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Biomedical subjects

S Sakamaki

Publications and source records attributed to S Sakamaki.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Pure red cell aplasia induced by clomipramine hydrochloride in a patient with SLE].

A 48-year-old woman, who had been suffering from systemic lupus erythematosus (SLE), developed normochromic normocytic anemia after receiving clomipramine hydrochloride. Her reticulocyte count was low, and a bone marrow aspirate revealed erythroid hypoplasia without involvement of other cell lines. Thus a diagnosis of pure red cell aplasia (PRCA) was made. The anemia gradually resolved following withdrawal of the drug. Although several drugs are known to cause PRCA, this is the first time that clomipramine hydrochloride has been reported to have such an effect. The underlying SLE in this case suggested the possible immunological pathogenesis of drug-induced PRCA.

Antidepressive Agents, Tricyclic↗
PubMed2000

[Sézary syndrome showing a stable clinical course for more than four years after oral administration of etoposide and methotrexate].

A 62-year-old woman was admitted because of leukocytosis, systemic lymph node swelling and erythroderma. Laboratory data disclosed a WBC count of 15,600/microliter (CD4-positive cells: 91%). CD25 and HTLV-1 were negative. A skin biopsy revealed the involvement of T cells. These data and findings were consistent with a diagnosis of Sézary syndrome. Although the patient was treated with 2 courses of CHOP, the leukocyte count did not decrease. We then treated the patient orally with etoposide (25 mg/day) and methotrexate (10 mg/week), and this resulted in reduction of the leukocyte count and lymph node swelling, and amelioration of the erythroderma. As Sézary syndrome is an extremely rare disease, it is worthwhile reporting cases like the present one, where therapy was successful.

Administration, Oral↗
PubMed2000

A case of diffuse large B-cell lymphoma transformed from immunoglobulin A-producing marginal zone B-cell lymphoma.

We present a rare case of diffuse large B-cell lymphoma transformed from immunoglobulin (Ig) A-secreting marginal zone B-cell lymphoma. A 62-year-old woman was admitted to our hospital for examination of a disseminated pulmonary shadow. Gradual swelling of bilateral axilla and right inguinal lymph nodes were noted after admission. Histological examination of the lymph node biopsy specimen revealed the appearance of marginal zone B-cell lymphoma. The surface Ig of lymphoma cells was IgA-kappa, which coincided with the class of monoclonal Ig found in the patient's serum. The lymph node swelling and pulmonary shadow subsided, and the serum IgA level was normalized by 3 courses of systemic chemotherapy. However, after 4 courses of treatment, new tumor lesions at the right chest wall and left arm progressively became apparent. The biopsy specimen of the tumor showed a feature of diffuse large B-cell lymphoma. Despite intensive chemotherapy, the patient died of spreading tumor burden into the central nervous system.

Cell Transformation, Neoplastic↗
PubMed2000

[Retardation of platelet recovery after autologous stem cell transplantation in a patient with acute lymphoblastic leukemia: possible role of decreased thrombopoietin production by bone marrow stromal cells].

A 16-year-old boy was diagnosed as having acute lymphoblastic leukemia and underwent autologous stem cell transplantation at the time of his second complete remission. Retardation of platelet recovery was evident at day 90 (< 5 x 10(4)/microliter), and at day 660 after transplantation the platelet count was 8.5 x 10(4)/microliter. Neutrophils and RBCs showed only slightly retarded recovery. Bone marrow stromal cells, which are thought to play an integral role in megakaryopoiesis, were examined. Although TPO mRNA expression per cell was normal, CFU-F was significantly decreased, resulting in a decrease of total TPO mRNA expression. In contrast, expression of G-CSF mRNA per cell was increased. It was thought that chemotherapy before bone marrow transplantation may have reduced the number of stromal cells, leading to retardation of platelet recovery because of low TPO expression.

Adolescent↗
PubMed2000

[Severe hemolysis and SIADH-like symptoms induced by vincristine in an ALL patient with liver cirrhosis].

