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Biomedical subjects

S Ishizawa

Publications and source records attributed to S Ishizawa.

At least 19 recordsLinked to original sources
PubMed2003

High frequency of pro-B acute lymphoblastic leukemia in adults with secondary leukemia with 11q23 abnormalities.

To evaluate the frequency and cytogenetic and immunophenotypic features of therapy-related, precursor B-cell acute lymphoblastic leukemia (ALL), 152 cases of immature B-cell ALL were reviewed. These were compared to the frequency of therapy-related acute myeloid leukemia (t-AML) during the same time period. Eight ALL cases with a prior diagnosis of malignancy were identified, including six (4.0%) with prior therapy considered to be therapy-related ALL (t-ALL). The t-ALL cases followed treatment for breast carcinoma (two cases), lung carcinoma (two cases), lymphocyte predominance Hodgkin's disease and follicular lymphoma with a latency period of 13 months to 8 years. All t-ALL cases had a pro-B (CD10-negative) immunophenotype with significantly higher expression of CD15 and CD65, compared to the de novo CD10-positive ALL cases. All six t-ALL cases had MLL abnormalities by fluorescence in situ hybridization, and four showed t(4;11)(q21;q23). These represented half of all 11q23-positive adult ALL cases. During the same time period, 4.9% of all AML cases were considered t-AML. There was a 16.7% frequency of 11q23 abnormalities in the t-AML group. Despite the similar frequency in therapy-related disease among ALL and AML cases, there were differences in the frequency of the diseases and t-ALL represented 12% of all therapy-related leukemias. However, t-ALL represented 46% of all 11q23-positive therapy-related leukemias. The immunogenetic features of t-ALL appear distinct and may aid in identifying more cases of this disease type in the future.

Acute Disease↗
PubMed2001

Study on the role of G1 cyclins in Epstein-Barr virus-associated human lymphomas maintained in severe combined immune deficiency (SCID) mice.

Five Epstein-Barr virus (EBV)-positive human lymphoma cell lines maintained in severe combined immune deficiency (SCID) mice were used to investigate the role of G1 cyclins in EBV-induced lymphomagenesis. All the primary tumors had been negative for EBV but became positive after establishment in SCID mice, with monoclonal immunoglobulin gene rearrangement and EBV monoclonality. To compare the expression status of G1 cyclins, these EBV-associated lymphoma lines (6 EBV[-] human SCID mouse lymphoma lines, 13 human B cell lymphomas and 8 samples of human tonsil tissue) were examined by reverse transcription-polymerase chain reaction-Southern blotting, Western blotting and immunohistochemistry. mRNA expression of cyclin D1 (CCND1), cyclin D2 (CCND2), cyclin E (CCNE), cyclin-dependent kinase 2 (CDK2) and 4 (CDK4) was found in all 3 types of lymphomas. Western blotting demonstrated identical results. Immunohistochemistry revealed CCND1 to be negative in all lymphomas. CCND2 was positive and restricted to the nuclei in all EBV(+) SCID mouse lymphoma lines, whereas it was limited to the cytoplasm in half of the EBV(-) counterparts. CCNE was positive in the nuclei in all EBV(+) but negative in all EBV(-) SCID mouse lymphoma lines. Immunoprecipitation of EBV(+) and (-) SCID mouse lymphomas for CCND1, CCND2 and CCNE vs. p21, PCNA and CDK2 or CDK4 demonstrated that, in EBV(+) SCID lines, CCND2/CDK4 complexes were present without binding to p21, suggesting independence from p21 regulation. In EBV(-) SCID mouse lymphomas, half of the cases showed complex formation of CCND2/CDK4 without binding of p21. In contrast, CCND1/CDK4 and CCNE/CDK2 were under regulation of p21 in both EBV(+) and (-) lymphomas. These results suggest that differential expression of CCNDs, CCNE and CDKs, as well as variation in their subcellular localization and association with CDK-inhibitor protein, could explain differences in cell proliferation between EBV(+) and EBV(-) lymphomas.

