The fifth epidermal growth factor-like region of thrombomodulin exerts cytoprotective function and prevents SOS in a murine model.

The present study found that the fifth epidermal growth factor-like domain of thrombomodulin (TME5) possesses the cytoprotective function in association with an increase in levels of anti-apoptotic myeloid cell leukemia-1 protein in an activated protein C-independent manner in human umbilical vein endothelial cells (HUVECs). Importantly, TME5 counteracted calcineurin inhibitor-induced vascular permeability and successfully prevented monocrotaline-induced sinusoidal obstruction syndrome (SOS) in a murine model. Taken together, TME5 may be useful for preventing or treating lethal complications that develop after hematopoietic stem cell transplantation such as SOS and thrombotic microangiopathy in which endothelial cell damage has a role.

Portal or superior mesenteric vein resection in pancreatoduodenectomy for pancreatic head carcinoma.

BACKGROUND: The aim of this study was to determine the added value of portal or superior mesenteric vein (PV/SMV) resection during pancreatoduodenectomy for pancreatic head carcinoma. METHODS: A multicentre observational study was conducted in patients with pancreatic head carcinoma who underwent pancreatoduodenectomy in seven Japanese hospitals between 2001 and 2012. Clinicopathological factors were compared between patients who did and did not undergo PV/SMV resection. Those with an impact on survival were identified by univariable and multivariable analysis. RESULTS: Of the 937 patients who underwent pancreatoduodenectomy, 435 (46·4 per cent) had PV/SMV resection, whereas the remaining 502 (53·6 per cent) did not. Some 71·5 and 63·9 per cent of patients with and without PV/SMV resection respectively had lymph node-positive disease. Patients who underwent PV/SMV resection had more advanced tumours. Perioperative mortality and morbidity rates did not differ between the two groups. Multivariable analysis revealed that PV/SMV resection was not an independent prognostic factor for overall survival (P = 0·268). Among the 435 patients in whom the PV/SMV was resected, borderline resectable tumours with arterial abutment (P = 0·021) and absence of adjuvant chemotherapy (P < 0·001) were independent predictors of poor survival in multivariable analysis. Patients with resectable or borderline resectable tumours with PV/SMV involvement had a median survival time with additional adjuvant chemotherapy of 43·7 and 29·7 months respectively. Median survival time in patients with borderline resectable tumours with arterial abutment was 18·6 months despite adjuvant chemotherapy. CONCLUSION: Pancreatoduodenectomy with PV/SMV resection and adjuvant chemotherapy in patients with pancreatic head carcinoma may provide good survival without increased mortality and morbidity.

A bis-sesquiterpene and sesquiterpenolides from Inula macrophylla.

Macrophyllidimer C, a novel bis-sesquiterpene, in which the two sesquiterpene units are directly connected by a C-C bond, and eight other sesquiterpenolides were obtained from the bark of Inula macrophylla. Seven of these, macrophyllilactones A-G, are new eudesmanolide- and elemanolide-type sesquiterpenes. Their structures were determined on the basis of spectroscopic evidence and chemical reaction.

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.

Molecular cloning, functional expression and characterization of (E)-beta farnesene synthase from Citrus junos.

We cloned the gene of the acyclic sesquiterpene synthase, (E)-beta-farnesene synthase (CJFS) from Yuzu (Citrus junos, Rutaceae). The function of CJFS was elucidated by the preparation of recombinant protein and subsequent enzyme assay. CJFS consisted of 1867 nucleotides including 1680 bp of coding sequence encoding a protein of 560 amino acids with a molecular weight of 62 kDa. The deduced amino acid sequence possessed characteristic amino acid residues, such as the DDxxD motif, which are highly conserved among terpene synthases. This is the first report of the cloning of a terpene synthase from a Rutaceous plant. A possible reaction mechanism for terpene biosynthesis is also discussed on the basis of sequence comparison of CJFS with known sesquiterpene synthase genes.

