoter sequence was condensed with poly-L-lysine and encapsulated into anionic asialofetuin-labeled liposomes (AF-liposomes), which were preferentially taken up by hepatocytes through the action of the asialoglycoprotein receptor (AgpR). AF-liposomes delivered plasmids to the hepatoma cells by receptor-mediated endocytosis through the AgpR, and transgene expression could be achieved under the control of the cyclin A promoter. Furthermore, a fusogenic lipid, DOPE, as a liposomal component was required for the enhancement of transfection efficiency of AF-liposomes.     

Analysis of Sepik populations of Papua New Guinea suggests an increase of CYP2C19 null allele frequencies during the colonization of Melanesia

The cytochrome P450 (CYP) isozyme CYP2C19 metabolizes clinically important drugs, including the anti-malarial proguanil currently used for multi-drug resistant Plasmodium falciparum malaria. CYP2C19 activity varies among geographical regions due to high frequencies of two null alleles (CYP2C19*2/*3) in Asian and especially Pacific populations. Previously, we reported an unprecedentedly high frequency of CYP2C19 poor metabolizers (PM) within populations of Vanuatu, which suggested even higher PM frequencies in Papua New Guinea. We examined CYP2C19 allele frequencies of three malarious populations from inland East Sepik Province, Papua New Guinea to evaluate this prediction and the use of proguanil in malaria treatment programs. These Papua New Guinean populations have PM frequencies intermediate between island South-east Asia and Vanuatu, most likely resulting from genetic drift during the settlement of the Pacific. This study highlights the medical consequences of population origins and the need for a better understanding of the genetic diversity of our global species.     

Angiogenesis inhibitor TNP-470 (AGM-1470) suppresses vascular smooth muscle cell proliferation after balloon injury in rats

BACKGROUND: Although TNP-470, a synthetic analog of fumagillin, may inhibit vascular intimal hyperplasia, the effects of TNP-470 on smooth muscle cell (SMC) proliferation have not been demonstrated in vivo. The aim of this study was to confirm the effect of TNP-470 on vascular SMC proliferation using a rat carotid artery balloon injury model. MATERIALS AND METHODS: Rats were treated with vehicle or with TNP-470 at low dosage (10 mg/kg), medium dosage (20 mg/kg), or high dosage (40 mg/kg). The animals received subcutaneous injections of materials three times a week from the day following balloon injury. All rats were sacrificed at 2 weeks after injury. The ratio of intimal-to-medial cross-sectional areas (I/M ratio) and the PCNA labeling index was calculated for each group. The DNA synthesis of cultured SMCs was also evaluated using [3H]thymidine incorporation assays. Smooth muscle cells were stimulated with basic fibroblast growth factor and TNP-470 (0.01-100 ng/ml) were added. RESULTS: The inhibition of intimal hyperplasia increased in a dose-dependent manner. TNP-470 also decreased PCNA expression in the neointima and inhibited DNA synthesis of cultured SMCs. CONCLUSIONS: TNP-470 may be useful in the prevention of vascular intimal hyperplasia.     

Differential diagnosis of benign peripheral lipoma from well-differentiated liposarcoma on MR imaging: is comparison of margins and internal characteristics useful?

