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Biomedical subjects

M Tsuzuki

Publications and source records attributed to M Tsuzuki.

At least 73 records · Page 4Linked to original sources

[Intra-arterial chemotherapy with cisplatin, vincristine, methotrexate and adriamycin for recurrent penile cancer: a case report].

A 60-year-old man visited our hospital with a chief complaint of penile tumor on November 13, 1984. Circumcision of true phimosis was performed and biopsy of the 27 x 27 mm fixed tumor on the glans revealed well differentiated squamous cell carcinoma. Seventy Gy of electron irradiation to the penis revealed a complete response. On February 1, 1985 bilateral inguinal lymph node dissection was performed and revealed metastasis to a left inguinal node. In May 1990, erosive changes occurred on the irradiated region, and local recurrence was confirmed. Since 2 courses of MBD (methotrexate, bleomycin, cisplatin) chemotherapy was not effective, additional wedge dissection was performed. In January 1992, local recurrence was found. Four courses of intra-arterial chemotherapy (cisplatin, vincristine, methotrexate, adriamycin) was performed with a complete response. No evidence of disease has been recognized for more than two years after completion of the treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Donor buffy coat infusions for a patient with myelodysplastic syndrome who relapsed following allogeneic bone marrow transplantation.

A 49-year-old man with myelodysplastic syndrome (MDS, RAEB in T) who relapsed following allogeneic bone marrow transplantation (allo BMT) was treated with infusions of donor buffy coat leukocytes. He sustained hematologic and cytogenetic remission, but severe graft-versus-host disease (GVHD) developed for which cyclosporin A and prednisolone were required. This therapeutic approach appears to be valuable for relapsed MDS following allo BMT as well as for chronic myelogenous leukemia (CML).

Bone Marrow Transplantation↗

[Long-term selective beta 1-blockade therapy for a patient with anthracycline-induced cardiomyopathy].

A 44 year-old woman with acute myeloid leukemia (AML, FAB, M4E) developed heart failure during treatment with anthracyclines for AML. She had not experienced heart disease and her left ventricular ejection fraction (LVEF) was 59% at the end of a successful remission induction therapy. Because her LVEF decreased to 33% after early consolidation therapy, the chemotherapy for AML was discontinued. The cumulative dose of daunorubicin, aclarubicin and mitoxantrone was 486 mg/m2, 135 mg/m2 and 55 mg/m2, respectively. In October 1990, four months after the end of the chemotherapy, heart failure (class III, NYHA) developed and did not improve by treatment consisting of dobutamin, digoxin and diuretics. Anthracycline cardiomyopathy was histologically confirmed by endomyocardial biopsy. Then we administered selective beta 1-antagonist, metoprolol (Seloken), with an initial dose of 5 mg/day which was doubled 3 times every 4 or 8 weeks to 40 mg/day, according to the treatment schedule of dilated cardiomyopathy. She recuperated satisfactorily (Class I, NYHA), and was discharged on February '91. Her LVEF gradually improved and it has been maintained at above 50% on an outpatient basis. The patient has been in complete hematological remission during this period. It seems that low dose selective beta 1-antagonist therapy has a potential to improve myocardial function in some patients with anthracycline cardiomyopathy.

Aclarubicin↗

Gene activation by the Escherichia coli positive regulator, OmpR. Phosphorylation-independent mechanism of activation by an OmpR mutant.

