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Biomedical subjects

M Seto

Publications and source records attributed to M Seto.

At least 217 records · Page 12Linked to original sources

bcl-2 translocation in Japanese B cell lymphoma: novel bcl-2 translocation with immunoglobulin heavy chain diversity segment.

Breakpoints of a lymphoma case with bcl-2 gene rearrangement that did not show comigration of immunoglobulin (Ig) heavy chain joining (JH) fragment were cloned. Sequence analysis revealed that the translocation broke the 3' side of the Ig heavy chain diversity (DH) segment at the heptamer recombination signal and each end was ligated to the bcl-2 locus. Since Southern blot demonstrated that both alleles of JH were rearranged, this translocation was suggested to have occurred at the step of VH-DH, or DH-DHJH recombination, one step later than that of DH-JH recombination where the common pattern of bcl-2 rearrangement generally occurs. Cases that showed comigration with JH fragment were also studied by polymerase chain reaction with 5' bcl-2 oligomer and 3' JH consensus anti-sense oligomer since it has been demonstrated that bcl-2 translocation at the major breakpoint clustering region (mbr) in American cases clusters within an about 150 bp region in the mbr. The results demonstrated that four out of five cases studied were amplified, indicating that the same clustering mechanism exists for Japanese cases. The present study, together with our previous report on Ig kappa-bcl-2, indicated that bcl-2 translocation in Japanese B cell lymphomas might occur at a later stage of B cell development, as compared with that in American cases. Less involvement of bcl-2 in Japanese B cell lymphoma may also be in part explainable by low susceptibility to bcl-2 rearrangement at the step of DH-JH recombination.

Base Sequence↗

[Clinical evaluation of serological antigen detection tests for candidemia].

The new serological tests for candidemia were evaluated. In nine cases of candidemia, fungal index (Endotoxin D-Endospecy) was 146.8 +/- 116.8 pg/ml and D-arabinitol/creatinine 1.10 +/- 1.04 mumol/mg. Fungal index was significantly (p less than 0.01) higher in candidemia than suspected infections. All candidemia were positive for Cand-Tec latex agglutination, but twelve of the sixteen cases of suspected infections were also positive. Mannan latex agglutination was very specific for candidemia. Four cases of candidemia was positive for Mannan latex agglutination and only one case was positive in suspected infections. Fungal index and D-arabinitol/creatinine was decreased after treatment of antifungal agents. In poor clinical efficacy case, these titer remained high even after treatment. These data suggested the usefulness of these serological tests for candidemia.

Adolescent↗

[The relationship between the aortic pulse wave velocity and osteoporosis in elderly women].

The relationship between arteriosclerosis and osteoporosis (OP) was assessed in 20 elderly women. The aortic pulse wave velocity (PWV) was used as the index of arteriosclerosis and bone mineral content (BM) of the vertebral body, which was measured by quantitative computed tomography, was used as an index of OP. PWV and BM showed a significant correlation with aging (PWV and age: r = 0.466, p less than 0.05, BM and age: r = -0.487, p less than 0.05). In the group in which the serum alkaline phosphatase (ALP) was higher than 180 IU/l (n = 11), there was a significant inverse correlation between PWV and BM (r = -0.728, p less than 0.02). On the other hand, there was no correlation between PWV and BM in the group in which ALP was lower than 180 IU/l (n = 9). These results suggest that in cases with OP and high levels of ALP, calcium (Ca) seems to be released from the bone system and transferred to the wall of the aorta. The mechanism and pathogenesis of this Ca transference is unknown and should be investigated.

Aged↗

[A case of aortitis syndrome complicated with amyloidosis, type AA].

We recently saw a patient who had aortitis syndrome associated with secondary amyloidosis. To our knowledge, she is the fourth report of this complication occurring in aortitis syndrome. In November 1985, the patient, a 18 year-old woman, was admitted to our hospital because of a high fever, back pain, abdominal pain and general fatigue. On physical examination, bruit was audible on the abdomen, bilateral radial artery was weakly palpable. Angiography showed the stenosis of bilateral carotid artery, subclavian artery, renal artery and superior mesenteric artery. From the above findings, she was diagnosed aortitis syndrome, and treatment was begun with prednisolone. However, she developed recurrently a high fever, chest pain, abdominal pain and exertional dyspnea. Laboratory findings at the active stage revealed the marked elevation of leukocytes, erythrocyte sedimentation rate and C-reactive protein. On her clinical course, the number of circulating thrombocytes was paralleled with the activity of the disease. On June 1988, she developed suddenly a high fever and severe pain of abdomen. Pathological findings of her stomach showed the deposition of amyloid protein A. Laboratory findings depicted the marked increment of thrombocytes, beta-thromboglobulin and platelet factor 4. These results suggest that circulating thrombocytes may play a role in product ion of amyloid protein.