Animals↗
PubMed2001

Non-Hodgkin's lymphoma of the ascending colon in a patient with becker muscular dystrophy: report of a case.

We herein present the findings of a 10-year-old boy with non-Hodgkin's lymphoma of the ascending colon which caused intussusception and intestinal bleeding. He had a history of Becker muscular dystrophy. However, he had neither hypertrophic calves nor cardiomyopathy, and his serum creatine kinase (CK) level always exceeded 2000 IU/l. Preoperatively, a laboratory examination revealed high serum levels of CK (2038IU/l), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), and the blood hemoglobin level was 7.0g/dl. A barium enema examination revealed an intussusception in his ascending colon, which was found to be a highly vascular tumor on Doppler ultrasound scans. A right hemicolectomy was performed. Macroscopically, the 5 x 6 x 8-cm solid tumor of the ascending colon resembled a submucosal tumor and had two ulcerous lesions at the tip. The tumor was histologically diagnosed to be a diffuse large B-cell lymphoma of the ascending colon. General examinations revealed no involvement of lymphoma postoperatively. At 13 months after surgery, the CK (37861U/l), AST (110lU/l), ALT (1381U/ l), and LDH (420lU/l) levels are still high, and the patient is doing well without any signs of recurrence.

Child↗
PubMed2001

[Systemic non-Hodgkin lymphoma initially presented with visual disturbance due to intrasellar lymphoma--a case report].

A case with systemic non-Hodgkin lymphoma involving the sella turcica and kidney is reported. A 69-year-old man presented with a progressive two month history of visual disturbance and headache. Neurological examination revealed bilateral visual disturbance and right optic atrophy. MRI showed a contrast-enhancing mass in the sella turcica. The tumor extended to the right optic nerve. Without extensive studies for systemic disease, the patient immediately underwent transsphenoidal surgery. The slightly firm, fibrous and vascular-rich tumor was subtotally removed. The histopathological examination revealed a malignant lymphoma, diffuse-large-cell type with B-cell phenotype. The postoperative course was uneventful and the patient's symptoms subsided gradually. The patient received radiation therapy and the tumor disappeared. Postoperative CT examinations of the abdomen and pelvis revealed a large mass at the upper portion of the left kidney. Ga-scan also suggested the mass to be consistent with the abdominal CT. However, the patient suddenly died of acute heart failure with unknown cause just before starting chemotherapy for systemic lymphoma. Patients presenting primary central nervous system lymphoma (PCNSL) may have systemic non-Hodgkin lymphoma. To exclude systemic non-Hodgkin lymphoma, systemic investigation is essential for the initial management of patients presenting PCNSL.

Aged↗
PubMed2000

Tumor regression by inductive hyperthermia combined with hepatic embolization using dextran magnetite-incorporated microspheres in rats.

We formulated a novel preparation of microspheres incorporating dextran magnetite complex (DM-MS), which enable magnetic field-induced heating for the induction of hyperthermia. Using a 500 kHz magnetic field combined with arteriolar embolization of DM-MS, inductive hyperthermia was performed for the treatment of liver tumors in rats. Three days after treatment, the percentage increase of tumor volume in the embolo-hyperthermia, embolization alone, and control groups were 28%, 124%, and 385%, respectively, with the embolo-hyperthermia group differing significantly from the remaining groups. This study demonstrated the feasibility of combining embolization of DM-MS with hyperthermia as an antitumor therapy.

Animals↗
PubMed1997

Primary adenocarcinoma in the urethrorectal fistula.

A 60-year-old Japanese man was hospitalized because of urinary leakage from the anus on October 3, 1994. Retrograde urethrography detected a fistula between the bulbous urethra and the rectum. Urethrocystoscopy revealed a tumor on the urethrorectal fistula. Tumor biopsy showed a well differentiated adenocarcinoma. Cystourethrectomy with fistulectomy, and ileal conduit urinary diversion were performed. Pathological examination revealed primary adenocarcinoma in the fistula with invasion to the prostatic urethra and bladder wall. The patient showed no evidence of a recurrence as of August, 1996.

