Bioconversion studies in cultured cells of Corydalis species.

Structural analysis of the metabolites of dopamine and salsolinol in cultured cells of Corydalis species was carried out using the combination of LC-MS and LC-NMR techniques. Metabolic pathways were clarified without the need to isolate the individual metabolites.

Cassipoureamide-A and -B: new sulfur-containing amides from stem wood of Cassipourea guianensis.

New sulfur-containing amides, cassipoureamide-A (1) and -B (2), have been isolated from the stem wood of Cassipourea guianensis, and their structures were determined to be cis-N-(2-hydroxyethyl)-4-hydroxy-1,2-dithiolane-3-carboxamide and cis-N-(2-hydroxyethyl)-5-hydroxy-1,2,3-trithiane-4-carboxamide, respectively, by MS and NMR studies.

Alternating combination chemotherapy COP (cyclophosphamide, vincristine, prednisone) and MP (melphalan, prednisone) in multiple myeloma: a multicenter phase II study (JCOG8906). Lymphoma Study Group of the Japan Clinical Oncology Group.

BACKGROUND: The main form of cytotoxic treatment for multiple myeloma (MM) is conventional dose chemotherapy at present. METHOD: Between November 1989 and December 1991, a multicenter phase II study of alternating conventional dose combination chemotherapy (CCT) with COP (cyclophosphamide, vincristine, prednisone) and MP (melphalan and prednisone) to evaluate its clinical usefulness for overt MM patients was conducted by the Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG). RESULTS: Eighty-one previously untreated patients were enrolled in the study. For 69 eligible patients, the response rate was 50.7% [95% confidence interval (CI) 38.4-63.0%]. The median survival time was 38.5 (95% CI 32.0-44.4) months. The survival rate at 3 and 5 years was 50.7 and 27.3%, respectively. Grade 4 toxicity by the criteria of the World Health Organization consisted of anemia in eight patients, leucocytopenia in three, cardiac in one and hepatic in two, but there was no treatment-related death. CONCLUSION: The COP-MP regimen for overt MM is thought to be one of the effective CCTs according to the results of the present phase II study.

Minor Flavanones from Erythrina abyssinica

Four new prenylated flavanones, abyssinone-V 4'-methyl ether (1) and abyssinoflavanones IV (2), V (3), and VI (4), have been isolated as minor flavanones from the African medicinal plant, Erythrina abyssinica, together with a known flavanone, sigmoidin D. The structure elucidation of compounds 1-4 by spectroscopic studies is described.

Hypoglycemic activity of some triterpenoid glycosides.

Four triterpenoid glycosides isolated from the rhizomes of Polygala senega var. latifolia, senegins II-IV (1-3) and desmethoxysenegin II (4), were tested for hypoglycemic activity in normal and KK-Ay mice. Compounds 1 and 2 reduced the blood glucose of normal mice 4 h after intraperitoneal administration and also significantly lowered the glucose level of KK-Ay mice under similar conditions. Compounds 3 and 4, as well as senegose A (5), an oligosaccharide ester, were inactive when tested against normal mice.

Cardiotonic activity of the rhizome of Polygonatum sibiricum in rats.

The cardiotonic effect of the rhizome of Polygonatum sibiricum was investigated in the left atria of rats. The methanol extract of the rhizome of Polygonatum sibiricum (OM) (1-7 mg/ml) concentration-dependently increased the developed tension of the left atrium. It also strongly inhibited cAMP phosphodiesterase. The increase cAMP level correlated the increase in left atrial contraction. On the other hand, OM did not inhibit Na+, K+-ATPase. The cardiotonic effect of OM was strongly inhibited by reserpine, a sympatholytic agent. Furthermore, OM-treated left atria inhibited the tension produced by propranolol, a beta adrenocepter antagonist. These findings suggested that the cardiotonic effect is due to stimulating beta adrenoceptors through activation of sympathetic nerves.

Hypoglycemic effect of the rhizomes of Polygala senega in normal and diabetic mice and its main component, the triterpenoid glycoside senegin-II.

The hypoglycemic effect of the rhizomes of Polygala senega L. var. latifolia Torrey et Gray (Polygalaceae) was investigated in normal and KK-Ay mice, one of the model animals of non-insulin dependent diabetes mellitus (NIDDM). The n-butanol extract of senega rhizomes (SN) (5 mg/kg) reduced the blood glucose of normal mice from 191 +/- 3 to 120 +/- 3 mg/dl 4 hours after intraperitoneal administration (P < 0.001), and also showed a significant decrease in the glucose level of KK-Ay mice from 469 +/- 38 to 244 +/- 14 mg/dl under similar conditions (P < 0.001). But streptozotocin-induced diabetic mice did not experience a change in the blood glucose after administration of SN. We propose that the hypoglycemic effect of SN occurs without altering the insulin concentration. Moreover, SN needs the presence of insulin in order to act. In addition, one of the active components of the hypoglycemic effect was identified as a triterpenoid glycoside, senegin-II.

