The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion.

From January 1986 to December 1988, a prospective trial of transcatheter arterial treatment was carried out for hepatocellular carcinoma (HCC). Two hundred seventy-five patients were included. Okuda's staging system was employed. Patients with Stage I and II HCC were treated by transcatheter arterial embolization (TAE) with a gelatin sponge containing an anti-cancer agent (protocol 1a); a gelatin sponge and iodized oil mixed with an anti-cancer agent (protocol 1b); or iodized oil mixed with an anti-cancer agent (protocol 2). Patients with Stage III HCC were treated with iodized oil with anti-cancer agent (protocol 2). As an exception, patients with an unsuccessful superselective catheterization into the proper hepatic artery by Seldinger technique or obstruction of the main trunk of the portal vein were treated with percutaneous transcatheter arterial infusion into the common hepatic artery regardless of stage (protocol 3). Tumor type and extension, area of tumor involvement, portal vein involvement, method of treatment, and presence of ascites and icterus were found to be the significant factors for an initial response to therapy. Treatment method was the most important factor. Respective survival rates at 1 and 2 years were 70.9% and 55.3% for protocol 1a; 62.3% and 43.8% for protocol 1b; 37.8% and 18.3% for protocol 2; and 16.5% and 0% for protocol 3. Many factors proved to significantly influenced prognosis; however, tumor type had the most important prognostic significance followed by AFP value, ascites, treatment protocol, and area of tumor involvement.     

A case of transient bioprosthetic valve regurgitation and hemolysis devoloping early after surgery using Carpentier-Edwards valve.

The Carpentier-Edwards pericardial bioprosthesis has been markedly improved in the long-term results and valve-related complications including valve dysfunction, compared to the previous generation bioprosthesis. We report a patient in whom transient prosthetic valve regurgitation and hemolysis occurred early after mitral valve replacement using a Carpentier-Edwards pericardial bioprosthesis and were resolved by preservative therapy. The patient was a 77-year-old female diagnosed with severe mitral valve stenosis and insufficiency. She underwent mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis. Opening and closing of the three leaflets looked good on intraoperative transesophageal echocardiography (TEE). The only prosthetic valve regurgitation was evident at the central region where the leaflets form coaptation, and no abnormal findings were seen. Serum lactate dehydrogenase (LDH) was decreased to 405 U/l after surgery. However, LDH again began to increase on the 3rd day after surgery and it increased to 1,830 U/l on the 14th day after surgery. Hemolytic urine was detected on 10th day after surgery. PVL was not detected, but moderate abnormal regurgitation from the outside of the stent pocket was detected on TEE. Revision of valve replacement was considered, but LDH thereafter to 393 U/l on 41st day after surgery. The TEE was repeated, and only a trace of central jet was detected without abnormal regurgitation, unlike the previous examination. The patient did not develop any complications thereafter and was discharged on 47th day after surgery. LDH was nearly normal at the time of discharge.     

Case of acute zonal occult outer retinopathy (AZOOR): a 15 years' mislabeling as retrobulbar optic neuritis]

A 30-year-old woman was admitted to Mie University Hospital for recurrence of sudden visual field defect with photopsia in the right eye. She had experienced the same episodes at the age of 15, 20, 25 and 28 years old. A diagnosis of retrobulbar optic neuritis had been made at each episode, but corticosteroid therapy failed to resolve the symptoms. Neurologic examination on admission was unremarkable except for the visual field defect of the right eye. Brain MRIs with and without gadolinium enhancement were normal. On ophthalmologic examination, visual acuity was normal, but the Mariotte blind spot of the right eye was expanded. Ophthalmoscopic examination, visual evoked potential, flicker electro-oculogram and Hess test were normal. Multifocal electroretinogram (ERG) revealed reduction in the inferior temporal response of the right eye that corresponded to the expansion of the Mariotte blind spot These findings were consistent with conditions of acute zonal occult outer retinopathy (AZOOR). The visual symptoms of AZOOR thus resemble those of retrobulbar optic neuritis and findings of multifocal ERG were useful to differentiate them. AZOOR is a newly established condition, and it is necessary to pay more attention to AZOOR on the differential diagnoses of acute-onset mono ocular visual disturbances.     

Hepatocellular carcinoma with sarcomatous change. Clinicopathologic and immunohistochemical studies of 14 autopsy cases

Among 355 autopsy cases of hepatocellular carcinoma (HCC), 14 cases exhibited sarcomatous appearance (incidence, 3.9%). A clinicopathologic study was performed in these 14 cases, and the immunohistochemical localization of keratin (KRT), vimentin (VMT), albumin (ALB), fibrinogen (FBG) and alpha-fetoprotein (AFP) was also examined using the avidin-biotin complex method. Clinically, the HCCs with sarcomatous appearance were characterized by negative or low serum AFP levels and high incidence of extrahepatic metastasis. Grossly they were of infiltrative, mixed expansive and infiltrative, and pedunculated types. Histologically, the tumor consisted mainly of spindle-shaped cells and partly of multinucleated cells, and showed a sinusoidal growth pattern at the tumor-nontumor boundary. Immunohistochemically, tumor cells in the regions showing sarcomatous appearance were frequently found to be positive to KRT and VMT, whereas the percentage of positivity to ALB, FBG, and AFP were not significantly different from those in ordinary HCC. These results strongly suggest that the lesion showing sarcomatous appearance represents the sarcomatous change of HCC rather than being regarded as the complication of HCC and sarcoma.     

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.