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.     

Effect of thromboxane A2 synthetase inhibitor on immediate-type hypersensitivity reactions

The effect of the thromboxane (TX) A2 synthetase inhibitor, OKY-046, on human leukocyte histamine release and bronchial hypersensitivity in asthmatic subjects was evaluated. It was found that OKY-046 inhibited IgE- and Ca2+ ionophore A23187-mediated leukocyte histamine release in a dose-dependent fashion (IC50: 1.0 and 3.0 X 10(-3) M, respectively) and that OKY-046 could diminish bronchial hypersensitivity, determined by leukotriene D4 inhalation, following a 2-week oral medication. These data suggest that the TXA2 synthetase inhibitor can produce favorable effects upon the course of immediate-type hypersensitivity reactions.     

A basic study of determination matrix metalloproteinase-3 and carbohydrate in rheumatoid factor in serum for diagnosis of rheumatoid arthritis

The examination of rheumatoid factor (RF), one of the diagnostic marker of rheumatoid arthritis (RA), showed negative about 25% of patients with RA. We analyzed a matrix metalloproteinase-3 (MMP-3) and a carbohydrate in rheumatoid factor (CA.RF) for diagnosis of RA: the former is used the kit "Panaclear MMP-3[Plate]" and the latter is used the kit "Picolumi CA.RF". The basic study of these reagents showed satisfactory results. In 73.3% of seronegative RA showed positive on both MMP-3 and CA.RF levels in serum, respectively. We found that these examinations might be useful for diagnosis of RA, especially during seronegative RA.     

Histological study on healing of cryocautery-induced rat gastric ulcer treated with T-593]

The effect of T-593, a novel anti-ulcer agent, on the healing of cryocautery-induced rat gastric ulcer was investigated histologically in comparison with that of famotidine. Seven days after ulceration, T-593 (30 mg/kg) or famotidine (30 mg/kg) was orally administered twice daily for 8 weeks. Two, 4 and 8 weeks after the start of administration, the ulcer size was measured by a stereoscopic microscope, and the gastric mucosa was observed histologically. The thickness of the regenerated mucosa, the density and the arrangement of gastric glands, the degree of inflammatory-cell infiltration in the submucosal tissue and the number of microvessels in the submucosal tissue were quantified. In macroscopical evaluation, T-593 and famotidine significantly accelerated ulcer healing, and the time courses of the ulcer index were similar in both cases. In histological evaluation of healed ulcers, T-593 normalized the thickness of regenerated mucosa and reduced the degree of inflammatory-cell infiltration and the number of microvessels in the submucosal tissue, while famotidine had no effect. In conclusion, T-593 possesses accelerating effects not only on the restoration of regenerated mucosa but also on the maturation of submucosal tissue. Therefore, T-593 improves the quality of ulcer healing.     

Effects of small dose of brotizolam on P300

Nine healthy men (mean age, 22.2 years) participated in two experimental sessions cross-overed randomly in a double blind manner; one with a placebo and the other with 0.125 mg of brotizolam (BTZ) administered in the morning. Resting electroencephalogram and event-related potential under oddball paradigm was recorded before and 1, 2, 4, 6 and 8 h after the administration. Mean 30-msec bin amplitude from 240 msec to 450 msec after the stimulus was compared between placebo and drug sessions in order to observe P300. Brotizolam reduced the amplitude of P300 at 6 h after administration. It was noted that the effects of BTZ were most marked at Fz.     

Teratoma of the tongue in neonates: report of a case and review of the literature

A female newborn presented with a huge mass protruding from the mouth. She had no respiratory distress but had difficulty swallowing. The mass originated from the tongue and was completely extirpated on the day of birth. The histologic diagnosis was mature teratoma. Three days later, another mass measuring 1 cm in diameter was found attached to the upper pharyngeal wall and was also completely extirpated 20 days after birth. The histologic diagnosis was also mature teratoma. The infant had a complete cleft palate, but no other malformation was found. Two years after surgery there is no sign of recurrence. Accepted: 22 August 1997     

Substituted 3-phenylsulfonylquinazoline-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase

A series of 3-phenylsulfonylquinazoline-2,4-dione derivatives have been synthesized and evaluated for their ability to inhibit human heart chymase. The structure-activity relationship studies on these compounds gave the following results. The phenyl moiety of quinazoline participates in a hydrophobic interaction where an optimum size is required. In this moiety, 7-chloroquinazoline is the best moiety for inhibiting chymase, chymotrypsin and cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrophobic electron-withdrawing groups at the 4-position potentiated the activity. Anthranil moiety also enhanced the activity. Pyridylmethyl and N-pyridylacetamide at the 1-position gave an IC50 in the order of 10(-8)M. Molecular modeling studies on the interaction of 7-chloro-3-(4-chlorophenylsulfonyl) quinazoline-2,4(1H, 3H)-dione (4) with the active site of human heart chymase suggested that the phenyl moiety of quinazoline interacts with the hydrophobic P1 pocket, the 3-phenylsulfonyl moiety resides in the S1'-S2' subsites, the moiety at the 1-position locates in the S2-S3 subsites and the 4-carbonyl and 3-sulfonyl group interact with the oxyanion hole and the His57 side-chain of chymase, respectively.     

Suppressive Effects of the Site 1 Protease (S1P) Inhibitor,PF-429242, on Dengue Virus Propagation

Dengue virus (DENV) infection causes one of the most widespread mosquito-borne diseases in the world. Despite the great need, effective vaccines and practical antiviral therapies are still under development. Intracellular lipid levels are regulated by sterol regulatory elements-binding proteins (SREBPs), which are activated by serine protease, site 1 protease (S1P). Small compound PF-429242 is known as a S1P inhibitor and the antivirus effects have been reported in some viruses. In this study, we examined the anti-DENV effects of PF-429242 using all four serotypes of DENV by several primate-derived cell lines. Moreover, emergence of drug-resistant DENV mutants was assessed by sequential passages with the drug. DENV dependency on intracellular lipids during their infection was also evaluated by adding extracellular lipids. The addition of PF-429242 showed suppression of viral propagation in all DENV serotypes. We showed that drug-resistant DENV mutants are unlikely to emerge after five times sequential passages through treatment with PF-429242. Although the levels of intracellular cholesterol and lipid droplets were reduced by PF-429242, viral propagations were not recovered by addition of exogenous cholesterol or fatty acids, indicating that the reduction of LD and cholesterol caused by PF-429242 treatment is not related to its mechanism of action against DENV propagation. Our results suggest that PF-429242 is a promising candidate for an anti-DENV agent.