OBJECTIVE: Our objective was to evaluate the reliability of MR imaging in distinguishing between benign lipoma and well-differentiated liposarcoma. MATERIALS AND METHODS: The MR images of 35 pathologically proven benign lipomas in 35 patients and 23 well-differentiated liposarcomas in 17 patients were retrospectively reviewed. T1-, T2-, and fat-suppressed T1-weighted images were obtained after administration of gadopentetate dimeglumine. Margins and internal characteristics revealed on the MR images and the degree of contrast enhancement of septa were evaluated. These MR imaging findings were compared for well-differentiated liposarcomas and benign lipomas. RESULTS: Completely irregular margins were recognized only in benign lipomas with a pathologic diagnosis of infiltrating lipoma. All tumors without a recognizable nonadipose component were benign lipomas (p < 0.05). As for the well-differentiated liposarcomas, thick septa and nodular or patchy nonadipose components were present more frequently in deep and retroperitoneal lesions than in subcutaneous lesions (p < 0.01). No cases showed only thin septa in the deep lesions of well-differentiated liposarcoma, and all cases showed thick septa or nodular or patchy nonadipose components. The septa in well-differentiated liposarcomas enhanced more strongly than did those in benign lipomas. The septa showed no enhancement relative to muscle in 11 of 19 benign lipomas, whereas the septa showed moderate or marked enhancement in all well-differentiated liposarcomas (p < 0.01). CONCLUSION: Careful assessment of margins and internal characteristics on MR imaging can be a useful aid in further distinguishing between biologically different benign lipoma and well-differentiated liposarcoma.     

Cytoplasmic vacuolation in cultured rat astrocytes induced by an organophosphorus agent requires extracellular signal-regulated kinase activation

There are various toxic chemicals that cause cell death. However, in certain cases deleterious agents elicit various cellular responses prior to cell death. To determine the cellular mechanisms by which such cellular responses are induced is important, but sufficient attention has not been paid to this issue to date. In this study, we showed the characteristic effects of an organophosphorus (OP) agent, bis(pinacolyl methyl)phosphonate (BPMP), which we synthesized for the study of OP nerve agents, on cultured rat astrocytes. Morphologically, BPMP induced cytoplasmic vacuolation and stellation in the rat astrocytes. Cytoplasmic vacuolation is a cell pathological change observed, for example, in vacuolar degeneration, and stellation has been reported in astrocytic reactions against various stimuli. By pretreatment with cycloheximide, a protein synthesis inhibitor, stellation was inhibited, although vacuolation was not. Cell staining with a mitochondrion-selective dye indicated that the vacuolation probably occurs in the mitochondria that are swollen and vacuolatred in the center. Interestingly, the extracellular signal-regulated kinase (ERK) cascade inhibitor inhibited vacuolation and, to some extent, stellation. These results suggest that the ERK signaling cascade is important for the induction of mitochondrial vacuolation. We expect that a detailed study of these astrocytic reactions will provide us new perspectives regarding the variation and pathological significance of cell morphological changes, such as vacuolar degeneration, and also the mechanisms underlying various neurological disorders.     

Enlarged Bronchial Arteries in a Fetus with Transposition of the Great Arteries and Intact Ventricular Septum

Enlarged bronchial arteries are associated in some patients with transposition of the great arteries and intact ventricular septum. The etiologyof these enlarged bronchial arteries is not yet known. In this report, we describe a case of TGA/IVS in which enlarged bronchial arteries were demonstrated from the prenatal period. The arteriogram at one year after arterial switch repair demonstrated enlarged bronchial arteries. This prenatal information may be useful for deciding on a strategy for postnatal treatment and counseling the family members.     

Absence of liver tumor promoting effects of annatto extract (norbixin), a natural carotenoid food color,in a medium-term liver carcinogenesis bioassay using male F344 rats

Modifying potential of annatto extract (norbixin) on liver carcinogenesis was investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given annatto extract at dietary levels of 0, 0.03, 0.1 and 0.3%, or phenobarbital sodium at 0.05% as a positive control for 6 weeks. All animals were subjected to partial hepatectomy at week 3, and were killed at week 8. There were no deaths related to annatto extract ingestion, and the treatment had no effects on body weights, or food and water consumption. Statistically significant increases of absolute and relative liver weights were apparent in the 0.1 and 0.3% groups. However, annatto extract did not significantly increase the quantitative values for glutathione S-transferase placental form positive liver cell foci observed after DEN initiation, in clear contrast to the positive control case. The results thus demonstrate that annatto extract at a dietary level of 0.3% (200 mg/kg/day) lacks modifying potential for liver carcinogenesis in our medium-term bioassay system.