Adenocarcinoma↗
PubMed1996

Malignant mesenchymoma arising from the prostate in Gardner's syndrome.

The first case of a primary malignant mesenchymoma arising from the prostate in Gardner's syndrome is reported. The neoplasm occurred in a 40-year-old man with a chief complaint of urinary retention. Biopsy findings were primary malignant mesenchymoma. Total cystectomy and lymphadenectomy were performed, but the patient died due to multiple metastases within 6 months. He had undergone a colectomy for polyposis coli 17 years earlier and had mandibular osteomas. This was the first case of malignant mesenchymoma arising from the prostate in Gardner's syndrome.

Abdominal Neoplasms↗
PubMed1994

Identification of a cis-acting element that is responsible for cadmium-mediated induction of the human heme oxygenase gene.

Heme oxygenase is an essential enzyme in heme catabolism and is inducible by various environmental derangements such as cadmium. The activity and mRNA levels of heme oxygenase were remarkably increased in HeLa cells by the treatment with cadmium. As a first step in studying the molecular mechanisms of this induction, we performed transient expression assays in four human cell lines including HeLa to analyze the cadmium-mediated inducibility of the fusion genes, containing the firefly luciferase gene as a reporter under the human heme oxygenase gene promoter. By determining the luciferase activity expressed in the transfected cells, we found the region between about 4.5 and 4 kilobase pairs upstream from the transcriptional initiation site of the heme oxygenase gene which confers cadmium-mediated inducibility on the fusion gene. The region was then subjected to further functional analysis in HeLa cells, which allowed us to localize the cadmium-responsive element to 20 base pairs. Gel mobility shift assays demonstrated that this 20-base pair element is specifically bound by nuclear protein(s) of HeLa cells, the binding activities of which were however unchanged by the treatment with cadmium. Using the synthetic cadmium-responsive elements containing various base changes, we have identified a 10-base pair sequence, TGCTAGATTT, required for the cadmium-mediated inducibility and in vitro protein binding. We thus suggest that this binding protein(s) is involved in the cadmium-mediated activation of the heme oxygenase gene. Incidentally, the consensus sequence of AP-1 binding site, TGAGTCA, is present downstream of this cadmium-responsive element. However, we provide evidence that AP-1 is not directly involved in the cadmium-mediated induction of the human heme oxygenase gene.

Animals↗
PubMed1994

Histological features of palatine tonsils in pustulosis palmaris et plantaris: a morphometric study.

The morphological expression of the immune response of palatine tonsils obtained from patients with pustulosis palmaris et plantaris (PPP) was investigated by morphometry in conjunction with immunohistochemistry. First, to differentiate the histological features of tonsils between PPP and habitual tonsillitis, each extent of the T cell dependent areas (T nodules), B cell dependent areas (lymph follicles), germinal centers, mixed areas of T cells and B cells, and lacunar epithelium was measured and compared on 38 patients with PPP and 47 with habitual tonsillitis, respectively. The most remarkable findings in PPP were enlargement of the secondary T nodules, and atrophy of the lymph follicles with a decrease in number of the germinal center cells and fibrosis. These changes of lymph follicles were similar to those in the older patients with habitual tonsillitis, which suggests the intensely advanced stage of the immune response within the tonsils. Second, the histological structures of the tonsils of 15 tonsillectomy effective cases (88.2%) was compared with those of two non-effective cases in curing skin lesions. The histological structure in the non-effective cases was very similar to that in habitual tonsillitis cases. This indicates that the histological findings may be useful in predicting the effects of tonsillectomy on PPP.

Adult↗
PubMed1994

[A case of small cell carcinoma of the stomach with multiple liver metastases].