Sesquiterpenoids from the fruits of Ferula kuhistanica and antibacterial activity of the constituents of F. kuhistanica.

Ethyl acetate extracts of the air-dried fruits of Ferula kuhistanica afforded three daucane esters: kuhistanicaol H, I and J, together with nine other known compounds. Their structures were established on the basis of spectroscopic evidence. Isolated compounds in this paper and previously reported compounds from the roots and stems of F. kuhistanica were tested for antibacterial activity. Some of them were selectively toxic against Gram-positive bacteria, including methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA).

Phlomisflavosides A and B, new flavonol bisglycosides from Phlomis spinidens.

From the aerial parts of Phlomis spinidens, two new flavonol bisglycosides, phlomisflavosides A (1) and B (2), were isolated together with the known compounds, astragalin, isoquercitrin, lamiridoside, phlomoside A, shanzhiside methyl ester, 8-O-acetylshanzhiside methyl ester, phlorigidoside C, rodioloside (=salidroside), forsythoside B, citroside A and lariciresinol-4'-O-beta-D-glucoside. The structures of the new compounds were elucidated based on spectral and chemical evidence.

Chemical constituents of Prangos tschiniganica; structure elucidation and absolute configuration of coumarin and furanocoumarin derivatives with anti-HIV activity.

The methanol extract of the dried aerial parts of Prangos tschimganica gave three new coumarin derivatives and 30 known coumarin derivatives. Their structures were established on the basis of chemical and spectroscopic evidence. Absolute configuration of the isolated compounds were determined by using a modified Mosher's method. Some of the isolated compounds showed anti-HIV activity.

Farnesyl hydroxybenzoic acid derivatives from Ferula kuhistanica.

Four new farnesyl hydroxybenzoic acid derivatives, kuhistanols E-H (1-4), were isolated from the roots of the Uzbekistan medicinal plant Ferula kuhistanica. The structures of the new compounds were elucidated based on spectroscopic and chemical evidence.

Terpenoids and gamma-pyrone derivatives from Prangos tschimganica.

The methanol extract of the dried aerial parts of Prangos tschimganica afforded seven monoterpenoids and four gamma-pyrone derivatives. Their structures were established on the basis of chemical and spectroscopic evidence.

Traditional medicine in Turkey X. Folk medicine in Central Anatolia.

Traditional medicine used in Central Anatolia; Ankara, Kayseri, Nigde and south-eastern parts of Karaman and Konya provinces have been studied. Two hundred and ninety one folk remedies obtained from 103 plant species belonging to 40 families and 4 animal species are reported with their vernacular names, parts used, methods of preparing remedies and therapeutic usage.

In vitro inhibitory effects of Daphne oleoides ssp. oleoides on inflammatory cytokines and activity-guided isolation of active constituents.

Aerial parts of Daphne oleoides Schreber ssp. oleoides (Thymelaeaceae) are used to treat rheumatoid arthritis and lumbago in Turkish folk medicine. In order to evaluate folkloric utilization, in vitro inhibitory effects of the ethyl acetate extract and fractions obtained from this extract on interleukin 1 (IL-1alpha, IL-1beta) and tumour necrosis factor (TNF-alpha) biosynthesis were studied. Through chemical isolation techniques and activity-guided fractionation process, seventeen compounds were isolated and their structures were elucidated (numbered 1-17). Diterpenoids genkwadaphnin (3) and 1,2-dehydrodaphnetoxin (6) and a coumarin derivative daphnetin (9) showed potent inhibitory activity and were found to be the main active ingredients. Furthermore, gnidilatin (4), gnidilatin-20 palmitate (5), genkwadaphnin-20-palmitate (7) and gnidicin-20-palmitate (8), having diterpenoid structure, and eudesmine (12), wikstromol (13) and matairesinol (14), having lignan structure, were determined to possess moderate inhibitory activity and may have a contributory role in the effect of the remedy.

Molecular cloning, functional expression and characterization of d-limonene synthase from Schizonepeta tenuifolia.

