PubMed Health⌕ Search

Biomedical subjects

M Seto

Publications and source records attributed to M Seto.

At least 235 records · Page 13Linked to original sources
PubMed1989

[The evaluation of split renal function in the experimentally induced transient renal vein obstruction].

The split renal function was measured in order to evaluate the alteration of renal function secondary from transient renal vein obstruction. Three microcuries of I-131 Hippuran and 7 microCi of Tc-99m DTPA were injected into the femoral vein of adult male rats 30 min, 3 hr, 6 hr, 2 days and 1 week after the renal vein obstruction for 30 min. Blood samples were taken from the tail vein 5, 10, 15, 20 and 30 min after injection. Immediately after taking blood sample at 30 min, both kidneys and urinary bladder with ureters were taken. The radioactivities of Tc-99m and I-131 of these samples were measured respectively using a well type scintillation counter at the energy ranges of 140 KeV +/- 25% and 360 KeV +/- 25%. In the obstructed side, the blood clearances of I-131 Hippuran (ERPF) and Tc-99m DTPA (GFR) were decreased at 30 min and 6 hr after the release of left renal vein obstruction. Therefore the filtration fraction was not significantly changed. In conclusion, the single study using either Tc-99m DTPA or I-131 Hippuran may be enough to evaluate the alteration of split renal function in a model of renal vein obstruction, although the combined study using both agents is more preferable.

Animals↗
PubMed1988

Alternative promoters and exons, somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma.

The most common translocation in human lymphoma, the t(14;18)(q32;q21), generates heterogeneous 4.2-7.2 kb Bcl-2-immunoglobulin (Ig) chimeric mRNAs resulting from alternative Bcl-2 5' exons and varied Ig 3' untranslated regions (UT). The normal human Bcl-2 gene has a three exon structure with an untranslated first exon, a facultative 220 bp intron I, but an enormous 370 kb intron II. S1 protection and primer extension analysis defined initiation sites in exon II associated with classic promoter elements and a decanucleotide (ATG-CAAAGCA) homologous with Ig variable region enhancers. Multiple initiation sites were also found in a GC-rich region with Sp1 binding motifs in exon I. Most t(14;18) breakpoints cluster within the 3' UT of Bcl-2 implicating that event in gene deregulation. The Bcl-2 gene introduced into the Ig constant (C gamma) locus of SU-DHL-6 displayed somatic mutation. While Bcl-2--Ig mRNAs demonstrated an unaltered 2.5 h half-life, the Bcl-2--Ig gene revealed an inappropriately high rate of transcription for a mature B-cell. This indicates the translocated Bcl-2 allele has escaped normal control mechanisms.

Amino Acid Sequence↗
PubMed1988

Observation of portal circulation through superior mesenteric vein by enteric coated capsule of thallium-201.

A new method of oral administration of an enteric coated capsule of 201Tl (201Tl-capsule) was developed to evaluate the portal circulation through the superior mesenteric vein (SMV). The 201Tl-capsule was not collapsed in the artificial gastric juice, whereas it melted soon after soaking in the artificial intestinal juice. In a clinical trial of 42 cases, 201Tl was satisfactory released in the duodenum in 36 cases where clear liver images were observed except in 1 patient. Heart to liver ratio (H/L) at 60 or 90 min after duodenal release of 201Tl was 0.32 +/- 0.07 (mean +/- 1 s.d.) in normal controls, 0.34 +/- 0.12 in chronic hepatitis, 0.31 +/- 0.12 in acute hepatitis, 0.45 +/- 0.13 in liver cirrhosis and 0.48 +/- 0.32 in cirrhosis with hepatocellular carcinoma. In 11 patients who had both oral and rectal studies with 201Tl, 7 showed a high H/L ratio of more than 0.8 in the rectal study but only 1 showed a similarly high ratio of 1.07 in the oral study. In the group of varied liver disorders we have studied so far, it was found that most of the SMV blood flowed into the liver and the degree of portal systemic shunting (PSS) from the SMV was much smaller compared to that from the inferior mesenteric vein. The present study with oral administration of the 201Tl-capsule was of value in understanding portal circulation through the SMV, however, this technique seemed of limited usefulness for evaluating overall pathologic PSS.

Capsules↗
PubMed1988

Role of the macrophage in the pathogenesis of experimental autoimmune myasthenia gravis.