We report a very rare case of small cell carcinoma of the stomach. A 69-year-old man, complaining of epigastric discomfort, was admitted to our hospital. Gastric endoscopy showed a Borrmann type 3 tumor at the lesser curvature of the cardia. Multiple liver metastases were observed in CT-scan, and total gastrectomy and cannulation to the hepatic artery were carried out. Macroscopically it was gastric cancer with P0H3N1T3M0, Stage IV b, histologically small cell carcinoma, intermed, INF gamma, ss, ly1, v3, n1(+), ow(-), aw(-). Immunochemotherapy was carried out, but liver metastases developed. The prognosis of this disease is very poor, resulting from rapidly developing metastases and invasion, in spite of treatments such as gastrectomy, chemotherapy and radiotherapy. More effective treatments are needed.

Aged↗
PubMed1993

Elevated complement activities of sera from patients with high density lipoprotein deficiency (Tangier disease): the presence of normal level of clusterin and the possible implication in the atherosclerosis.

Clusterin (apolipoprotein J, SP-40,40), as well as apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II), are apolipoprotein components of high density lipoprotein (HDL), but not of low density lipoprotein. In spite of the deficiencies of apo A-I, apo A-II and HDL in the sera of patients with Tangier disease, clusterin was found in them at normal level. While clusterin was present as the component of HDL with apo A-I in sera of normal donors, it was present as a protein which did not form a complex in sera of Tangier patients. SC5b-9 made from the sera of Tangier patients contained normal amounts of clusterin and was deficient in apo A-I, indicating that clusterin could be incorporated into the SC5b-9 complex without apo A-I. The complement activities of the sera of the patients were higher than those of normal donors. These results may be explained by the deficiencies of apo A-I, apo A-II and HDL in the patients, because they were suggested to be the inhibitors of the reactive haemolysis of complement. The elevated complement activities of the patients might be related to the severe atherosclerotic lesions in Tangier disease.

Adult↗
PubMed1993

Expanded primary T nodules in the palatine tonsils from patients with IgA nephropathy.

We designed a study to investigate the morphological expression of immune responses in the palatine tonsils from patients with IgA nephropathy. To distinguish between the histological characteristics of the tonsils in habitual tonsillitis (47 patients) and IgA nephropathy (11 patients), we studied the T nodules, B-lymphoid follicles, germinal centers, areas of mixed T and B lymphocytes, lacunar epithelium and connective tissues; then we compared patients with habitual tonsillitis and IgA nephropathy. The T nodules in patients with IgA nephropathy were enlarged, and this change was not accompanied by atrophy of B-lymphoid follicles. Morphologically, primary T nodules were predominant. In reactive lymph nodes, T nodules generally play an important role in the extra-follicular maturation of stimulated B lymphocytes into Ig-secreting plasma cells. Therefore the enlarged primary T nodules remind us that this maturation may occur more frequently in the tonsils of patients with IgA nephropathy than in those with habitual tonsillitis. This suggests that some immunoregulatory dysfunction exists in the secretory immune system of mucosa-associated lymphoid tissues in patients with IgA nephropathy.

Adult↗
PubMed1990

Interaction of upstream stimulatory factor with the human heme oxygenase gene promoter.

Upstream stimulatory factor (USF), originally identified in HeLa cells, interacts with the upstream promoter sequence of adenovirus 2 major late promoter (Ad2MLP) and activates its transcription. USF is present in uninfected HeLa cells and appears to be involved in the transcription of cellular genes related to stress. Recently, we have proposed that the rat heme oxygenase gene, newly identified heat-shock protein gene, is regulated at least in partly by a rat homolog of USF [Sato, M., Fukushi, Y., Ishizawa, S., Okinaga, S., Muller, R.M. & Shibahara, S. (1989) J. Biol. Chem. 264, 10251-10260]. We therefore confirm that the heme oxygenase gene is expressed in HeLa cells and its expression is increased by cadmium, suggesting that human heme oxygenase is a stress protein similar to the metallothioneins. Using partially purified USF from HeLa cells, we show that USF binds to the human heme oxygenase gene promoter and stimulates its cell-free transcription. The cis-acting element, identified as CACGTGACCCG, is located 34 bp upstream from the transcription initiation site, and contains the core sequence of the upstream promoter sequence of Ad2MLP. We propose that USF contributes to the transcription of the human heme oxygenase gene.

