Effect of corosolic acid on postchallenge plasma glucose levels.

Corosolic acid (CRA) is a substance extracted from Lagerstroemia speciosa L. and has been reported to have biological activities in in vitro and experimental animal studies. In this study, 31 subjects were orally administered 10mg CRA or a placebo, on different occasions, in a capsule 5min before the 75-g oral glucose tolerance test (OGTT) in a double-blind and cross-over design. Nineteen subjects had diabetes, seven had impaired glucose tolerance, one had impaired fasting glucose, and four had normal glucose tolerance according to the 1998 WHO criteria. There were no significant differences in plasma glucose levels before and 30min after the administration. CRA treatment subjects showed lower glucose levels from 60min until 120min and reached statistical significance at 90min. In this study, we have shown for the first time that CRA has a lowering effect on postchallenge plasma glucose levels in vivo in humans.

Changes in platelet demand in association with the spread of autologous peripheral blood progenitor cell transplantation.

Changes in platelet demand accompanying widespread application of autologous peripheral blood progenitor cell transplantation (APBPCT) were anticipated. The differences in the transfused volume of platelet concentrate (PC) among 8 patients with malignant lymphoma who were treated with APBPCT and 10 patients with malignant lymphoma who were not treated with APBPCT, although peripheral blood progenitor cell harvests had been performed, were studied. The former was 81 Japanese PC units more than the latter. Considering the supplied volume of PC from Red Cross blood centers and the number of APBPCTs in 1996 in Japan, the Japanese demand for PC increases by 0.16% for enforced APBPCT versus 0.36%, which includes the PC demand necessary in all treatment courses. The total increment in PC demand associated with APBPCT is not large enough to threaten the PC supply of Japan even if the number of APBPCTs increases rapidly.

[Vacuolar inclusions with multivesicular structure in leukemic multiple myeloma].

A case of leukemic multiple myeloma with IgG-lambda type, which plasma cells in the peripheral blood and the bone marrow had large vacuolar inclusions is reported. A 67-year-old male was admitted because of bone pain. A diagnosis of leukemic multiple myeloma of IgG-lambda type was established, based on Bence Jones proteinuria (1.5 g/day), marked plasmacytosis in peripheral blood (63%) and bone marrow (90%), serum M-component (IgG-lambda type, 6.0 g/dl) and multiple osteolytic lesions. Most plasma cells in the bone marrow as well as in the blood had vacuolar inclusions in the cytoplasm which were 1-8 microns across and were negative with PAS and myeloperoxidase staining. Acid phosphatase reaction was distributed densely around vacuolar inclusions and sparsely within them in the form of fine granules. Ultrastructurally, most of the vacuolar inclusions were electron-lucent cytoplasmic spaces, encircled in a distinct limiting membrane, in which inner microvesicles were distributed diffusely. A few vacuoles showed fibrillary structures. These findings suggested that the lysosomal system might play a major role in the vacuolation of these plasma cells.

Geographical aspects of bcl-2 gene involvement in Japanese patients with non-Hodgkin's B-cell lymphomas.

Using three separate bcl-2 probes, we examined involvement of the bcl-2 gene in Japanese patients with non-Hodgkin's B-cell lymphomas. Of 52 patients with follicular lymphoma (FL), 24 had rearrangements. In a group of 50 patients with diffuse lymphoma, three of 32 patients with diffuse large cell lymphoma had rearrangements. The frequency of rearrangements in each of these groups, as detected by both major and minor breakpoint cluster region probes, was compatible with that found in other Far Eastern studies. However, the difference in frequency between the groups studied in the Far East and the West was significant, and these two geographically distinct populations also displayed a difference in the breakpoint distribution. In the immunophenotype study of 33 patients with FL, the expression of CD10 antigen correlated with bcl-2 involvement, whereas none of the other B markers emerged as parameters to distinguish between the two lymphoma groups; those with, and without, the rearrangements.

Genomic organization of IgH gene compared with the expression of Bcl-2 gene in t(14;18)-positive lymphoma.

In three lymphoma cell lines carrying t(14;18), named FL-18, FL-218, and FL-318, the genomic organization of IgH gene was compared with the expression of bcl-2 gene; the t(14;18) of the FL-18 cells occurred downstream from the major breakpoint cluster region (mbr) of a bcl-2 gene, and that of the FL-218 and FL-318 cells within the mbr. The FL-318 expressed the normal-sized bcl-2 transcript of 8.5-kb mRNA having the noncoding region 3 to the mbr, which was found in the FL-18, and the FL-218 lacking the intact bcl-2 gene did not. This finding suggests that in t(14;18)-positive lymphoma having the breakpoint within the mbr, transcription of the nontranslocated bcl-2 allele is not necessarily silent. In addition, the FL-218 and FL-318 expressed aberrant bcl-2 transcripts and heterogenous IgH transcripts lacking the VH region, and the bcl-2 transcripts each comigrated with parts of the sterile IgH mRNAs. The FL-318, which did not exhibit switch recombination on either IgH allele, contained abundant amounts of l gamma mRNAs, a prerequisite for the recombination into the C gamma locus. One of the I-mRNA species comigrated with the aberrant bcl-2 transcript. The FL-18 and FL-218 lacking the I gamma mRNAs had completed switch recombination of both IgH alleles. This result raises a possibility that deregulated bcl-2 transcription caused by t(14;18) is capable of playing a role in class switch recombination of IgH gene.

[bcl-2 gene involved in Japanese follicular lymphoma].