An 11-year-old boy was diagnosed as having acute lymphoblastic leukemia (ALL, L1) in 1987 and underwent treatment with an ALL high-risk protocol (prednisolone, vincristine (VCR), daunorubicin, 1-asparaginase), which resulted in complete remission. In 1990 he developed chronic hepatitis C and received interferon therapy. In December 1994, ALL recurred, and the patient was treated with VCR. He subsequently developed severe hemolysis (Hb 12.5 g/dl-->6.8 g/dl) with increases of indirect bilirubin, AST, and LDH. Furthermore, symptoms resembling a syndrome of inappropriate secretion of ADH (SIADH) and DIC developed. Upon incubation of the patient's red blood cells with VCR in vitro, extreme deformity of the cells was observed. These findings suggested that splenomegaly, due to liver cirrhosis which had developed rapidly from chronic hepatitis C while the patient was in an immunosuppressed state induced by anticancer drugs, had trapped the deformed red blood cells and resulted in severe hemolysis. The patient died on the 165th day after admission due to liver failure.

Adolescent↗
PubMed1999

Transforming growth factor-beta1 (TGF-beta1) induces thrombopoietin from bone marrow stromal cells, which stimulates the expression of TGF-beta receptor on megakaryocytes and, in turn, renders them susceptible to suppression by TGF-beta itself with high specificity.

The present study was designed to test the concept that platelets release a humoral factor that plays a regulatory role in megakaryopoiesis. The results showed that, among various hematoregulatory cytokines examined, transforming growth factor-beta1 (TGF-beta1) was by far the most potent enhancer of mRNA expression of bone marrow stromal thrombopoietin (TPO), a commitment of lineage specificity. The TPO, in turn, induced TGF-beta receptors I and II on megakaryoblasts at the midmegakaryopoietic stage; at this stage, TGF-beta1 was able to arrest the maturation of megakaryocyte colony-forming units (CFU-Meg). This effect was relatively specific when compared with its effect on burst-forming unit-erythroid (BFU-E) or colony-forming unit-granulocyte-macrophage (CFU-GM). In patients with idiopathic thrombocytopenic purpura (ITP), the levels of both TGF-beta1 and stromal TPO mRNA were correlatively increased and an arrest of megakaryocyte maturation was observed. These in vivo findings are in accord with the aforementioned in vitro results. Thus, the results of the present investigation suggest that TGF-beta1 is one of the pathophysiological feedback regulators of megakaryopoiesis.

Bone Marrow↗
PubMed1999

Enhanced inhibition of experimental metastasis by the combination chemotherapy of Cu-Zn SOD and adriamycin.

We previously reported that reactive oxygen species (ROS) enhance tumor cell metastasis, and by administration of recombinant human superoxide dismutase (rh SOD), an enzyme which scavenges O2- successfully reduced lung metastasis of mouse MethA sarcoma and Lewis lung carcinoma. These observations suggested that rh SOD suppressed tumor cell invasion by eliminating O2- the primary source of ROS. However, for the clinical application of the drug as an anti metastatic agent, rh SOD needs to be administered in combination with other cytotoxic agents, since SOD by itself has no cytotoxic activity. In this paper, we investigated the effectiveness of the combination chemotherapy of rh SOD and adriamycin (ADR), an anti-cancer agent against the experimental metastasis of highly metastatic clone, MH-02, which was derived from murine Meth A sarcoma. The present metastasis experiment clearly indicates that the administration of rh SOD enhances the antimetastatic effect of ADR. On the other hand, we found that the inhibition rate of metastasis exhibited by the combination chemotherapy of rh SOD and a certain dose (5 mg/ml) of ADR was inferior to that of rh SOD. This apparent paradoxical phenomenon was presumably explained by our finding that tumor cells themselves augment their invasive capacity and platelet aggregation, both of which are causative factors for metastasis formation, by generation of O2- when they were treated with ADR. Nevertheless, the combination chemotherapy of SOD with anticancer drugs such as ADR can be a practical anti-metastasis strategy.

Animals↗
PubMed1999

Systemic lupus erythematosus with a giant rectal ulcer and perforation.

A 41-year-old man with systemic lupus erythematosus (SLE) who developed pelvic inflammation due to perforation of a giant rectal ulcer is described. The patient presented with persistent diarrhea, abdominal pain and fever without development of disease activity of SLE. Endoscopic and radiological examinations revealed a perforated giant ulcer on the posterior wall at the rectum below the peritoneal evagination. The ulcerated area was decreased after a colostomy was performed at the transverse colon to preserve anal function. The patient is currently being monitored on an outpatient basis. It should be noted that life-threatening complications such as perforated ulcer of the intestinal tract could occur without SLE disease activity.