To clarify the role of Ia antigen positive macrophages which invade motor end-plates in the induction of the chronic phase, experimental autoimmune myasthenia gravis (EAMG) rats were injected intraperitoneally with silica dust on day 6 after immunization. Silica injection partially inhibited the invasion of motor end-plates with macrophages as compared with a saline injection. The titer of antibodies to the Narke acetylcholine receptor (AChR) in the chronic phase did not differ in either the saline or the silica groups, while the titer of antibodies to rat-AChR (non-crossreactive antibodies) was lower in the silica group than in the saline group. The silica group survived longer than the saline group. These results suggest that Ia antigen positive macrophages in the acute phase act as antigen-presenting cells and play an important role in the production of antibodies to self-AChR in the chronic phase.

Animals↗
PubMed1988

Thermostable DNA polymerase chain amplification of t(14;18) chromosome breakpoints and detection of minimal residual disease.

Achieving the capacity to detect minimal numbers of neoplastic cells is a major cancer diagnostic challenge. Chromosomal translocations such as the t(14;18)(q32;q21) found in follicular and some nonfollicular lymphomas provide a tumor-specific molecular marker. The 14;18 breakpoints are focused at one of six immunoglobulin heavy chain joining (JH) regions on chromosome 14 and a small major breakpoint region (MBR) of the BCL2 gene on chromosome 18. We utilized universal oligonucleotide primers of a region 5' to the BCL2 MBR and at the 3' end of JH segments to initiate a DNA polymerase chain reaction that amplified these BCL2-JH junctures. Use of thermostable DNA polymerase enabled annealing and synthesis steps at temperatures approaching the melting point of the primers, providing a sensitive and specific assay capable of detecting 1 lymphoma cell in 10(6) normal cells. This technique identified the subclinical presence of leukemic cells in all seven patients examined, including two in clinical remission. It also assessed the effectiveness of protocols designed to purge malignant cells from marrow. Moreover, this approach enabled the rapid DNA sequencing of chromosomal breakpoints without their molecular cloning. This assay markedly refines the capacity to detect minimal residual disease and should improve the ability to determine the stage of disease, stratify treatment, and evaluate therapy.

Bacterial Proteins↗
PubMed1987

Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners.

To elucidate the mechanism of the t(14;18)(q32;q21) chromosomal translocation found in follicular lymphoma, we examined the structure of both derivative (der) chromosomal breakpoints as well as their germ-line predecessors. We noted that chromosome segment 18q21 was juxtaposed with immunoglobulin heavy (H) chain gene diversity (DH) regions on all five der(18) chromosomes we examined, and we confirmed the juncture with immunoglobulin H-chain gene joining (JH) regions on the der(14) chromosome. However, the t(14;18) was not fully reciprocal in that chromosome 14 DNA between the DH and JH regions was deleted. Furthermore, extra nucleotides, reminiscent of "N" segments, were present at the der(14) and possibly der(18) junctions. This indicates that despite the mature B-cell phenotype of follicular lymphoma, the t(14;18) occurs during attempted DH-JH joining, the earliest event in immunoglobulin rearrangement in a pre-B-cell. Our detailed analysis of the germ-line 18q21 region indicated that most breakpoints clustered within a 150-base-pair major breakpoint region. However, we found no evidence for evolutionarily conserved immunoglobulin-like recombinational signals at 18q21, arguing against a role for immunoglobulin recombinase in chromosome 18 breakage. Instead, a direct repeat duplication of chromosome 18 sequences was discovered at both chromosomal junctures, typical of the repair of a naturally occurring staggered double-stranded DNA break. These results prompt a translocation model with illegitimate pairing of a staggered double-stranded DNA break at 18q21 and an immunoglobulin endonuclease-mediated break at 14q32 and with N-segment addition, repair, and ligation to generate der(14) and der(18) chromosomes.

Base Sequence↗
PubMed1987

Expression of Bcl-2 and Bcl-2-Ig fusion transcripts in normal and neoplastic cells.

We examined the expression of the Bcl-2 gene at chromosome segment 18q21, that is translocated into the Ig heavy chain gene locus in t(14;18) bearing lymphomas. Bcl-2, while B cell associated, is expressed in a variety of hematopoietic lineages including T cells. Bcl-2 mRNA levels are high during pre-B cell development, the time at which the t(14;18) translocation occurs, but are down regulated with maturation. Like certain other oncogenes, Bcl-2 is quiescent in resting B cells but up-regulated with B cell activation. Mature B cell lymphomas with a t(14;18) have log-folds more mRNA than matched counterparts without the translocation. A sensitive S1 protection assay revealed that all transcripts in t(14;18) B cells were Bcl-2-Ig fusion mRNAs and originated from the translocated allele. Thus, there is a marked deregulation of Bcl-2 when it is introduced into the Ig locus in t(14;18) lymphomas.