Using three chromosome 18-specific DNAs, rearrangements of a bcl-2 gene were detected in 20 (44%) of 45 Japanese patients (pts) with follicular lymphoma (FL) and 3 (8%) of 36 pts with diffuse large cell lymphoma. The 21 pts had t (IgH; bcl-2), and of the remaining two who did not display it, one had chromosome t(14; 18). Compared with the findings in American pts, the lower frequency of t(14; 18)-positive lymphoma could reflect a difference in the incidence of overall nodal B lymphoma between Japan and the United States. 11 of 18 pts with t(14; 18)-positive FL expressed CD10 antigen on the cell surface and all 12 pts with t(14; 18)-negative FL did not, and the difference is statistically significant, indicating that t(14; 18)-positive Japanese FL is the same disease entity as most of American FL. Extra 18q- chromosome found in the advanced grade diseases of t(14; 18)-positive lymphoma results in amplification of the rearranged bcl-2 gene on 18q-, suggesting that the change is closely associated with transformation of FL carrying t(14; 18). It is thus possible of international realization to institute the prognostic factors and the treatment strategy for conquering t(14; 18)-positive lymphoma.

Amplified and rearranged bcl-2 gene in two lymphoma cell lines, FL-218 and FL-318, carrying a 14;18 translocation.

Two human B-cell lines carrying a 14;18 chromosome translocation [t(14;18)(q32;q21)], designated FL-218 and FL-318, were established from effusion cells of two Japanese patients manifesting the transformed histology of follicular lymphoma. The FL-218 and FL-318 cell lines were composed of cells in the hyperdiploid range, which had two and three or four 18q- chromosomes, respectively. These 18q- chromosomes were not distinguishable from an 18q- chromosome derived from t(14;18) since they exhibited the same banding pattern. Southern blot analysis revealed that in both cell lines, breakage of the bcl-2 gene occurred within the major breakpoint cluster region and the truncated gene juxtaposed to an immunoglobulin heavy chain gene locus. The autoradiographic intensity of the retained fragment each on 18q- chromosome was more enhanced than that of the translocated fragment on 14q+ chromosome. These findings suggest that the extra 18q- chromosome found in t(14;18)-positive cancer does not arise from de novo independent t(14;18) but from duplication of a preexisting 18q- chromosome.

Immunohistochemical analysis of peripheral T-cell lymphoma in Japanese patients.

The authors immunohistochemically analyzed the phenotype of 40 cases of peripheral T-cell lymphoma, including 12 adult T-cell leukemia/lymphoma (ATL) cases. Molecular genetic analysis of the T-cell receptor beta-chain and immunoglobulin heavy chain genes were also applied to cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-like lymphoma and so-called Lennert's lymphoma. Twenty non-ATL lymphomas expressed a helper/inducer phenotype, whereas only one extranodal case expressed a suppressor/cytotoxic phenotype. Three cases had a CD4-CD8- phenotype, and two cases a CD4+CD8+phenotype. No specific relationship between morphologic characteristics (LSG classification) and phenotype was found among non-ATL lymphomas. Six of eight AILD-like lymphomas had a helper/inducer phenotype. Monoclonality of neoplastic T-cells was demonstrated in six of the seven cases of AILD-like lymphoma by molecular genetic analysis. Two cases of Lennert's lymphoma also showed a helper/inducer phenotype and rearrangement of the T-cell receptor beta-chain gene. Serologically defined ATL cases had a helper/inducer phenotype except in one case that expressed both CD4 and CD8. None of the ATL cases had the CD7 antigen in this study using WT 1 as a CD7 antibody, which is in contrast with the non-ATL lymphomas in which 13 of 25 cases expressed CD7. CD25, strongly detectable in all ATL cases, was negative or weakly expressed in non-ATL lymphomas. These facts suggest that non-ATL and ATL are in the different biologic state, probably resulting from the integration of human T-cell leukemia virus type I (HTLV-I), although both are derived from helper/inducer T-cells.

Supersensitivity of coronary arteries in variant angina to spasm induced by intracoronary acetylcholine.

Acetylcholine (20 to 100 micrograms) was infused directly into coronary arteries in 10 patients with variant angina (group A), 13 subjects without coronary artery disease (group B) and 8 patients with significant organic coronary artery stenosis (greater than or equal to 50%) but without variant angina (group C) during coronary arteriography, to clarify the action of this agent on coronary arteries. Temporary pacing was performed at a demand heart rate of 40 beats/min while bradyarrhythmia developed. Coronary arteriography after administration of acetylcholine showed coronary vasoconstriction in all 10 patients (100%) of group A. Angina accompanied by electrocardiographic ischemic changes in 9 of 10 (90%, 7 ST-segment elevation and 2 depression) was provoked during this test. In the patients of group B, acetylcholine also induced vasoconstriction in 8 of 22 (36%) coronary arterial systems examined, chest pain in 3 (14%) and ST-segment deviation in none (0%). In the patients of group C, acetylcholine induced vasoconstriction in 3 of 9 (33%), chest pain in 2 (22%) and ST-segment depression in 1 (11%). No definite coronary artery dilation induced by acetylcholine was noted. Coronary vasoconstriction (p less than 0.05), electrocardiographic ischemic findings (p less than 0.01) and chest pain (p less than 0.01) were induced significantly more frequently in group A than in both groups B and group C. No significant difference was found between group B and group C. The coronary arteries in the patients with variant angina seem to be more susceptible to acetylcholine than those of patients without variant angina irrespective of the presence of significant atherosclerosis.