Adult↗
PubMed1999

Use of PCR serum in diagnosing and monitoring cytomegalovirus reactivation in bone marrow transplant recipients.

We previously reported that the use of polymerase chain reaction (PCR) in detecting cytomegalovirus (CMV) DNA in serum (sPCR) enables the detection of CMV viremia, which has not been possible with other methods. In this study, the clinical usefulness of sPCR was investigated by comparison with the results of three other diagnostic methods, i.e., antigenemia assay (AG), shell vial culture test (shell vial), and complement-fixing (CF) antibody titer. The present study included 26 patients with hematological diseases who had undergone allogeneic bone marrow transplantation (BMT). A total of 347 samples were collected, and the results of the sPCR and AG methods were in agreement in 91.1% of the samples. When a subject was positive in both the sPCR and AG tests, and the other two tests (shell vial and CF) were also positive, CMV reactivation was surmised as definite. When only the result of the shell vial test or the CF test was positive, these results were taken as false-positives. The time at which the samples became positive in each of these four tests was 7.5 weeks post-BMT for sPCR, 7.0 weeks post-BMT for the AG test, 7.4 weeks post-BMT for the shell vial test, and 9.7 weeks post-BMT for the CF test. Thus, it was found that samples became positive at almost the same time for the sPCR, AG, and shell vial tests. Interstitial pneumonitis (IP) due to CMV developed in 3 subjects. These cases were positive in the sPCR, AG, and shell vial tests prior to the manifestation of symptoms of IP. The CF test did not become positive until after the onset of the disease. As the IP due to CMV was controlled with treatment, the sPCR and AG tests became negative. With the shell vial and CF tests, on the other hand, the test results continued to be positive even after the IP was cured. These findings demonstrate that the sPCR test method--like the AG test--yields few false-positive results. Therefore, the sPCR method is useful in early diagnosis of reactivation of CMV and for evaluation of the efficacy of therapy administered for IP. In addition, sPCR can be performed simultaneously on a large number of samples, and the evaluation of the test results is simple. We conclude that the sPCR test may be superior to the three other diagnostic methods for evaluation of serum samples from multiple institutions.

Adolescent↗
PubMed1999

[The control survey in CD marker analysis of leukemic cells].

Analysis of cell surface antigens is thought to be more objective compared to classification by the morphology. However, it has been indicated that the evaluated data are different each other between institutes. Therefore, we performed a control survey of CD marker analysis in leukemia cells using flow cytometry in six commercial laboratories. The expression of CD2, 4, 5, 7, 8, 10, 13, 14, 19, 20, 33, 34, 38, and 71, HLA-DR in tumor cells from megakaryoblastic leukemia, lymphoblastic crisis of CML, and ALL patients, were examined. There were large differences in the results of CD marker analysis among the six commercial laboratories. One possible reason for this result is the differences in gating condition and monoclonal antibodies used in each laboratory. However, there were the differences in the results even when the same gating condition and antibodies were used. The reasons for the difference in transport or treatment conditions for samples remain a matter of considerable controversy. In the present condition, it was suggested that the exchange of information about the origin of tumor cells between the physician in charge and examination experts is thought to be the best way to analyze proper cell surface antigen expression. Further, no national survey has been carried out, but the establishment of a standard assay is preferred to obtain proper data for the patients and medical parties concerned.

Adolescent↗
PubMed1999

A case of malignant lymphoma producing autoantibody against platelet glycoprotein Ib.

