Potential immunosuppressive and antiinflammatory activities of Malaysian medicinal plants characterized by reduced cell surface expression of cell adhesion molecules.

In the search for agents effective against immune-mediated disorders and inflammation, we have screened Malaysian medicinal plants for the ability to inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of murine endothelial cells (F-2), and mouse myeloid leukaemia cells (M1), respectively. Of 41 kinds (29 species, 24 genera, 16 families) of Malaysian plants tested, 10 and 19 plant samples significantly downregulated the expression of ICAM-1 and VCAM-1, respectively. Bioassay-directed fractionation of an extract prepared from the bark of Goniothalamus andersonii showed that its ingredients, goniothalamin (1) and goniodiol (2) inhibited the cell surface expression of both ICAM-1 and VCAM-1. The present results suggest that Malaysian medicinal plants may be abundant natural resources for immunosuppressive and antiinflammatory substances.

Synthesis and antitumor activities of novel 5-deazaflavin-sialic acid conjugate molecules.

6-Nitro-5-deazaflavin derivatives bearing O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha- and beta-D-galacto-non-2-ulopyranosylonate)alkyl group (sialosylalkyl group) at N(3) or N(10) and 8-amino-5-deazaflavin substituted with the sialosylalkyl group at the amino group were synthesized and their physicochemical properties as well as antitumor effects on KB and L1210 cells have been investigated. The configurations of the glycosides were determined by 1H NMR and rate of hydrolysis of the glycosidic bond. It has been found that these conjugate molecules show significant antitumor activities. Combination of an 8-amino-5-deazaflavin with the sialosylalkyl group have been found to give rise to significant increase in antitumor activities of the compound. Antitumor effects of 6-nitro-5-deazaflavin-sialic acid conjugate molecules were similar or rather weak in comparison with those of the 6-nitro-5-deazaflavin derivatives without sialosylalkyl group.

Synthesis and evaluation of nitro 5-deazaflavin-pyrrolecarboxamide(s) hybrid molecules as novel DNA targeted bioreductive antitumor agents.

A series of 6-nitro-5-deazaflavins bearing at N(3) or N(10) position the pyrrolecarboxamide(s) group as DNA minor groove binder has been synthesized. These hybrid molecules show similar redox properties to those of 6-nitro-5-deazaflavins with no pyrrolecarboxamide(s) group, suggesting that they generate stable one- and two-electron reduction product(s). Electrolytic reductions of the hybrid molecules were carried out at a controlled potential under anaerobic conditions in the presence of plasmid pBR322 DNA. Significant conversions of the supercoiled circular pBR322 DNA (form I) to the open circular DNA (form II) have been found by treatment with the reductively activated 6-nitro-5-deazaflavin derivatives. Their DNA damaging effects have been found to be enhanced as the number of pyrrolecarboxamide group as the DNA binder increases. Antitumor activities of the hybrid molecules towards KB and L1210 cells were evaluated in vitro. It has been found that the antitumor effects of the compounds on KB cells slightly change and those on L1210 cells decrease as the number of the pyrrolecarboxamide group increases. These results reveal that the combination of 6-nitro-5-deazaflavin molecule with the pyrrolecarboxamide(s) group increase the DNA binding properties of the compounds, giving rise to promoted DNA damaging effects, and also suggest that the combination would affect the capacity of the compounds to act as the substrate for intracellular reductases and/or the cellular uptake of the compounds.

[Comparative study of mRNA expression of E-cadherin and collagenase IV in early and advanced cancers].

During the process of invasion, tumor cells must detach from the primary neoplasm and degrade host stroma. E-cadherin is responsible for the cell-cell adhesion and collagenase IV is the one of the matrix metalloproteinases. We determined whether the levels of mRNA for E-cadherin and collagenase IV were differently expressed within 12 cases of early and 13 cases of advanced gastric cancers using a rapid calorimetric in situ hybridization assay for mRNA. In 6 of 12 early cancers, we found a decreased expression of E-cadherin mRNA in the invasion edge compared to the main tumor. In advanced gastric cancers, 3 out of 13 cancers also exhibited this finding. Higher expression of the collagenase IV at the invasion edge of the tumor compared to the main tumor was observed in half of the early and advanced gastric cancer cases. Inverse expression levels of E-cadherin and collagenase IV mRNA were observed in 6 of 12 early cancers. However, only one of 13 advanced cancer cases expressed the same finding.

Weak expression of blood type B antigen in kidney tissue and successful B-incompatible kidney transplantation without special treatments.