In Escherichia coli, expression of the major outer membrane proteins, OmpC and OmpF, is regulated through the functions of OmpR and EnvZ at the transcriptional level in response to the medium osmolarity. OmpR is the crucial activator that helps RNA polymerase to efficiently trigger ompC and ompF transcription. This OmpR function is modulated by phosphorylation mediated by the cognate sensory kinase, EnvZ. Phosphorylation at the N-terminal domain of OmpR results in substantial enhancement of the DNA-binding ability of the C-terminal domain, thereby allowing the activation of ompC and ompF transcription by OmpR. Here we isolated an OmpR mutant which lacks the N-terminal half, but can enhance transcription in vivo. This novel type of OmpR mutant was revealed to have a single amino acid replacement of Gly227 to Cys. The newly-introduced-Cys residue allows OmpR molecules to form a stable dimer in vitro without the help of the N-terminal half. This altered C-terminal half is able to bind efficiently and specifically to the cognate DNA in vitro. It can function as an activator for ompC transcription in vitro in a phosphorylation-independent manner. These results suggest that the putative activator domain of OmpR, together with the DNA-binding domain, is most likely located in the C-terminal half. They also suggested that the phosphorylation of OmpR may not be essential for gene activation per se.

Bacterial Outer Membrane Proteins↗

Mechanism of gene activation by the Escherichia coli positive regulator, OmpR: a mutant defective in transcriptional activation.

The OmpR protein is an activator specific for the E. coli ompC and ompF genes. This protein functions in a phosphorylation-dependent manner through a presumed interaction with RNA polymerase. In this study we isolated OmpR mutants which were suggested to be defective for transcriptional activation, but not for DNA binding. Two such mutants, that we isolated, have a single amino acid alteration at positions 131 [P131S], and 179 [P179L], respectively, of OmpR, comprising 239 amino acids. These altered amino acids in OmpR may be implicated, directly or indirectly, in the presumed RNA polymerase/OmpR interaction that is important for transcriptional activation.

Bacterial Outer Membrane Proteins↗

Lysis of autologous tumor cells by large granular lymphocytes in patients with acute leukemia in complete remission: correlation between lytic activity and clinical outcome.

In order to evaluate the effect of specific immune response on prognosis in acute leukemia, we investigated the correlation between the lysis of autologous tumor cells (ATC) by lymphocytes and prognosis. Peripheral mononuclear cells (PMC) from most patients with acute leukemia in complete remission (CR) do not exhibit cytotoxic activity against fresh-frozen ATC, although they have adequate cytotoxic activity against K562 cells. When the large granular lymphocyte (LGL) fraction was used in this study, we observed lysis of ATC in 17 (43.6%) of 39 patients with acute leukemia (12 (42.9%) of the 28 patients with acute myelogenous leukemia (AML) and 5 (45.5%) of the 11 patients with acute lymphocytic leukemia (ALL)). With regard to prognosis, the lytic activity of the LGL fraction did not reflect the duration of CR. The median CR duration in AML patients was 13 months for the lysis-positive group and 11 months for the lysis-negative group. No significant correlation was also found between lytic activity of the LGL fraction and overall survival in each patient. However, the lysis-positive group tended to have a longer survival, the median overall survival being 48 months for the lysis-positive group vs 12 months for the lysis-negative group. The prolonging of overall survival in the lysis-positive group was attributed to a high rate of induction of second remissions in this group. Long-term patient survival in the two groups did not differ.

Adolescent↗

[Primary malignant lymphoma of the urinary bladder achieving complete response by COMPA intraarterial chemotherapy: a case report].

A case of primary malignant lymphoma of the bladder is reported. A 70-year-old woman was admitted to our clinic with the chief complaint of intermittent gross hematuria on March 31, 1992. Examination of cystoscopy, IVP, ultrasonography and CT scan suggested a non-papillary invasive bladder tumor. Pathological examination of transurethral biopsy revealed malignant lymphoma, B cell type. After 5 courses of intraarterial COMPA (CDDP, VCR, MTX, PEP, ADR) chemotherapy, she have been in complete remission. Intraarterial COMPA chemotherapy might be effective and useful for primary malignant lymphoma of the urinary bladder.

Aged↗

[Voiding dysfunction after abdominal radical hysterectomy. Comparison between patients with and without adjuvant irradiation therapy].