B-Lymphocytes↗
PubMed1986

Development of multiple organ-localized autoimmune diseases in nude mice after reconstitution of T cell function by rat fetal thymus graft.

Restoration of T cell function of athymic BALB/c nu/nu mice was investigated after transplantation of xenogeneic thymic rudiments from 15-d-old embryonic rats into kidney subcapsule. The rudiments developed well and formed a proper thymus structure composed of donor epithelia and host lymphocytes. Examination of antibody responses to SRBC revealed that approximately half the normal number of indirect PFCs were observed. Skin grafts from syngeneic BALB/c mice and thymic donor rat strains were accepted, whereas those from allogeneic mice and the rats of other than donor strains were vigorously rejected. Thymus-grafted nude mice under a conventional environment survived without any evident infectious diseases. Histological and immunofluorescence studies, however, showed a high incidence of multiple organ-localized autoimmune diseases in thyroid, salivary gland, stomach, adrenal, prostate, ovary, and testis in mice that produced the corresponding autoantibodies. These results together suggested that rat thymic grafts reconstituted T cell functions of nu/nu mice to a considerable degree, but that organ-localized autoimmune diseases developed, probably because certain auto-antigens of the recipients were recognized by the newly reconstituted host immunity.

Animals↗
PubMed1986

Effector mechanism in antitumor activity of monoclonal antibodies produced against an ascitic mouse mammary tumor.

Therapeutic effects of monoclonal antibodies with different immunoglobulin classes, detecting the same antigenic determinant of tumor specific antigen expressed on ascitic mouse mammary tumor MM46, were examined. With i.v. administration of gamma 2a, gamma 2b, or gamma 1 antibody we were able to keep a significant proportion of mice tumor free against i.p. inoculation of 5 X 10(4) MM46 cells with doses as small as 0.5 micrograms, but with administration of mu, gamma 3, or alpha antibody we were not able to keep mice tumor free with doses up to 5 micrograms. With 200 micrograms of antibody, however, an antitumor effect was observed even with mu or gamma 3 antibody, although alpha antibody still showed no effect at all. The therapeutic effect of gamma 2a was further examined in mice challenged with an increasing dose of tumor cells, and a significant effect was demonstrated against 1 X 10(6) cells with 200 micrograms of antibody but not against 5 X 10(6) cells. To assess the effector cells in antitumor activity of antibody in vivo, a histological examination of the tumor cells treated with each class of antibody was carried out. The tumor treated by gamma 2a antibody revealed a remarkable cell infiltration consisting predominantly of mononuclear cells, whereas those treated by mu, gamma 3, or alpha antibody did not. The tumor cells treated by gamma 1 or gamma 2b antibody showed a moderate cellular reaction. Next, a Winn assay was carried out in athymic C3H/HeN-nu/nu mice using gamma 2a antibody. A significant antitumor effect was observed even in those mice, indicating that T-cells are not predominant effector cells. The role of macrophages was studied in mice treated with two macrophage toxic agents, carrageenan and silica particles. These agents were shown to reduce the antitumor effect of gamma 2a antibody in both Winn assays and therapeutic experiments. Thus, histological examination and the blocking effect of macrophage toxic agents suggested the participation of host macrophages as effector cells in antibody-mediated tumor cell suppression in vivo.

Animals↗
PubMed1986

T cell receptor beta chain gene rearrangements in leukemias with immature T cell phenotype.

The arrangements of the T cell receptor (TCR) beta genes were studied in leukemias with immature T cell phenotype. Three cases of acute lymphocytic leukemia (ALL) and one case of chronic myelocytic leukemia in blastic crisis (CML-BC), which expressed only Tp40 antigen of cluster of differentiation (CD) 7 without erythrocyte rosette receptor (E), did not show rearrangements of TCR beta chain genes. Two of 5 ALL cases which expressed an additional T cell antigen, T1 of CD5, showed rearrangements of TCR beta genes. Two cases of CML-BC expressing T1 and Tp40, however, had unrearranged TCR beta genes. The results altogether showed that a part of E- T1+ Tp40+ ALL cases is of T cell origin.

Blast Crisis↗