Experience of expandable metallic stents for central airway obstruction

The aim of this study was to investigate retrospectively the efficacy of expandable metallic stents (EMSs) for severe respiratory distress in patients with central airway obstruction. Twenty patients with central airway obstructions were treated with an EMS. An intraluminal stricture was present in 15 and an extraluminal stricture in 5 patients. Of the 15 patients with intraluminal stenosis, 11 exhibited symptomatic improvement. All 11 patients had tumor infiltration occupying less than 50% of the endoluminal diameter. The other four patients with intraluminal stenosis had tumor infiltration occupying > 50% of the endoluminal diameter and demonstrated no improvement. All five patients with extraluminal stenosis were improved. EMS is useful for an extraluminal stricture in the central airway and the effect of EMS for intraluminal stenosis is related to the degree of infiltration and of tumor progression itself.      

Cancer detection using a PET tracer, 11C-glycylsarcosine, targeted to H+/peptide transporter.

H+/peptide transporter, PEPT1, is functionally expressed in some human cancer cell lines and might be a candidate molecular target for detection of cancers in vivo using PET. The aim of the present study was to establish a novel tumor-imaging technology using a PET tracer targeted to H+/peptide transporter(s). We also compared the tracer with 18F-FDG, focusing on the specificity of their accumulation between tumor and inflammatory tissues. METHODS: A dipeptide PET tracer, 11C-glycylsarcosine (11C-Gly-Sar), was injected intravenously into athymic mice transplanted with human pancreatic, prostate, and gastric cancer cells. The distribution patterns of 11C-Gly-Sar and 18F-FDG in the tumor-bearing mice, and in mice with inflammatory tissue, were assessed by imaging with a positron planar imaging system (PPIS). Tissue distributions of tracer radioactivity were also measured. The expression levels of PEPT1 and PEPT2 (PEPTs) proteins in tumor xenografts and inflammatory tissue were examined by immunohistochemical analysis. The messenger RNA expression levels of PEPTs in 58 available cancer cell lines were quantified by means of real-time polymerase chain reaction. RESULTS: All 3 tumor xenografts were well visualized with the PPIS after injection of 11C-Gly-Sar. Expression of PEPTs in those xenografts was confirmed by immunohistochemical analysis. Tumor-to-blood concentration ratios of 11C-Gly-Sar increased in a time-dependent manner and were much higher than unity. Most of the radioactivity found in the tumor tissue was recovered as the intact tracer. These results indicated that 11C-Gly-Sar was taken up by the PEPTs in tumor xenografts. It is noteworthy that 11C-Gly-Sar was minimally present in inflammatory tissues that expressed no PEPT1 or PEPT2 protein, whereas 18F-FDG was highly accumulated, with the values of the selectivity index being >25.1 and 0.72 for 11C-Gly-Sar and 18F-FDG, respectively. The mRNAs of PEPT1 and PEPT2 were expressed in 27.6% and 93.1%, respectively, of the cancer cell lines examined in the present study. CONCLUSION: The present study indicates that 11C-Gly-Sar is a promising tumor-imaging agent and is superior to 18F-FDG for distinguishing between tumors and inflammatory tissue. Because PEPTs were ubiquitously expressed in various types of tumor cells examined, 11C-Gly-Sar could be useful for the detection of many types of cancers.     

Effect of cystathionine beta-synthase variant 844ins68bp and methylenetetrahydrofolate reductase A1298C polymorphisms in xenografts on 5-FU efficacy and doubling time

The association of MTHFR and CBS variants with the doubling time and responsiveness to several chemodrugs was analyzed in 26 human cancer xenografts. The tumors homozygous for the absence of insertion (NN) for the CBS 844ins68bp were more chemosensitive than those with insertion (NI) to TS-1 (P=0.0048), suggesting a potential effect of this variant on fluoropyrimidine efficacy. Furthermore, the doubling time of tumors with a variant C allele (AC or CC) in MTHFR-A1298C was significantly longer than that of tumors with a normal allele (AA) (P=0.0008). Twenty-nine cellular proliferation-related genes were associated with MTHFR-A1298C genotyping and with the doubling time.     

