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Biomedical subjects

M Tsuzuki

Publications and source records attributed to M Tsuzuki.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cytokine therapy for hematological malignancies.

Recently various cytokines have been introduced into the clinic and have played important therapeutic roles in the treatment of hematological malignancies. Among these cytokines, we have focused on interferon (IFN) and granulocyte (G) or granulocyte-macrophage (GM) colony stimulating factor (CSF), which are currently the most useful cytokines in this review. IFN-a is one of most useful and wide-ranging antitumor agents in hematological malignancies. The most striking effects have been studies in chronic phase CML. Cytogenetic responses are seen in 30-40% of the treated patients, and a complete cytogenetic response can be seen in about 10%. Long-term survival can be expected in these patients. Considering the risk of graft-versus-host disease-associated mortality in allogeneic bone marrow transplantation, the most appropriate category of treatment is difficult to determine in IFN-responsive patients. Elucidation of the antitumor mechanism of IFN, as a prototype for other biological response modifiers, may revolutionize cancer treatment. G- and GM-CSF (CSFs) have reduced the duration of neutropenia, incidence of infectious episodes and days of hospitalization following cancer chemotherapy or stem cell transplantation. CSFs have also been used to mobilize peripheral blood stem cells and to increase the dose intensity of chemotherapeutic agents. Leukemic cells from many patients with acute myelogenous leukemia (AML) have surface receptors for CSFs and may proliferate in response to CSFs. However, several randomized studies showed that CSFs can be used safely and effectively in augmenting neutrophil recovery in patients with AML when given after induction chemotherapy. Various trials have been conducted to sensitize leukemic cells by CSFs, making them more susceptible to chemotherapy; but no convincing evidence has been obtained.

Antineoplastic Agents↗
PubMed1997

[Myelodysplastic syndrome with monosomy 7 following combination therapy with granulocyte colony-stimulating factor, cyclosporin A and danazole in an adult patient with severe aplastic anemia].

We report a case of severe aplastic anemia (SAA) treated with granulocyte colony-stimulating factor (G-CSF), cyclosporin A and danazole, in which myelodysplastic syndrome (MDS) with monosomy 7 developed eight months later. A 24-year-old woman was diagnosed as having SAA and was initially treated with G-CSF, cyclosporin A and danazole. At initial presentation, bone marrow aspirate revealed marked hypocellularity with a normal karyotype (46, XX [20]) and no MDS features. Eight months after initial treatment, leukocytosis and reticulocytosis were observed and bone marrow aspirate showed hypercellular marrow with morphological and cytogenetic features (45, XX, -7 [16]/46, XX [4]) characteristic of MDS (refractory anemia). A total of 75 mg (1.25 mg/kg) of G-CSF had been administered during the preceding eight months. Among seven previous reports published in Japan since 1992, in which MDS/acute myelogenous leukemia (AML) developed from SAA treated with G-CSF, six showed monosomy 7. Careful observation for leukemic transformation is therefore indicated in patients with SAA who are treated with G-CSF.

Adult↗
PubMed1996

Circadian expression of the carbonic anhydrase gene, Cah1, in Chlamydomonas reinhardtii.

We have investigated whether the expression of carbonic anhydrase genes (Cah1 and Cah2) is regulated by a circadian clock in Chlamydomonas. When cells were grown in ordinary air under 12 h light/12 h dark (LD) cycles, the levels of the Cah2 mRNA hardly altered during the cycles, while the Cah1 mRNA showed a strong diurnal rhythm. The rhythm of about 24 h continued at least 3 days even under continuous light. Temperature compensation of the rhythm was demonstrated, using cultures maintained at 16, 22, and 28 degrees C. These results indicate that the abundance of the Cah1 transcript is controlled by a circadian clock.

Animals↗
PubMed1996

[Five cases of hereditary high red cell membrane phosphatidylcholine hemolytic anemia in three families].

Five cases of hereditary high red cell membrane phosphatidylcholine hemolytic anemia in three families were described. All cases were clinically manifested by jaundice and splenomegaly. Hemolysis was evident from indirect hyperbilrubinemia, reticulocytosis and decrement of serum haptoglobin. Red blood cells showed morphological abnormalities such as poikylocytosis, anisocytosis and target cells on blood smears. Both direct and indirect Coombs' tests were negative. Ham test, sugar water test and hemoglobin electrophoresis showed no abnormalities. Osmotic fragility test showed decreased membrane fragility. Lipid analysis of red cell membrane showed increment of phosphatidylcholine content and decrement of sphingomyelin content, although plasma lipids were essentially normal. Influx and efflux of sodium through the red cell membrane were both increased. Splenectomy was performed without effect on one patient and the mother of other patients.