Adenoviridae↗
PubMed1990

[Prophylactic therapy for liver metastasis of gastrointestinal carcinomas using biological response modifiers (BRM): fundamental studies on the inhibition of experimental liver metastasis by intraportal administration of OK-432].

For prophylactic therapy to inhibit hepatic metastatic recurrence after surgical treatment of gastro-intestinal carcinomas, the effects of OK-432, a biological response modifier (BRM), were examined with inoculation of tumor cells and administration of OK-432 via portal vein. Experiments with the inhibition of liver metastasis were performed as follows. The animals were divided into five groups. Group 1: 1.0 KE of OK-432 was given intraportally 5 minutes after injection of 5.0 X 10(6) tumor cells per rat via the portal vein. Group 2: Non-medicated group, only 5.0 X 10(6) tumor cells per rat were injected into portal vein, as the control for group 1. Group 3: 0.5 KE of OK-432 and 2.5 X 10(6) tumor cells per rat were used. Group 4: 1.0 KE of OK-432 and 2.5 X 10(6) tumor cells were used. Group 5: Non-medicated group, injected with 2.5 X 10(6) tumor cells as the control group for groups 3 and 4. Colonies of metastases in the liver of each group were examined by autopsy on the 30th day after treatment. Metastases were observed in 75% of group 1, 100% of group 2, 58.8% of group 3, 64.3% of group 4 and in 90% of group 5. For the investigation of the mechanisms to inhibit these liver metastases, 51Cr labeled AH60C tumor cells were injected into the portal vein, and the remained of radioactivity in rat liver was examined. The result showed that OK-432 injected into the portal vein did not directly kill the lodging tumor cells. To prove the morphological evidence of inhibition of hepatic metastasis, the changes of tumor cells were microscopically observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Transcriptional control of the rat heme oxygenase gene by a nuclear protein that interacts with adenovirus 2 major late promoter.

Induction of rat heme oxygenase is mediated by at least two factors: its substrate heme and heat shock (Shibahara, S., Müller, R.M., and Taguchi, H. (1987) J. Biol. Chem. 262, 12889-12892). We have identified the cis-acting element of the rat heme oxygenase gene (HO gene), that was specifically bound by a nuclear protein prepared from rat glioma cells. We have termed this protein as heme oxygenase transcription factor (HOTF), whose estimated molecular weight is about 40,000. The element identified is CCACCACGTGACTCGAG (-51/-35) located just upstream of TATA-like sequence. The functional studies indicate that this sequence is required for the accurate and efficient initiation of transcription from the HO gene promoter. Since the HOTF-binding element is similar to the upstream promoter sequence (UPS) of the adenovirus 2 major late promoter (Ad2MLP), we examined whether rat HOTF is homologous to the upstream stimulatory factor (USF) or major late transcription factor previously identified in HeLa cells, which interacts with the UPS and activates the transcription from the Ad2MLP. HOTF specifically binds to the UPS of Ad2MLP, whereas HOTF failed to form a stable complex with the mutated HOTF-binding element lacking a GTGA sequence (-44/-42 of the HO gene), the sequence of which is identical to a core sequence of the USF-binding sites. Moreover, we show that like USF, HOTF is heat stable. These results suggest that HOTF may be homologous to USF or the major late transcription factor. Since USF is present in uninfected cells, it is conceivable that the expression of the HO gene is regulated at least in part by USF.

Adenoviruses, Human↗