A 61-year-old woman was referred to our hospital for refractory thrombocytopenia (3 x 10(3)/microliter) and massive melena. Bone marrow aspiration revealed normal cellularity and increased megakaryocytes (250/microliter). An abdominal computerized axial tomography scan showed isodensity masses on both adrenal glands. 67 Ga-scintigraphy exhibited strong uptake into the bilateral adrenal tumor and mediastinal region. IgM-type antibody against platelet glycoprotein Ib (GpIb) was detected in the patient's serum. A needle biopsy of the right adrenal tumor was performed, and histology was non-Hodgkin's lymphoma (NHL), diffuse large B-cell type. Following the diagnosis of autoimmune thrombocytopenia associated with lymphoma, administration of corticosteroid (predonisolone 60 mg/day) and high-dose intravenous globulin (15 g/day x 4 days) was carried out, but neither was effective in normalizing the thrombocytopenia. Immunosuppressive therapy (cyclophosphamide 500 mg and 1 mg of vincristine) markedly restored the platelet counts to 7.2 x 10(4)/microliter and ceased the melena; furthermore, the size of adrenal tumors decreased by more than 60% after therapy. We cultured the lymphoma cells drawn by needle biopsy with IL-6 in vitro and found that the lymphoma cells produced IgM-type antiplatelet antibodies against platelet GpIb in the culture supernatant. Thus this is a rare case of NHL in which the production of antiplatelet antibody from lymphoma cells was confirmed in vitro.

Autoantibodies↗
PubMed1999

[Waldenström macroglobulinemia with diffuse large B-cell lymphoma that developed from a different B-cell clone].

A 62-year-old man was given a diagnosis of Waldenström macroglobulinemia (WM) in January 1995. He was treated with melphalan and corticosteroid until January 1996, when he experienced high fever and weight loss. The patient visited a nearby hospital, received a diagnosis of liver abscess, and was referred to our hospital on February 23, 1996. Computed axial tomographic scans demonstrated multiple isodensity masses in the liver, left adrenal region, and right kidney hilum. Needle biopsy specimens of a liver mass revealed infiltration of diffuse large B-cell lymphoma (REAL classification), suggesting that non-Hodgkin's lymphoma supervened WM. Despite multiple cycles of chemotherapy, the lymphoma responded poorly. The patient died of pneumonia and sepsis on May 10, 1996 and an autopsy disclosed broad involvement of liver and spleen with lymphoma. Southern blot analysis of DNA samples obtained from the patient's bone marrow at the time of the initial diagnosis of WM, and later from the needle biopsy specimen of liver mass, displayed different patterns of immunoglobulin heavy chain gene rearrangement. We therefore concluded that in this patient the lymphoma was not a progression of WM, but rather, an independent B-cell malignancy.

B-Lymphocytes↗
PubMed1998

Aberrant crypt foci of the colon as precursors of adenoma and cancer.

BACKGROUND: Aberrant crypt foci of the colon are possible precursors of adenoma and cancer, but these lesions have been studied mainly in surgical specimens from patients who already had colon cancer. METHODS: Using magnifying endoscopy, we studied the prevalence, number, size, and dysplastic features of aberrant crypt foci and their distribution according to age in 171 normal subjects, 131 patients with adenoma, and 48 patients with colorectal cancer. We also prospectively examined the prevalence of aberrant crypt foci in 11 subjects (4 normal subjects, 6 with adenoma, and 1 with cancer) before and after the administration of 100 mg of sulindac three times a day for 8 to 12 months and compared the results with those in 9 untreated subjects (4 normal subjects and 5 with adenoma). All 20 subjects had aberrant crypt foci at base line. RESULTS: We identified 3155 aberrant crypt foci, 161 of which were dysplastic; the prevalence and number increased with age. There were significant (P<0.001) correlations between the number of aberrant crypt foci, the presence of dysplastic foci, the size of the foci, and the number of adenomas. After sulindac therapy, the number of foci decreased, disappearing in 7 of 11 subjects. In the untreated control group, the number of foci was unchanged in eight subjects and slightly increased in one (P<0.001 for the difference between the groups). CONCLUSIONS: Aberrant crypt foci, particularly those that are large and have dysplastic features, may be precursors of adenoma and cancer.

Adenoma↗
PubMed1998

Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells.