Adult↗

[bcl-2 gene in B cell lymphoma].

In t(14;18) lymphomas, bcl-2 gene is activated by the juxtaposition of immunoglobulin (Ig) gene. The fused bcl-2-Ig gene generates chimeric mRNAs which consist of bcl-2 at 5' side and Ig at 3' side. Chimeric mRNA does not disrupt the bcl-2 coding frame of 239 amino acid polypeptide. Activated bcl-2 gene introduced in normal B lymphoblastoid cells (LCL) demonstrated an increased cloning efficiency in soft agar but failed to confer tumorigenicity to LCLs as a single agent. bcl-2 gene rearrangement in Japaneses B cell lymphoma was studied and found that 10 out of 32 cases of follicular lymphoma (31%) and 5 out of 56 cases of diffuse lymphoma (9%) were rearranged, suggesting less frequency of B cell lymphoma, particularly follicular lymphoma in Japan is partly due to less bcl-2 involvement than American cases. Three cases out of 15 cases with bcl-2 rearrangement demonstrated a unique pattern of rearrangement. Two cases of the three were analysed and found that both cases were translocated at the later step than DH-JH joining of Ig rearrangement. Thus, bcl-2 translocation in Japanese B cell lymphomas might occur at the later stage of B cell development, when compared with that in American cases. Less involvement of bcl-2 in Japanese B cell lymphoma may be explained by low susceptibility to bcl-2 rearrangement at the step of DH-JH recombination.

Chromosomes, Human, Pair 14↗

[Lung ventilation imaging with TECHNEGAS: clinical study of lung deposition and ventilation/perfusion].

In order to optimize inhalation method for lung ventilation imaging with Tc-99m-gas (TECHNEGAS), relation between lung deposition of TECHNEGAS and inhalation method was evaluated. Submaximal inhalation with breath-holding (BH), continuous submaximal inhalation (C) and tidal inhalation (TV) were compared in 35 patients (36 studies) with various lung diseases. Mean lung deposition of TECHNEGAS was 6.6-7.4%/LD in BH group and was significantly higher than other groups of inhalation method (p less than 0.05-0.001). Lung deposition increased according to the times of inhalation in C group. TV group resulted in the lowest lung deposition which was same as 5 times of inhalation in C group. Lung/filter ratio (L/F) was highest in BH group. Image quality of TECHNEGAS was significantly better in BH group. Hot spot in central airway was seen in 15% of patients. All of them was in TV or C groups. In order to improve lung deposition and image quality of the TECHNEGAS, sufficient breath-holding was important. L/F seemed to be the index of effective inhalation of the TECHNEGAS. TV was suitable for poorly cooperative or dyspneic patients. TECHNEGAS was useful for evaluation of lung ventilation to provide good quality image with safety and simplicity.

Administration, Inhalation↗

[BCL-2 gene in lymphocytic malignancy].

In t(14;18) (q32;q21) lymphomas, bcl-2 gene is activated by the juxtaposition of immunoglobulin (Ig) gene. The fused bcl-2-Ig gene generates chimeric mRNAs which consist of bcl-2 at 5' portion and Ig at 3' portion. Chimeric mRNA does not disrupt the bcl-2 coding frame of 239 amino acid polypeptide. Bcl-2-Ig transgenic mice demonstrated the extended B cell survival and the follicular lymphoproliferation, but they did not develop a malignancy until 25 weeks. Ten percent of them, however, developed malignant diffuse large-cell lymphomas after a long latency. Forty percent of these malignancies demonstrated the c-myc rearrangement, indicating that multiple step changes are required for malignant transformation in bcl-2 activated cells. Study on the bcl-2 gene rearrangement in Japanese B cell lymphoma and B-CLL revealed that 10 out of 32 cases of follicular lymphoma (31%), 5 out of 56 cases of diffuse lymphoma (9%) and 2 out of 30 cases of B-CLL (7%) were rearranged. Less frequency of B cell lymphoma, particularly follicular lymphoma in Japan might be partly due to the less bcl-2 involvement than in American cases. The ratio of bcl-2 involvement in B-CLL is not significantly different between Japan and U.S.A.. bcl-2 rearrangement at 5' promoter region is noted for Japanese B-CLL which was demonstrated for American cases. The clinical application of polymerase chain reaction for bcl-2 translocation was also discussed.

