High incidence of nitrosamine-induced tumorigenesis in mice lacking DNA repair methyltransferase

The enzyme O6-methylguanine-DNA methyltransferase repairs alkylation- induced DNA damage, O6-methylguanine and O4-methylthymine, the former being formed more frequently. Previously, by means of gene targeting, we generated mice in which alleles for methyltransferase were disrupted. We now use these mouse lines, which are totally deficient in methyltransferase activity, to examine protective effects of the enzyme against tumor formation. In gene-targeted female mice given an i.p. injection of 5 mg/kg of dimethylnitrosamine, a larger number of liver and lung tumors occurred, as compared with normal female mice treated in the same manner. In male mice given a lower dose of carcinogen, the difference between normal and gene-targeted mice was statistically insignificant although more tumors did form in the gene-targeted mice. Methyltransferase apparently afforded protection from nitrosamine- induced tumorigenesis.      

Inverted T graft: novel technique using composite radial and internal thoracic arteries

BACKGROUND: Multiple arterial revascularization is feasible because of the excellent long-term patency of the arterial grafts compared with venous grafts. We present a new operative technique for multiple arterial revascularization using composite radial and internal thoracic arterial grafts. METHODS: Between January and September 1997, 12 patients had coronary artery bypass grafting with inverted T graft. The indications for inverted T graft were aortic calcification in 4 patients, repeat coronary artery bypass grafting in 1 patient, and total arterial revascularization in 7 young patients. The inverted T graft was constructed by interconnecting the coronary arteries and radial artery with end-to-side and side-to-side anastomoses, and by anastomosing the internal thoracic artery to the side of radial artery. RESULTS: Overall, 38 distal anastomoses (average number per patient, 3.2) were made with an inverted T graft. There were no deaths or perioperative myocardial infarctions. Postoperative angiography disclosed that all of the anastomoses were patent. CONCLUSION: This technique allows multiple arterial revascularizations without technical difficulty. It is useful in patients with aortic calcification, repeat coronary artery bypass grafting patients, and young patients who are candidates for total arterial revascularization.     

A case of advanced breast cancer markedly responding to chemo-endocrine therapy with only slight alopecia

We report a case of good response to chemo-endocrine therapy with slight alopecia. A 55-year-old woman was diagnosed as advanced breast cancer with T4c, N3, M1, Stage IV, who was left cervical node-positive. She received 4 cycles of CTF (cyclophosphamide 100 mg/body/day 1-14, THP 30 mg/body/days 1,8, and 5-FU 750 mg/body/days 1, 8 4 wq) therapy in addition to oral tamoxifen (20 mg/body) administration. After this treatment, the primary tumor was markedly reduced (PR), and only slight alopecia was observed. Generally, 3 cycles of CAF (CEF) therapy induced severe alopecia (grade 3). But this CTF regimen caused grade 1 alopecia. Most women have strong resistance to alopecia. It seems that the quality of life for breast cancer patients was affected by the extent of the alopecia. Therefore, CTF therapy should be considered effective for advanced breast cancer patients while reducing the extent of alopecia.     

Electroencephalographical effects of sarpogrelate hydrochloride versus ticlopidine hydrochloride in elderly patients with peripheral atherosclerosis

The aim was to determine the efficacy of sarpogrelate (a selective 5-hydroxytryptamine-2-serotonergic receptor antagonist) on cerebrovascular function and mean blood pressure (mBP) in elderly patients (> 60 years old). Patients with peripheral circulatory disorders were studied using electroencephalogram (EEG) and mBP measurements before and after 2 years' treatment with either sarpogrelate (n = 31) or ticlopidine (n = 43). Ticlopidine had no significant effect on the whole brain. Sarpogrelate decreased the percentage of slow waves (%slow), but not significantly, and was associated with a smaller change in the percentage of slow waves (delta slow). In the anterior area, neither drug caused significant EEG changes. In the posterior area, sarpogrelate significantly decreased the %slow and increased the %alpha values, and was associated with a significantly higher delta alpha value than ticlopidine. The results suggest that sarpogrelate hydrochloride can suppress serotonin-induced pathological processes in peripheral circulatory disorders and may be recommended as an anti-platelet agent, even in elderly patients with subclinical arteriosclerosis.     

Off‐Pump Coronary Artery Bypass Grafting in Patients with End‐Stage Renal Disease on Hemodialysis

Abstract Background: Coronary artery bypass grafting (CABG) for hemodialysis patients is high risk compared with other patient groups. The aim of this study was to analyze the potential benefits of off‐pump CABG for hemodialysis patients. Methods: From April 1994 through December 2000, 26 hemodialysis patients underwent CABG. The off‐pump group consisted of 15 patients operated on without a pump and the on‐pump group consisted of 11 patients operated on with a pump. Results: There was no difference between the two groups with regard to mean age, mean number of diseased vessels and mean number of anastomoses per patient. No patient died in either group during hospitalization. The postoperative complication rate was low in both groups. The postoperative ventilation time was shorter in the off‐pump group (8.5 vs 26.1 hours, p < 0.001, respectively [off‐pump group vs on‐pump group]). The length of ICU stay was shorter in the off‐pump group (1.7 vs 3.5 days, p # 0.01, respectively [off‐pump group vs on‐pump group]). The medial cost was lower in the off‐pump group ($26,200.80 versus $44,024.10 p # 0.0001 respectively [off‐pump group vs on‐pump group]). Conclusions: Off‐pump CABG provided excellent less‐invasive cardiac surgical results for dialysis patients.     

Antisense in vivo knockdown of synaptotagmin I and synapsin I by HVJ-liposome mediated gene transfer modulates ischemic injury of hippocampus in opposing ways

Neurotransmitter release during and after ischemic event is thought to be involved in excitotoxicity as a pathogenesis for the ischemic brain damage, which is mediated by excessive activation of glutamate receptors and attendant calcium overload. To ascertain the role of transmitter release from nerve terminals in promoting the ischemic neurodegeneration, we delivered antisense oligodeoxynucleotides (ODNs) to synaptotagmin I or synapsin I into the rat brain by using HVJ-liposome gene transfer technique. The antisense ODNs were injected into the lateralventricle in rats 4 days prior to transient forebrain ischemia of 20 min. With a single antisense treatment, long-lasting downregulation of the transmitter release relating protein levels at overall synaptic terminals was achieved. The antisense in vivo knockdown of synaptotagmin I prevented almost completely the ischemic damage of hippocampal CA1 neurons, while the in vivo knockdown of synapsin I markedly promoted the ischemic damage of CA1 pyramidal neurons and extended the injury to relatively resistant CA2/CA3 region. The modulation of ischemic hippocampal damage by the in vivo knockdown of synaptotagmin I or synapsin I suggests that transmitter release from terminals plays an important role in the evolution of ischemic brain damage and therefore the transmitter release strategy by the use of antisense ODNs-HVJ-liposome complex is reliable for neuroprotective therapies.