The function of bone marrow (BM) stromal thrombopoietin (TPO) in megakaryopoiesis remains unknown. In the present study we attempted to clarify the pathophysiological implications of stromal TPO in normal subjects (NS) and in patients with idiopathic thrombocytopenic purpura (ITP), aplastic anemia (AA), and essential thrombocythemia (ET) by measuring TPO concentrations in BM and peripheral blood (PB) and by estimating the levels of stromal TPO mRNA with TaqMan fluorescence-based post-reverse transcription-polymerase chain reaction product detection system. The results showed that TPO concentrations in PB were significantly elevated in patients with ITP (34.9 +/- 11.7 pg/mL) and AA (364.1 +/- 153.5 pg/mL) but within normal range in patients with ET (each 20.0 and 22.1; NS, 22.1 +/- 8.2 pg/mL). In all subjects, the TPO concentrations in BM correlated well with the PB levels, and the former were consistently higher than the latter. The concentrations of TPO in BM also correlated with the levels of TPO mRNA in stromal cells. Furthermore, expression levels of TPO mRNA clearly correlated with megakaryocyte counts in NS and patients with ITP, indicating that stromal TPO actually enhances megakaryopoiesis. Thus, our results in the present study indicate that TPO from BM stromal cells is considered to play an essential role for megakaryopoiesis under various patho-physiological conditions.

Anemia, Aplastic↗
PubMed1998

A proof of glutathione S-transferase-pi-related multidrug resistance by transfer of antisense gene to cancer cells and sense gene to bone marrow stem cell.

In order to directly prove the involvement of GST-pi in drug resistance, it's antisense gene was transduced into human colorectal cancer cell line which has been shown to express high level of GST-pi and the sensitivity of this cell line to anticancer drugs were assessed. The transfectant showed higher sensitivity to adriamycin (3.3-fold), Cisplatnum (2.3-fold), Melphalan (2.2-fold), Etoposode (2.2-fold) than the parental cell, while the sensitivity to vincristine, mitomicin C, 5-fluorouracil was unchanged by transfection. When the transfectant and parental cells were innoculated in nude mice and treated with adriamycin, a significant suppression of tumor growth was observed with the transfectant as compared to the parental cell. On the basis of this observation, we then transduced sense GST-pi gene into human bone marrow stem cells (CD34+ cells) to protect them from toxicity of anticancer drug. The gene transduced CD34+ cells formed more CFU-GM than nontransduced CD34+ cell in the presence of adriamycin (30 ng/ml). Thus, the autotransplantation of GST-pi gene transduced cell into cancer patients to protect the bone marrow from subsequent highdose chemotherapy is considered to be a new strategy for cancer gene therapy.

Animals↗
PubMed1998

An apoptosis-inducing gene therapy for pancreatic cancer with a combination of 55-kDa tumor necrosis factor (TNF) receptor gene transfection and mutein TNF administration.

Intratumoral injection of recombinant human tumor necrosis factor (TNF) for inoperable pancreatic cancer has shown some efficacy in suppressing tumor growth or decreasing tumor markers. However, complete regression has not yet been achieved, possibly due to a lack of TNF receptors on tumor cells or an abundance of intracellular resistance factors. Recently, two distinct types of TNF receptors, R55 and R75, were identified, which are responsible for signaling of cytotoxicity and of proinflammation, respectively. In this study, a novel type of suicide gene therapy is proposed that is based on transfection of the R55 gene into human pancreatic cancer cells (AsPC-1 and PANC-1) and subsequent administration of TNF. The transfectants from both cell lines showed higher TNF susceptibility than their parental cells. In vivo tumor formation of an AsPC-1 clone (clone 10) inoculated in nude mice was substantially suppressed by administration of TNF. For practical use of this strategy, however, the adverse effects of TNF may become an obstacle. We previously produced mutein TNF 471, which had a higher affinity for R55, superior antitumor activity, and fewer adverse effects. This mutein TNF 471 manifested greater antitumor activity against clone 10. Because the R55 receptor is known to be involved in augmentation of cellular immunity by TNF, mutein TNF 471 is also expected to be highly potent in this function. In fact, the mutein TNF 471 induced higher splenic natural killer cell activity in nude mice inoculated with clone 10 than did native TNF. This property of augumenting cellular responses may be advantageous in the eradication of viable tumor cells left untransfected in practical gene therapy regimens in which 100% transfection of the R55 gene into tumors is not feasible. Thus, gene therapy combining transfection of the TNF-R55 gene with administration of mutein TNF 471 may provide a new modality for the treatment of pancreatic cancer.

Adenocarcinoma↗