Limonene is one of the most simple cyclic monoterpenes, and two enantiomers, d- and l-limonene occur due to the chiral carbon at 4-position. Cyclization of GPP into limonene is catalyzed by the limonene synthase, and some l-limonene synthase cDNAs have already been cloned from several species of plants, mainly from Labiatae family. However, the d-limonene synthase gene has not yet been obtained, therefore, no information is available on the molecular mechanism of stereochemical regulation in limonene formation. To resolve this, we cloned the d-limonene synthase gene (dLMS) from Schizonepeta tenuifolia (Labiatae) by a reverse genetic approach, and we found that both d- and l-limonene synthase share similar features such as a transit peptide, an arginine rich domain, and a metal cation binding site in their structures. Here, we report on the cloning of dLMS, and the putative stereochemical regulation mechanism is discussed based on the comparison of the deduced amino acid sequence of dLMS with those of known l-limonene synthases.

Panic disorder cases in Japanese-Brazilians in Japan: their ethnic and cultural confusion.

The comparatively high salaries made in Japan are attractive to many Japanese-Brazilians. The number of individuals from this ethnic group being treated in Japanese mental hospitals has increased. We hypothesized that Japanese-Brazilian patients with panic disorders adjusted better to Japanese society and culture than those with other mental disorders. The subjects in the present study are 40 Japanese-Brazilian patients undergoing treatment at the Department of Psychiatry at Jichi Medical School, Japan, from May 1990 to September 1998. Patients were divided into a panic disorder group, a schizophrenic group, a mood disorder group and a neurosis group. Demographic data (Japanese language ability, duration of residence in Japan etc.) were collected. A comparison was made among the four groups. Patients in the panic disorder group showed a significant tendency to be fluent speakers of Japanese. Patients in the panic disorder group also had been in Japan for a significantly longer period of time than those in the other three groups. Japanese ability and length of residence in Japan rule out exacerbating factors due to a foreign living environment. Panic disorder patients usually have resolved the problems inherent in living and working in a foreign country. In general, Japanese-Brazilians are more comfortable both financially and socially in Japan than other foreign laborers because of their cultural and family background. The emotional conflict experienced by such patients may result from concern over whether to live in Brazil or Japan in the future. Their ethnic and cultural identity may be confused, fluctuating between identifying with Brazil and with Japan, and this may cause vague feelings of anxiety.

Influence of natural and synthetic compounds on cell surface expression of cell adhesion molecules, ICAM-1 and VCAM-1.

Various natural and synthetic compounds including alkaloids, terpenoids and phenolics were tested for inhibition of the cell surface expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), both of which are crucial in the regulation of immune response and inflammation. Of 40 compounds tested, two compounds significantly downregulated the expression of VCAM-1 on murine endothelial cells (F-2) and ten compounds that of ICAM-1 on mouse myeloid leukemia cells (M1). Sanguinarine chloride (5) and isoliquiritigenin (13) were capable of lowering the levels of both ICAM-1 and VCAM-1. The structure-activity relationships study on chalcone and flavone derivatives related to 13 suggested that the inhibitory activity of the chalcone derivatives is attributable to the 4-hydroxy group as well as the possible coplanarity between the phenyl ring and the adjacent conjugated ketone.

Sesquiterpenes and monoterpenes from the bark of Inula macrophylla.

Eleven new sesquiterpenes (1--11) and two thymol derivatives (12, 13), along with 12 known sesquiterpenes and monoterpenes, were isolated from the bark of Inula macrophylla. Their structures were determined on the basis of spectral evidence (especially by HREIMS and 2D NMR) as well as chemical transformations. The structure of macrophyllic acid A (1) was confirmed by X-ray analysis, and the absolute configuration of 1 was determined on the basis of the appropriate chemical conversions and the application of a modified Mosher's method.

Phenylbutanoids and stilbene derivatives of Rheum maximowiczii.