We evaluated 59 patients with voiding dysfunction after abdominal radical hysterectomy for uterine cancer. Of 59 patients, 45 underwent the surgery alone, and the other 14 underwent surgery and postoperative radiotherapy. Irradiation (mean dose, 60 Gy) was performed in bilateral commoni iliac regions excluding the bladder. In principle, the indwelling urethral catheter was removed 4 days after operation. All patients were followed up at the gynecological department until the onset of the voiding dysfunction. The mean interval between operation and the onset of voiding dysfunction was significantly longer (P < 0.01) in the group treated by surgery alone (7.9 years) than in the group treated by surgery in combination with radiotherapy (3.8 years). Voiding dysfunction developed earlier as the age at the time of operation was higher. No differences were observed in the volume of residual urine, the detrusor function, or the incidence of urinary tract infection between the two groups. These results suggest that aged patients develop voiding dysfunction earlier after radical hysterectomy than young patients, and postoperative radiotherapy shortens the interval between operation and the onset of postoperative voiding dysfunction.

Age Factors↗

[CAMBO-VIP for advanced diffuse large cell lymphoma (LSG classification)--a long-term follow-up study].

Twenty-two patients with advanced diffuse large cell lymphoma (LSG classification) were treated with the combination chemotherapy of cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide and prednisolone (CAMBO-VIP) from Oct. 1987 to Sept. 1989. Eighteen (90%) of 20 evaluable patients achieved complete remission and 2 patients had partial remission. With a median follow-up of 52 mos, 3 patients relapsed (17%), and 2 patients died. The actuarial overall survival and relapse-free survival at 4 years were estimated to be 90% and 83%, respectively. Myelosuppression was severe, but transient. No serious infection was seen, and no platelet transfusion was required. Oral mucositis and liver damage (Grade 3 in WHO grading) was seen in one patient each, but no treatment-related fatalities were observed. CAMBO-VIP is a well tolerated, effective treatment regimen for advanced diffuse large cell lymphoma.

Adolescent↗

[Increased blood cell destruction during vigorous regeneration of bone marrow after CAMBO-VIP chemotherapy for non-Hodgkin's lymphoma].

Alternating non-cross-resistant chemotherapy has been induced for the treatment of non-Hodgkin's lymphoma (NHL) with the aim of cure, even in advanced cases. We formulated a new high dose regimen, CAMBO-VIP, which was a weekly treatment. They were administered during alternate weeks for a total period of 12 weeks. We obtained high response rate and prolonged disease-free survival with this regimen. We noticed the elevation of serum LDH level in some patients at or shortly after the completion of CAMBO-VIP treatment. LDH elevation was not associated with liver function abnormality in terms of elevation of GOT or total bilirubin. All of these patients were in complete or partial response with no evidence of tumor progression. An LDH isozyme study which was done at the time of LDH elevation showed elevation of both LDH1 and LDH2. Interestingly serum haptoglobin was undetectable in all 6 patients measured at the time of LDH elevation. Reticulocytosis and leukoerythroblastosis in peripheral blood were also observed in all of these patients. These abnormalities including LDH elevation returned to normal within a rather short period, usually within 1 to 3 weeks. From these observations, it is most likely that these abnormalities were due to excessive blood cell destruction, which was observed in association with rapid recovery from myelosuppression.

Adolescent↗

[A case of completely responding stage D2 prostatic cancer with no evidence of disease 14 years after diagnosis].