Much attention has been paid to only natural antibody titer of the recipients in ABO-incompatible kidney transplantation. In this study, we looked at the distribution of blood type antigens in the kidney tissue. Thirty-seven biopsy specimens from patients with nephritis or transplanted kidneys were recruited. Fifteen were type A, 14 were type B, and 8 were type AB. Kidney tissues were stained with anti-A or anti-B antibody using immunohistological staining. The stained dots in each section were regarded as the area and were measured by image analyzer. B antigen was expressed very weakly both in the glomeruli and in interstitium as compared with A antigen. In type AB, B antigen was less expressed than A antigen. Based on these results, we performed B-incompatible kidney transplantation. No rejection was seen without preoperative depletion of natural antibody and splenectomy. These results may suggest that type B-incompatible kidney transplantation might possibly be performed without preoperative depletion of natural antibodies.

Fungal metabolites. XIX. Structural elucidation of channel-forming peptides, trichorovins-I-XIV, from the fungus Trichoderma viride.

Trichorovins (TV)-I-XIV are new antibiotic peptides obtained from conidia of the fungus Trichoderma viride. The peptide mixture of TVs was repeatedly fractionated by preparative HPLC until individual TVs showed a single peak on their analytical HPLC chromatograms. Nevertheless, FAB-MS or NMR indicated that each of TVs-I-XIV was composed of at least two components. We attempted to elucidate their structures within the fractions by electrospray ionization (ESI)-MS, FAB-MS, FAB-MS/MS and NMR. TVs generally have molecular weights of approximately 1100-1200 Da, and are characterized by an acetylated N-terminus, the presence of an aminoalcohol, e.g. leucinol, isoleucinol or valinol, at the C-terminus, and eleven residues including three alpha-aminoisobutyric acids in the molecule. Thus, it was determined that TVs belong to the class of peptaibols.

The surgical treatment of aortic dissection in a patient with Turner's syndrome: report of a case.

We report herein the successful surgical management of a 42-year-old patient with Turner's syndrome (TS) complicated by Stanford type B aortic dissection. The patient had a single entry in the proximal descending aorta with dissection extending from the entry point to the abdominal aorto-left iliac bifurcation. A patch plasty using felt reinforcement was performed through a left 4th intercostal space thoracotomy. Her postoperative course was uneventful and she has been well during the 3 years since her operation. There have been only nine reports of patients with TS complicated by aortic dissection for whom operations were performed; however, the details of surgical treatment have not been well documented. This paper reports the course of aortic dissection and the surgical methods employed in the treatment of our patient.

[A case of nonbacterial thrombotic endocarditis presenting positive findings by two-dimensional echocardiography].

A 55-year-old woman was admitted to our hospital because of left hemiparesis. Brain CT and cerebral angiography demonstrated cerebral embolism due to occlusion of the sphenoidal part of the right middle cerebral artery. Two-dimensional echocardiography revealed mitral valve vegetation measuring 10 x 7 mm and slight mitral-valve regurgitation. Blood cultures were negative. She developed disseminated intravascular coagulation. Chest roentgenography and abdominal ultrasonography showed multiple liver and lung tumors, but she died before the primary lesion was detected. At autopsy, adenocarcinoma of the gall bladder was found. Friable vegetation was attached to the auricular surface of the mitral valve. Microscopic examination confirmed the diagnosis of nonbacterial thrombotic endocarditis. Although echocardiography is an important tool for diagnosing nonbacterial thrombotic endocarditis, few reports have described echocardiographic detection of nonbacterial thrombotic endocarditis. Because vegetation of nonbacterial thrombotic endocarditis is smaller than that of infective endocarditis (less than 3 mm), it is difficult for echocardiography to detect nonbacterial thrombotic endocarditis. Thus, a negative examination does not exclude the possibility of nonbacterial thrombotic endocarditis. To make an antemortem diagnosis of nonbacterial thrombotic endocarditis, we must perform echocardiography carefully in cases of cerebral infarction with carcinoma and/or DIC.

[A case report of Bentall procedure for annulo-aortic ectasia associated with right coronary artery dissection].

A 30-year-old man who had annuloaortic ectasia associated with aortic insufficiency owing to marked annular dilatation was treated by replacement of the ascending aorta and aortic valve with a composite graft. It was necessary to transpose the origin of the coronary artery because of the development of dissection to right coronary ostia. We have applied the Bentall procedure with aorta coronary bypass between the right coronary artery and the aortic prosthesis with the use of saphenous vein graft. His post operative course is uneventful and engaging full work 18 month after operation. This technique is useful for the case of annuloaortic ectasia associated with difficulty coronary anastomosis such as coronary artery dissection, obstruction or dislocation.