Upper thoracic myelopathy caused by vertebral collapse and subluxation in rheumatoid arthritis: report of two cases

We report two cases of rheumatoid arthritis (RA) with upper thoracic myelopathy and a review of the literature. Clinical data of a 47-year-old woman (case 1) and a 54-year-old woman (case 2) are described. Case 1 showed a transverse-type myelopathy at the T2 segment level of the spinal cord and case 2 had the same type of myelopathy at the T4 segment level. Case 1 had anterior vertebral subluxation of C7 due to marked vertebral collapse and Case 2 had subluxation of T2 with vertebral destruction. These two patients had the mutilating type of RA with multilevel spontaneous fusion in the cervical spine. The lesions in the thoracic spine might be caused by the severe destructive inflammation that is characteristic in mutilating disease. The vertebral collapse might lead to subluxation of the upper thoracic vertebra, resulting in spinal cord compression. Upper thoracic subluxation might be caused by vertebral collapse due to RA and the increased motion as a compensation for decreased mobility caused by spontaneous fusion in the cervical spine.     

Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

BACKGROUND: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations. In this study, we analysed mutations in the NCCT gene of seven Japanese patients with GS. METHODS: Peripheral blood mononuclear cells were isolated from patients with GS, their family members and healthy control subjects. A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. In patients with a deletion or splice site mutation, we undertook cDNA sequence analysis. RESULTS: We identified nine mutations. Five of them [c.185C>T (Thr60Met), c.1712C>T (Ala569Val), c.1930C>T (Arg642Cys), c.2552T>A (Leu849His) and c.1932delC] have been reported in Japanese patients, but not in GS patients from other ethnic groups. The remaining four mutations [c.7A>T (Met1Leu), c.1181_1186+20del26, c.1811_1812delAT and IVS16+1G>A] were novel. In cDNA derived from a patient with c.1181_1186+20del26, a deletion of exon 9 and a frameshift at the start of exon 10 were observed. In cDNA derived from patients with IVS16+1G>A, an additional 96 bp insertion between exons 16 and 17 was observed. Six out of seven patients were compound heterozygotes, and the remaining one carried a single heterozygous mutation. CONCLUSIONS: We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations.     

Cyclosporine overcomes cold preservation/reperfusion injury of liver graft: Chemokine release and liver ultrastructure

There is a growing body of evidence that the cytokine, tumor necrosis factor-α (TNF-ga), plays an important role in the development of hepatic ischemia/reperfusion injury. We found that the immunosuppressants, cyclosporine-A (CsA), azathioprine, and FK506, have protective effects on such injury. The purpose of the present study was to elucidate mechanisms involved in these beneficial effects of the immunosuppressant, CsA, on liver injury following cold preservation and transplantation, with special reference to the suppression of TNF-α release. Rat livers were stored in Euro-Collins solution (EC) at 4°C for 6h and orthotopically transplanted. The animals allotted to two groups: group A (untreated controls) and group B (CsA pretreatment of recipients). CsA (10 mg/kg, p.o.) was given for 3 consecutive days preoperatively. CsA pretreatment of the recipients significantly improved the 2-week survival rate (0/6 for group A, 3/6 for group B;P<0.05) and this was associated with a significant decrease in serum TNF-α levels 2h posttransplantation (group A, 69.8±15.7 pg/ml; group B, 22.8±6.8; mean±SEM;n=12 each;P<0.05) and amelioration of sinusoidal endothelial injury, assessed by electron microscopy. Plasma endotoxin levels following reperfusion of the grafts were not altered by the CsA therapy. Morphologically, CsA pretreatment of the recipients did not alter activation of Kupffer cells. CsA pretreatment of the recipient aids in preventing cold preservation/reperfusion injury of the liver graft, possibly by modulating effects of TNF-α.     

Spontaneous mesenteric hemorrhage associated with ehlers-danlos syndrome

The vascular type of Ehlers-Danlos syndrome is a genetic disorder of connective tissue and is frequently associated with catastrophic arterial complications. Its surgical treatment is extremely difficult because of the fragility of vessels. This article describes three patients with vascular type of Ehlers-Danlos syndrome who developed mesenteric hemorrhage due to spontaneous arterial rupture. The clinical and molecular characteristics of the disease are briefly reviewed.