Intraperitoneal administration of Senegae Radix extract and its main component, senegin-II, affects lipid metabolism in normal and hyperlipidemic mice.

The hypolipidemic effect of Senegae Radix, i.e. "Senega," was investigated in normal and hyperlipidemic mice. The n-butanol fraction of the methanol extract of Senegae Radix (SN) (5 mg/kg) significantly reduced the blood triglyceride level of normal mice 7 h after intraperitoneal administration (p < 0.05) and also significantly reduced the blood triglyceride level of cholesterol-fed mice under similar conditions (p < 0.05). SN (5 mg/kg) also reduced the blood triglyceride and cholesterol levels after repeated administration to cholesterol-fed mice. SN also decreased the blood triglyceride level in Triton-induced hyperlipidemia. It is suggested that this fraction contains one or more hypolipidemic components including the main triterpenoid glycoside, senegin-II, which significantly reduces the levels of blood triglycerides in normal mice.

Hypoglycemic activity and structure-activity relationship of iridoidal glycosides.

Four iridoidal glycosides, deacetylasperulosidic acid methyl ester (DE), scandoside methyl ester (SC), geniposide (GE) and gardenoside (GA) isolated from Gardenia jasminoides Ellis grandiflora Makino leaves, were tested hypoglycemic activity in mice. DE lowered the blood glucose level in normal mice. However, SC, GE and GA did not affect the blood glucose level in normal mice, indicating that the absolute configuration of 6 position hydroxy based (OH) should be essential for the biological activity.

Effect of senegin-II on blood glucose in normal and NIDDM mice.

The hypoglycemic effect of senegin-II, the main component of Polygala senega (Polygalaceae), was examined in normal and KK-Ay mice, one of the model animals of non-insulin-dependent diabetes mellitus (NIDDM). Senegin-II (2.5 mg/kg) reduced the level of blood glucose in normal mice from 220 +/- 8 to 131 +/- 5 mg/dl 4 hours after intraperitoneal administration (P < 0.001), and also significantly lowered the blood glucose of KK-Ay mice from 434 +/- 9 to 142 +/- 6 mg/dl under similar conditions (P < 0.001).

Anti-Human T-lymphotropic virus type-I antibodies in atomic-bomb survivors.

Adult T-cell leukemia (ATL), induced by human T- lymphotropic virus type-I (HTLV-I), is endemic in Nagasaki, Japan. To investigate the effects of atomic-bomb radiation on development of this specific type of leukemia, 6182 individuals in the Radiation Effects Research Foundation (RERF) Adult Health Study sample in Hiroshima and Nagasaki were examined for positive rate of HTLV-I antibody. Several lymphocyte parameters were also studied for 70 antibody- positive subjects in Nagasaki. The HTLV-I antibody-positive rate was higher in Nagasaki (6.36%) than in Hiroshima (0.79%) and significantly increased with increasing age, but no association was observed with radiation dose. Whether relationship existed between antibody titer levels and radiation dose among antibody-positive subjects was not The frequency of abnormal lymphocytes tended to be higher in antibody-positive subjects than in antibody-negative subjects, and higher in females than in males regardless of radiation dose. The lymphocyte count was lower in antibody-positive subjects than in antibody-negative subjects and lower in female than in male subjects. No evidence was found to suggest that atomic-bomb radiation plays an important role in HTLV-I infection.

Monoclonal gammopathy in atomic bomb survivors.

An analysis of monoclonal gammopathy in relation to radiation exposure was conducted on atomic bomb survivors examined between October 1979 and September 1981 and between June 1985 and May 1987. There was no overall increase in the relative risk of monoclonal gammopathy and only a suggestive increase in benign monoclonal gammopathy in the second survey which did not achieve statistical significance (P = 0.17). Thirty-one cases were detected among 8796 individuals studied in the first survey, whereas 68 cases were found among 7350 people in the second survey. Among the 31 cases found in the first survey, 9 individuals (29%) died before the second survey: 4 of cancer, 4 of vascular disease, and 1 of infection. Among the 8 individuals with benign monoclonal gammopathy examined in both surveys, 4 developed suppression of residual immunoglobulin(s), suggesting the progression of monoclonal gammopathy. The overall relative risks of monoclonal gammopathy in atomic bomb survivors in the two surveys were not significantly increased with increasing radiation dose. Only benign monoclonal gammopathy in 1985-1987 showed a suggestive increase with radiation exposure. The relative risk of benign monoclonal gammopathy in 1985-1987 was 2.64 in the group exposed to 0.01-0.49 Gy and 2.14 in the > or = 0.50-Gy group (95% confidence intervals = 0.90-8.82 and 0.69-7.31, respectively).

Treatment of disseminated intravascular coagulation and its prodromal stage with gabaxate mesilate (FOY): a multi-center trial.