A 58-year-old male complaining of pollakisuria, miction pain and back pain visited us Dec. 26, 1979. Rectal examination revealed the prostate enlarged by 5 digital width, stony hard and irregular. Transrectal needle biopsy revealed moderately differentiated adenocarcinoma of the prostate. Bladder neck invasion, pelvic and mediastinal lymph node metastases and multiple bone metastases were found. The case was diagnosed with prostatic adenocarcinoma T3N2M1 (OSS, LYM) stage D2. Three courses of chemotherapy using ifosfamide applied from Feb. 2, 1980 showed no marked effect except for partial pain relief. Hormonal treatment with diethylstilbestrol diphosphate was started from May 28 and arterial infusion chemotherapy using CDDP and 5-FU was performed 2 months later, resulting in size reduction of the prostate and pelvic lymph node metastases and disappearance of mediastinal lymph node metastases. Needle biopsy of the prostate was negative for cancer cells. After 8 months, Tegafur was started, and 12 months later radiotherapy was added to the prostate and pelvic lymph nodes. The abnormal accumulation in bone scan began to decrease after 14 months and achieved complete remission 28 months after the initial therapy. We discontinued the hormonal therapy 31 months later because of his complaint of chest discomfort and palpitation. At the present time, 14 years after the initial therapy, the prostate was 35 x 29 x 19 mm in size on transrectal ultrasonography with undetectable serum PSA level and no tumor cells but only mass fibrosis has been seen by pathological examinations. We considered this patient to be with no evidence of disease.

Adenocarcinoma↗

Mediastinal lymph node metastasis 38 months after surveillance for stage I seminoma: a case report.

We present a case report of a relapse to the mediastinal lymph node alone, 38 months after orchiectomy on surveillance for stage I typical seminoma. The patient, a 63-year-old man, was treated with high inguinal orchiectomy for left testicular tumor and close follow-up. After 38 months from the initial treatment, the chest X-ray film and CT scan revealed mediastinal tumor. Fine needle aspiration cytology performed under the bronchoscopy showed seminoma cells. Complete remission was achieved after three courses chemotherapy of cisplatin, vincristine, methotrexate, peplomycin and etoposide (COMPE). He has continued to be clinically disease-free 8 months after completion of the treatment. According to the available data in the literature, 94% of the recurrences was detected within 3 years after orchiectomy, and 92% involved retroperitoneal lymph node metastases. This is a rare case who had a late relapse in the mediastinum alone.

Humans↗

Expression of P-glycoprotein in de novo acute myelogenous leukemia at initial diagnosis: results of molecular and functional assays, and correlation with treatment outcome.

We investigated the expression of P-glycoprotein (P-gp) in 52 adults with de novo acute myelogenous leukemia (AML) at the initial diagnosis. We tested 52 patients by flow cytometry using the MRK16 monoclonal antibody (MoAb). To investigate the phenotype for multidrug resistance, 41 of the patients were analyzed using rhodamine 123 (Rh123). We found that 14 (27%) of the 52 patients were positive for P-gp expression by MRK16 MoAb using a cutoff of 5% positive cells. There was a significant correlation between the results of the two analyses (p < 0.01). We suggest that flow cytometry using MRK16 MoAb is acceptable for use in detecting P-gp expression in clinical samples. Among the 52 patients, 43 (83%) obtained a complete remission (CR) and 45% of remitters were predicted to be alive and in a CR after 8 years. Although the rate of CR on the MRK16-positive patients was comparable to that of the MRK16-negative patients, the MRK16-positive patients were prone to relapse. We conclude that determination of P-gp expression of de novo AML at initial presentation did not significantly influence the outcome of treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Severe rhabdomyolysis as a complication of peripheral blood stem cell transplantation.

We present a case of severe rhabdomyolysis developing after peripheral blood stem cell transplantation (PBSCT) in a 17-year-old woman with Ki-1 lymphoma. Severe muscle weakness, myoglobinemia and acute renal failure developed on day 23 following PBSCT associated with painful peripheral neuropathy. Cytomegalovirus infection may have been a contributory factor.

Acute Kidney Injury↗

An acquired Robertsonian 13;15 translocation in acute myelogenous leukemia (M5b).

A 43-year-old male developed acute myelogenous leukemia (AML, M5b) with an acquired Robertsonian 13;15 translocation. He did not achieve complete remission after sequential intensive induction chemotherapy and he died 13 months later. We reviewed 7 patients with this translocation reported in the literature. Acquired Robertsonian translocations are rare, but could represent an important event in the tumorigenesis of hematologic malignancies.

Adult↗

[Salvage chemotherapy for relapsed/refractory aggressive non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide and carboplatin].