Animals↗

Diphosphorylation of myosin light chain in smooth muscle cells in culture. Possible involvement of protein kinase C.

Prostaglandin (PG) F2 alpha (30 microM) stimulated both monophosphorylation and diphosphorylation of myosin light chain (MLC) in a smooth muscle cell line (SM-3). The diphosphorylation was significantly decreased by treatment with the protein kinase C inhibitor staurosporine (30 nM, 30 min) from 20.1% of total MLC to 4.5%. The protein kinase C down-regulation treatment of SM-3 cells with phorbol dibutyrate suppressed to 8.7% the MLC diphosphorylation activity in the SM-3 cells. This down-regulation treatment had little effect on the monophosphorylation. We propose that the MLC diphosphorylation in PGF2 alpha-stimulated SM-3 cells in culture may be regulated through mechanisms sensitive to protein kinase C.

Animals↗

Stimulus-specific patterns of myosin light chain phosphorylation in smooth muscle of rabbit thoracic artery.

When the rabbit thoracic artery was stimulated with submaximal concentrations of agonist [40 mM K+, 30 microM prostaglandin F2 alpha (PGF2 alpha) or 7 microM histamine], about 90% of a maximal contraction occurred. Each agonist induced a rapid development of contraction followed by a sustained response. The maximal rate of force generation stimulated with PGF2 alpha was twice that seen with K+ or histamine. Stimulation with 40 mM K+ increased the extent of monophosphorylated 20 kDa myosin light chain (MLC-P) for up to 1 min to a maximal value of 38.8 +/- 1.0%, there was a subsequent rapid decrease and the MLC-P level remained just above the basal value for 40 min (6.8 +/- 3.0%). In the case of stimulation with 7 microM histamine, MLC-P level increased rapidly and was sustained for up to 40 min (28.0 +/- 4.9%). In contrast to the stimulation with K+ or histamine, PGF2 alpha induced both mono- and diphosphorylated MLC20 (MLC-P and MLC-P2 respectively) at a low concentration (3 microM). The monophosphorylation of MLC20 induced by 30 microM PGF2 alpha reached the maximal value of 32.8 +/- 5.2%, and was sustained for up to 40 min (15.2 +/- 5.4%). The diphosphorylation of MLC20 increased rapidly (7.4 +/- 4.0% at 5 min), then decreased to the basal value within 40 min. These results suggest that different modes of stimulation of smooth muscle contraction produce different profiles of MLC20 phosphorylation. The implications of these observations are that the diphosphorylated form, specifically induced by certain agents, may modify the mode of contraction of the aortic artery.

Animals↗

Genuine CD7 expression in acute leukemia and lymphoblastic lymphoma.

CD7 has been used as a valuable marker for normal and malignant T cells and also for a proportion of acute nonlymphocytic leukemia (ANLL) cells. Difference in reactivity was noticed among CD7 antibodies, however, when tested against ANLL cells and myeloid/monocytoid cell lines; Tp40 antibody produced in our laboratories was not reactive with the HL-60 promyelocytic line, whereas 4A antibody was reactive, even though both detected a quite similar or an identical epitope on CD7 molecule. Preincubation of HL-60 cells with human immunoglobulin preparation clearly negated the reactivity by 4A, suggesting that 4A antibody is not reactive to CD7 itself, but it probably binds with immunoglobulin G Fc receptors expressed on HL-60 cells. Five cases of ANLL which were positive with 4A antibody were selected and tested with Tp40 antibody, and only two were found to be positive. Expression of CD7 mRNA in these two cases (but not in other cases) was also demonstrated by Northern blotting with a cDNA probe for CD7 recently cloned in our laboratories, indicating that CD7 is expressed on a certain fraction of ANLL, although the positive cases may be smaller than the reports so far appeared. A Northern blot study was also conducted with two acute lymphocytic leukemia cases and one lymphoblastic lymphoma case with CD7+, CD2-/+/-, CD5-/+/- phenotype and germline T cell receptor beta genes. CD7 mRNA is expressed in all three cases and CD3 mRNA is also observed in two cases, suggesting that these tumor cells are of T precursor origin.

Acute Disease↗

Alteration in the myosin phosphorylation pattern of smooth muscle by phorbol ester.