The methanol extract of the dried roots of Rheum maximowiczii afforded four phenylbutanoid and two stilbene derivatives. Their structures were established on the basis of chemical and spectroscopic studies.

Inhibitory effect of decoction of Perilla frutescens on cultured murine mesangial cell proliferation and quantitative analysis of its active constituents.

The leaves of Perilla frutescens (perilla) are a common herb used in Japan for garnishing raw seafood. Previously, we reported that a decoction of perilla leaves had suppressive effects on the progression of glomerulonephritis in an animal model of spontaneous IgA nephropathy. The objective of the present study was to isolate anti-nephritic constituents in the perilla decoction under the guidance of its in vitro anti-proliferative activity on cultured murine mesangial cells, and to measure the contents of the active constituents in decoctions prepared from various perilla chemotypes, which differ in their composition of essential oils and/or pigments. DNA synthesis of cultured mesangial cells induced by 1% fetal calf serum was significantly inhibited by the perilla decoction (IC50 values, 8.8 microg/ml). Caffeic acid, luteolin 7-O-[beta-glucuronosyl(1-->2)beta-glucuronide], apigenin 7-O-[beta-glucuronosyl(1-->2)beta-glucuronide], scutellarin, and rosmarinic acid were isolated as active constituents. The contents of these phenolic compounds were not significantly different among chemotypes of P. frutescens. Considering the relation between the contents in the perilla decoction and the activities of these compounds, rosmarinic acid represents the in vitro anti-proliferative effect of perilla decoction.

Suppressive effects of Perilla frutescens on mesangioproliferative glomerulonephritis in rats.

Leaves of Perilla frutescens var. crispa DECNE. (perilla, Labiatae) are used as a garnishing vegetable in East Asian countries as well as an herbal medicine prescribed in Kampo medicines such as Saiboku-to. A previous in vitro study revealed that a decoction of perilla leaves inhibits the proliferation of murine-cultured mesangial cells. In the present study, we evaluated the in vivo anti-proliferative effects of a perilla decoction using rat mesangio-proliferative glomerulonephritis induced by an intravenous injection of rabbit anti-rat thymocyte serum (ATS). Leaves of perilla were boiled, and the decoction was orally administered to the rats as drinking water at doses of 100 and 500 mg/kg/d from the day of ATS-injection (day 0) to day 8, when rats were sacrificed. In the histological evaluation, the total number of glomerular cells, proliferating cell nuclear antigen (PCNA) positive cells, and macrophage/monocyte antigen-positive cells in the glomerulus, was significantly decreased in perilla-treated rats. A significantly lower level of proliferation was induced by the serum of the perilla-treated rats than by that of the controls. These results suggest that the perilla decoction suppresses the proliferation of mesangial cells in vivo by an inhibition of the glomerular infiltration of macrophage/monocytes and of the production of circulating growth factors.

Clinicopathologic evaluation of hepatocellular carcinoma with bile duct thrombi.

BACKGROUND: The aim of this study was to evaluate the clinicopathologic characteristics of patients with hepatocellular carcinoma (HCC) and bile duct thrombi (BDT). PATIENTS: Seventeen patients with HCC and BDT among 671 patients with HCC who underwent hepatic resection were enrolled in this study. RESULTS: There were no significant differences in the survival rates between patients with and those without BDT, although the rate of stage IV or portal vein invasion was significantly higher in patients with HCC and BDT than in those with HCC but without BDT. In 9 of 17 patients with BDT, preoperative jaundice was observed. Five of the 17 patients underwent a bile duct resection combined with hepatic resection, and 12 patients underwent hepatic resection with removal of the BDT without bile duct resection. None of the patients had histopathologic evidence of direct tumor invasion into the bile duct wall or of any tumor recurrence related to the BDT. There were no significant differences in the survival rates between patients who underwent bile duct resection and those who did not. CONCLUSION: Hepatic resection and the removal of BDT without bile duct resection were sufficient surgical interventions to treat patients with HCC and BDT.