Seventeen patients with refractory or relapsed, intermediate or high grade non-Hodgkin's lymphoma (NHL) were treated with the combination of dexamethasone (40 mg/body x 3d, iv) (DeVIC) between January and December 1992. The treatments were repeated every three weeks for a minimum of two courses unless the patient had PD. G-CSF (2 micrograms/kg, sc) was given during leukopenia in most cases. Of 16 evaluable patients 6 (38%) achieved a complete remission (CR) and 4 showed a partial remission. With median follow up of 15 (7-26) months (mos.) all CR patients were alive in CR, except for 1 patient who died of secondary AML. The actuarial 50% survival duration after DeVIC was 15+ mos. One patient died of sepsis but myelosuppression was generally moderate and no other serious toxicity was observed. Although this is a preliminary study, DeVIC regimen seems to be an effective salvage therapy for patients with refractory or relapsed NHL with acceptable toxicity.

Adolescent↗

[A study of toxicities and complications observed in alternating non-cross-resistant chemotherapy (CAMBO-VIP) for non-Hodgkin's lymphoma].

Thirty-nine patients with non-Hodgkin's lymphoma were treated with weekly alternating non-cross-resistant chemotherapy (CAMBO-VIP). We obtained a high response rate, and prolonged disease-free survival with side effects and complications of various severity were observed. Three patients were withdrawn from the study due to aggravation of liver cirrhosis, cerebral infarction, and poor tolerance. Thirty-six patients completed this 12-week intensive chemotherapy. The median treatment delay in all patients was 3 days (-4 to 29 days), and a delay of over 15 days was seen in 5 patients. The nadir of the neutrophil count was 0 to 2,100/microliters (median 140/microliters), and 15 patients were below 100/microliters. Two patients had pneumonia and 4 had herpes zoster infection. The platelet count nadir was 20,000 to 240,000/microliters (median 90,000/microliters). Ten patients were below 50,000/microliters, but none required platelet transfusion. Red cell transfusion was given in 6 patients. Elevation of transaminases was seen in 25 patients, but it was not serious except for a patient with liver cirrhosis. The elevation of serum LDH level and decrease of serum haptoglobin level seen shortly after completion of treatment seemed due to the increased blood cell destruction. Stomatitis was observed in 32 patients, 17 of whom showed more than grade 3 toxicity. Blister formation on palms and/or soles was noted in 6 patients. There was no treatment-related death observed.

Adolescent↗

[Rearrangements of immunoglobulin light chain and heavy chain constant region genes in B-cell malignancies].

We analyzed immunoglobulin (Ig) gene rearrangements in 69 patients with B-cell malignancies by Southern hybridization. We used 5 probes which covered JH 5'S mu and S gamma 3 loci of the Ig heavy (IgH) chain gene, and C kappa and kappa de loci of the Ig light (IgL) chain kappa gene, respectively. DNA rearrangements were observed in 68 out of the 69 patients using the JH probe. In 97% (33/34) of patients with non-Hodgkin's lymphoma (NHL), 100% (5/5) of chronic lymphocytic leukemia (CLL), 42% (10/24) of non-T cell acute lymphoblastic leukemia (non-T ALL), and in 0% (0/4) of chronic myelogenous leukemia lymphoid crisis (CML-LBC), the rearrangements were detected by C kappa and/or kappa de probes. Furthermore, the genotype of the light chain was defined by rearrangement patterns of these 2 probes. The by using the 5'S mu-probe, class switch recombinations were detected in 76% (25/33) of NHL, 20% (1/5) of CLL, 17% (4/24) of non-T ALL, and in 0% (0/4) of CML-LBC. Among them, 1 case of IgM NHL and 3 cases of double bearer NHL had rearranged on both IgH alleles by the constant region. The results of this study indicate that genotypes correspond well to phenotypes of B-cell malignancies and that the determination of genotype will be useful for making an exact diagnosis of B-cell malignancies.

DNA, Neoplasm↗