Pretreatment with a high concentration of phorbol 12-myristate 13-acetate (PMA, 100 nM) increased the degree of tension and extent of myosin light chain (MLC20) phosphorylation in the K(+)-stimulated rabbit aortic artery. Pretreatment with 100 nM PMA did not alter the relationship between MLC20 phosphorylation and the tension seen with K+ stimulation in the initial phase and steady state of contraction. However, a low concentration of PMA (10 nM) potentiated only the MLC20 phosphorylation during the steady state of contraction with no effect on the tension. In contrast, the prostaglandin (PG) F2 alpha-induced tension development and the MLC20 phosphorylation were not affected by PMA pretreatment at both low and high concentrations. The inhibitory action of nifedipine on the K(+)-induced contraction was not affected by pretreatment with 100 nM PMA; the concentration producing half-maximal inhibition of nifedipine for the K(+)-induced contraction (33 nM) was the same as that of the K+ plus 100 nM PMA-induced contraction (32 nM). Our results suggest that PMA may increase the level of myosin light chain kinase-dependent MLC20 phosphorylation and the tension in the K(+)-stimulated artery, an effect which differs from that seen with increases in K+ concentrations. The regulatory mechanism for the contraction involving PGF2 alpha stimulation may differ from that seen in the case of K+ stimulation.

Animals↗

[The relationship of osteoporosis to mitral annular and aortic valvular calcification in elderly women].

Mitral annular calcification (MAC) and aortic valve calcification (AVC) are thought to be attributable to the aging process, and their incidences are especially high in elderly women. It is known that the incidence of osteoporosis (OP) is also relatively high in elderly women. Therefore, we investigated the relationship of OP to MAC and AVC. The study subjects were 39 women aged 70-89 years. MAC and AVC were investigated by echocardiography. The amount of bone mineral (BM) in the lumbar vertebral bone was measured by computed tomography using a bone phantom and the standard amount of CaCO3. MAC and AVC were detected in 14 (35.9%) and 19 (48.7%) of the 39 subjects, respectively, and there was a tendency of coexistence of MAC and AVC. There was no significant age difference between patients with and without MAC. The amount of BM was significantly lower in patients with MAC than in patients without it (27.1 +/- 8.2 vs 53.5 +/- 27.3 mg/cm3: p less than 0.01). There was no correlation between the amounts of BM and AVC. In conclusion, the amount of BM is clearly lower in elderly women with MAC, suggesting that MAC may be related to OP etiologically. However, there was no clear relationship between AVC and OP. Thus, the etiologies of AVC and MAC may be different.

Aged↗

Evaluation of inferior mesenteric vein blood flow circulation with per-rectal administration of thallium-201 and technetium-99m pertechnetate.

We administered both per-rectal thallium-201 (201Tl) and technetium-99m pertechnetate (99mTc) to patients with liver diseases in order to understand the abnormalities of inferior mesenteric vein (IMV) blood flow circulation. As 201Tl heart-to-liver uptake ratio (H:L), reflecting the degree of portal-systemic shuntings (PSS), increased, the visualization of IMV in general became poor on 99mTc scintigrams. 201Tl H:L in the group with no visualization of IMV on 99mTc scintigrams was significantly higher than in the group with clear visualization of IMV (p less than 0.001). However, there were patients who showed IMV visualization among those with high 201Tl H:L. In these patients, it was considered that IMV blood flowed in the normograde direction, escaping mainly through PSS at the upper part of the portal system, and resulting in elevated H:L. In the patients without IMV visualization, IMV blood flowed in the retrograde direction, escaping mainly through collaterals at the lower part of IMV. Inferior vena cava (IVC) was visualized on 99mTc scintigrams in some patients without IMV visualization, indicating the presence of collaterals from the distal part of IMV to IVC. Per-rectal studies using these two radiotracers can afford us useful informations on the abnormalities of IMV blood flow hemodynamics in patients with liver diseases.

Adult↗

Growth- and tumor-promoting effects of deregulated BCL2 in human B-lymphoblastoid cells.

