[Survival of 2 years and 7 months with 5'-DFUR treatment in a patient with peritoneal gastric cancer recurrence].

A 79-year-old male patient with peritoneal recurrence of gastric cancer 1 year and 7 months after radical operation was treated by oral administration of 5'-DFUR. After the beginning of oral administration of 5'-DFUR, he survived 2 years and 7 months with a good performance status and without any adverse effects. A very limited number of cases with long survival by the oral administration of 5'-DFUR after peritoneal recurrence of gastric cancer have been reported. Of a total of 653.0 g of 5'-DFUR administrated, 436.8 g (66.9%) were given in a protocol consisting of daily oral 1,600 mg of 5'-DFUR for 7 consecutive days and 7 drug free days. This high-dose (1,053 mg/m2/day) and intermittent method of 5'-DFUR administration might have contributed to the long survival and good performance status of this patient.

Effects of vitamin K2 (menatetrenone) on atherosclerosis and blood coagulation in hypercholesterolemic rabbits.

Gamma-Carboxyglutamic acid (Gla)-containing protein, synthesized in the presence of vitamin K, has been found in atherogenic plaques, but the pharmacological effect of vitamin K on atherosclerosis is unclear. We examined whether vitamin K2 (menatetrenone) could affect the progression of both atherosclerosis and hypercoagulability in hypercholesterolemic rabbits. Vitamin K2 in daily doses of 1, 10 and 100 mg/kg was given with a 0.5% cholesterol diet for 10 weeks to 8 rabbits each. The plasma levels of total-cholesterol in the vitamin K2-treated groups were clearly lower than that of the hypercholesterolemic control group. The excessive dose of vitamin K2, even at the high dose of 100 mg/kg/day for 10 weeks, did not accelerate the progression of atherosclerosis and did not promote the coagulative tendency in the rabbits. In contrast, the vitamin K2 treatment (1 to 10 mg/kg/day) suppressed the progression of atherosclerotic plaques, intima-thickening and pulmonary atherosclerosis, the increase of ester-cholesterol deposition in the aorta, and both the elevation in plasma factor X level and increase in Hepaplastin test value in the rabbits. These results indicate that the pharmacological dose of vitamin K2 prevents both the progression of atherosclerosis and the coagulative tendency by reducing the total-cholesterol, lipid peroxidation and factor X activity in plasma, and the ester-cholesterol deposition in the aorta in hypercholesterolemic rabbits.

[Molecular analysis of a patient with carnitine palmitoyltransferase II deficiency].

Carnitine palmitoyltransferase (CPT), one of the key enzymes of beta-oxidation, translocates long-chain fatty acids from the cytosolic compartment into the mitochondrial matrix to undergo beta-oxidation. Recently, the CPT system has been characterized to consist of two distinct mitochondrial membrane-bound enzymes, CPT I, located on the inner side of the outer mitochondrial membrane, and CPT II, located on the inner mitochondrial membrane. We have investigated a Japanese patient with muscular manifestations who was previously reported as CPT deficiency. Enzymatic analysis of her cultured lymphoblasts revealed that CPT II activity was reduced to 5.8%, indicating that the patient suffered from CPT II deficiency. Molecular analysis identified a missense mutation, a glutamate (174)-to-lysine substitution (E174K), in the CPT II cDNA. The patient was homozygous for the mutation. The presence of the mutation was confirmed by PCR-RFLP with a mismatched primer to generate Mbo II recognition sequence at the mutation site. It has been reported that CPT II deficiency manifests as two different clinical phenotypes: a muscular form and a hepatocardiomuscular form. To our knowledge, this is the first case of CPT II deficiency with muscular symptoms to be characterized by molecular analysis in Japan.

In vitro fertilization and embryo development of Japanese field voles (Microtus montebelli).

Optimal conditions for in vitro fertilization of Japanese field voles (Microtus montebelli) were analysed. The medium used was a modified Krebs-Ringer bicarbonate devised for in vitro fertilization in rats. Ovulated eggs and epididymal spermatozoa were co-incubated in vitro at 37 degrees C under 5% CO2 in air for 6 h, and the eggs were fixed with 2.5% (w/v) glutaraldehyde, stained with 0.25% (v/v) acetolacmoid and examined for evidence of fertilization at the pronuclear stage. Although the fertilization rate with spermatozoa preincubated at 1-2 x 10(8) cells ml-1 for 2 h was very low (1-13%), it was significantly increased (43-51%, P < 0.05) when spermatozoa were preincubated at a lower concentration (1-2 x 10(7) cells ml-1). Furthermore, the fertilization rate was significantly higher with 1 mmol hypotaurine l-1 (74.0%) than without hypotaurine (44.4%, P < 0.05). Fertilization rates of spermatozoa preincubated at 1-2 x 10(7) cells ml-1 for 0.5 or 2 h were similar (69.0% and 73.6%), but a longer preincubation (10 h) resulted in a significantly lower fertilization rate (56.8%, P < 0.01). Vole spermatozoa preincubated for 2 h penetrated the zona pellucida 2 h after insemination, and the sperm heads became decondensed 3 h after insemination. At 6 h after insemination, male and female pronuclei were found in most penetrated eggs. When the eggs were left in the fertilization medium without washing and cultured for 96 h after insemination, they developed to two-cell (82.6%), four-cell (60.9%), eight-cell (23.2%) and morula/blastocyst (8.7%) stages in modified Krebs-Ringer bicarbonate supplemented with 1 mmol hypotaurine l-1.