One hundred and ninety-one patients with disseminated intravascular coagulation syndrome (DIC) or its prodromal stage (preDIC) were treated with only gabaxate mesilate (FOY) (group G) or a combination of gabaxate and unfractionated heparin (group GH), and the efficacy of gabaxate was evaluated in a multicenter study. Following the treatment, the mean DIC score, which was evaluated on the basis of clinical symptoms and hemostatic parameters, decreased significantly to 5.58 +/- 3.48 from 6.75 +/- 3.14 in group G (p < 0.001) and to 6.34 +/- 3.33 from 7.31 +/- 3.00 in group GH (p < 0.05). In patients with overt DIC, the mean score decreased to 6.71 +/- 3.54 from 8.42 +/- 2.84 (p < 0.001). In DIC, the rate of overall efficacy was 46.2% in group G and 35.1% in group GH. In preDIC, it was 41.5% in group G and 27.3% in group GH. No side effects, including severe bleeding, were found in this study. The results indicate that gabaxate mesilate is clinically effective for patients with DIC and preDIC.

A case of beta-thalassemia with a C----T substitution at position 654 of the second intervening sequence of the beta-globin gene.

A 26-year-old Chinese-Malaysian female patient with beta-thalassemia is presented. The main hematological values found in this patient were as follows: 1) normocytic hypochromic anemia (RBC 444 x 10(4)/microliters, Hb 11.8 g/dl) with marked anisopoikilocytosis, 2) erythroid hyperplasia, and 3) increased HbF (HbA 41.4%, HbA2 2.9%, HbF 48.9%). DNA obtained from peripheral leukocytes was analyzed using dot blot hybridization of the polymerase chain reaction (PCR)-amplified DNA with allele-specific oligonucleotide probes. A C----T substitution at position 654 of the second intervening sequence (IVS-2) was detected in her beta-globin clone.

Atomic bomb and leukemia.

Characteristic features of the leukemia among atomic bomb survivors were studied. Dose estimates of atomic bomb radiation were based on T65D, but the new dosimetry system DS86 was used for some analyses. The ratio of a single leukemia type to all leukemias was highest for CML in Hiroshima, and the occurrence of CML was thought to be most characteristic to atomic bomb radiation induced leukemia. The threshold of CML occurrence in Hiroshima is likely to be between 0.5-0.09 Gy. However, the threshold of acute leukemia appears to be nearly 1 Gy. In the distribution of AML subtypes by FAB classification, there was no M3 case in 1 Gy or more group, although several atypical AML cases of survivors were observed. Although aplastic anemia has not increased as a late effect of the atomic bomb radiation exposure, many atypical leukemia or other myeloproliferative diseases who had been diagnosed as aplastic anemia or its related diseases have been experienced among atomic bomb survivors. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral T-cells in several atomic bomb survivors.

[No rearrangement of the breakpoint cluster region in two juvenile chronic myeloid leukemia].

We performed cytogenetic studies and breakpoint cluster region (bcr) rearrangement analysis in two cases of juvenile chronic myeloid leukemia (JCML) which is special type of chronic myeloid leukemia (CML). Case 1 (8-month-old male) and case 2 (3-month-old female) showed clinical and hematologic manifestations similar to CML. Each of case 1 and 2 had normal karyotype and no bcr rearrangement. These findings suggest that JCML is a different heterogeneous disorder from that of adult CML.

A T-cell neoplasia showing clinicopathologic features of malignant histiocytosis with novel chromosomal abnormalities and N-ras mutation.

Malignant histiocytosis (MH) is a distinct disease entity defined clinically and morphologically. However, the neoplastic origin of MH is not well established. The authors report a 26-year-old woman who showed the typical clinicopathologic features of so-called MH. Cytogenetic and molecular genetic examinations were performed in addition to the morphologic and immunologic approach. The expression of CD2 and T-cell receptor gene rearrangements indicated the T-cell origin of this case. CD30, which is positive for anaplastic large cell lymphoma (Ki-1 lymphoma), was not expressed. The cytogenetic study revealed a clonal chromosome abnormality involving 3q25, 6p21, 11p15, and 11q21. An N-ras point mutation within codon 12 (GGT----GCT) was also detected. These finding indicate that MH defined clinically and morphologically is not a tumor of true histiocytic origin and that it should be reclassified on the basis of immunologic, cytogenetic, and molecular genetic data.

Atomic bomb and leukemia.

Characteristic features of leukemia among atomic bomb survivors were studied. The ratio of a single leukemia type to all leukemias was highest for CML in Hiroshima, and the occurrence of CML was thought to be most characteristic for atomic bomb radiation induced leukemia. In the distribution of AML subtypes of FAB classification, there was no M3 cases in 1Gy or more group, although several atypical AML cases of survivors were observed. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral blood of proximal survivors.