Human follicular B-cell lymphomas possess a t(14;18) that translocates a putative protooncogene, BCL2, into the immunoglobulin heavy chain locus. The normal BCL2 gene is quiescent in resting B cells, expressed in proliferating, but down-regulated in differentiated B cells. Inappropriately high levels of BCL2-immunoglobulin chimeric RNA are present in t(14;18) lymphomas for their mature B-cell stage. We examined the biologic effects of BCL2 deregulation in human B cells by introducing BCL2 into human B-lymphoblastoid cell lines (LCLs) with retroviral gene transfer. Although deregulated BCL2 expression as a single agent was not sufficient to confer tumorigenicity to LCLs, it consistently produced a 3- to 4-fold increment in LCL clonogenicity in soft agar. In addition, BCL2 deregulation complements the transforming effects of the MYC oncogene in LCLs. BCL2 augmented the clonogenicity of LCLs bearing exogenous MYC and increased the frequency and shortened the latency of tumor induction in immunodeficient mice. These results demonstrate a role for BCL2 as a protooncogene that affects B-cell growth and enhances B-cell neoplasia.

Animals↗

bcl-2 gene rearrangement analysis in Japanese B cell lymphoma; novel bcl-2 recombination with immunoglobulin kappa chain gene.

The rearrangement of bcl-2 gene was studied in 56 Japanese B cell lymphoma cases to investigate the contribution of bcl-2 gene to lymphomagenesis in Japan. Ten out of 56 cases showed bcl-2 gene rearrangement; it was detected in only 5 out of 16 follicular lymphoma cases (31%) and in 5 out of 40 diffuse B cell lymphoma cases (13%). The incidence of bcl-2 gene involvement in Japanese follicular lymphomas was lower than those reported in the United States. This might contribute to the lower incidence of follicular lymphoma cases in Japan. Novel recombination between bcl-2 and Ig kappa genes at the 5' region of bcl-2 and J kappa 4 segment was observed in one follicular lymphoma case, suggesting that bcl-2 gene is transcriptionally activated by Ig kappa enhancer. It was also suggested that this case had originated from a more differentiated B cell than most follicular lymphomas with bcl-2-Ig H recombination.

B-Lymphocytes↗

[Assessment of split renal function before and after angioplasty or bypass grafting in the patients with renovascular hypertension].

Two different methods to assess the change of split renal function following angioplasty or bypass grafting were studied in a total of 12 patients with renovascular hypertension. The studies were performed before and within seven days after the therapeutic intervention. Split effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) after injections of I-131 hippuran and Tc-99m DTPA were measured using kidney counting corrected for depth and dose, described by Schlegel and Gates. In six of 10 patients with unilateral renal artery stenosis and in two patients with bilateral renal artery stenoses (two of 4 affected kidneys), the split renal function was improved after the therapeutic intervention, in accordance with the drop in blood pressure and the reduction of plasma renin activity. The improvement in ERPF and GFR was more likely in the patients without severely reduced renal function. In such patients, the improvement in ERPF was more pronounced than that in GFR. And in two patients with functional improvement, the Captopril-induced reduction of split GFR in the affected kidney was disappeared after the intervention. Moreover, in the long-term follow-up of three patients with functional improvement, one patient showed the deterioration of split renal function suggesting the relapse of renal artery stenosis. These results suggest that the combined studies of split ERPF and GFR determinations can be useful to evaluate the therapeutic effect as well as the presence or absence of functional improvement after the intervention.

Angioplasty, Balloon↗

[Angiotensin II-induced hypertension chemotherapy of bone and soft-tissue sarcomas].

We treated 14 patients with high grade sarcomas by angiotensin II-induced hypertension chemotherapy. The chemotherapy protocol described by Rosen was selected according to histological classification of sarcomas (small cell sarcoma, spindle cell sarcoma, pleomorphic sarcoma). The level of angiotensin-induced hypertension was one and half times as high as blood pressure at rest. Induced hypertension was maintained for 30-60 minutes. In three cases of 5 primary osteosarcomas, induced hypertension resulted in the increase of tumor stain and/or vascularity angiographically, and chemotherapeutic effects were CR or PR. The six cases with soft-tissue sarcomas were 2 cases each of CR, PR, and NC. The decrease of relative tumor blood flow under the condition of angiotensin II-induced hypertension was detected in 5 cases of 6 soft-tissue sarcomas by 133Xe clearance method. In the case of rhabdomyosarcoma, the decrease of tumor stain and vascularity by induced hypertension was observed on angiogram. As the side effects accompanying induced hypertension, nausea and chest oppression were noted in 2 cases, respectively. In this study it was suggested that angiotensin II-induced hypertension chemotherapy was effective for osteosarcoma, but that it might be ineffective for soft-tissue sarcomas.

Adolescent↗