Adult↗
PubMed1996

[Treatment results for unselected patients with acute myelogenous leukemia. During a 10-year period, August 1984 to July 1994].

In order to analyse the clinical characteristics and outcome in acute myelogenous leukemia, 129 consecutive adult patients admitted to our hospital over a 10-year period, from August 1984 to July 1994, were studied. Their median age was 51 years, 17 (13.2%) of them had antecedent myelodysplastic syndrome (MDS) and 9 (7.0%) had secondary leukemia. Seventy-eight patients (60.5%) were considered eligible for cure-oriented intensive chemotherapy. Forty-four patients were ineligible of one or more of the following; age over 70, antecedent MDS or secondary leukemia. Additional 7 patients were excluded due to concurrent severe diseases. The median survival of the 129 patients was 441 days with an actuarial 5-year survival of 28.6 +/- 4.4%, and the disease-free survival (DFS) decreased with the increasing age of the patient. In 78 patients who were eligible for intensive chemotherapy, complete remission was achieved in 84.6% and overall DFS was 41.1 +/- 5.9% at 5 years, and their survival was longer than that of ineligible patients. It was suggested that considerable selection of patients, for example, due to old age, already existed before visiting our hospital. Analysis of clinical data of unselected patients might enable the development of a rational approach to the management of elderly patients.

Adolescent↗
PubMed1996

[Adult T-cell leukemia lymphoma primarily involving the epipharynx].

A 53-year-old woman was admitted to our hospital in April 1995, because of nasal obstruction, bloody rhinorrhea and hearing disturbance. She had no lymphadenopathy or skin eruptions. Laboratory examinations revealed a WBC count of 2.7 x 10(9)/L without abnormal cells, positive serum anti-HTLV-I antibody, normal lactate dehydrogenase and normal calcium level. MRI showed an epipharyngeal mass. No involvement was detected by CT scanning of the chest and abdomen, 67Ga scintigraphy and bone marrow biopsy. The pathological diagnosis of the biopsied specimen from the epipharyngeal mass was T-cell diffuse lymphoma, pleomorphic type. Monoclonal integration of HTLV-I proviral DNA was detected in lymphoma cells, which confirmed a diagnosis of extranodal adult T-cell leukemia lymphoma primarily involving the epipharynx. She was treated with CAMBO-VIP regimen followed by adjuvant involved-field radiotherapy and she continues to be in complete remission as of April 1996.

Female↗
PubMed1995

Impaired photosystem II in a mutant of Chlamydomonas reinhardtii defective in sulfoquinovosyl diacylglycerol.

The photosynthetic apparatus was characterized in a mutant of Chlamydomonas reinhardtii, hf-2, defective in the synthesis of a chloroplast-specific lipid, sulfoquinovosyl diacylglycerol (SQui-acyl2Gro). hf-2 showed reduced photosystem II (PSII) activity with little effect on photosystem I (PSI) activity, as compared with the parent. PAGE in the presence of dodecyl beta-D-maltoside (DodGlc2) of C. reinhardtii thylakoid membranes was used to isolate chlorophyll-protein complexes without chlorophyll (Chl) release in order to examine lipid species bound to these complexes. The four complexes obtained were shown to be the PSI complex, the PSII core complex and the two groups of the light-harvesting complex of PSII by analyses of 77-K emission spectra of Chl fluorescence and of subunit compositions. Lipid analysis of Chl-protein complexes in the parent revealed the localization of SQui-acyl2Gro in the PSII core complex and the two groups of the light-harvesting complex of PSII, but not in the PSI complex. These results suggest that SQui-acyl2Gro is responsible for PSII activity by associating with the core and light-harvesting complexes of PSII.

Animals↗
PubMed1995

Gene activation by the Escherichia coli positive regulator OmpR: a mutational study of the DNA-binding domain of OmpR.

The Escherichia coli DNA-binding protein, OmpR, is one of the best characterized of the bacterial positive regulators that enhance the transcriptional ability of RNA polymerase. OmpR, consisting of 239 amino acids, binds to specific sequences located upstream of the cognate ompC and ompF promoters. The C-terminal half of OmpR, consisting of about 120 amino acids, exhibits an inherent DNA-binding ability. To address the issue of DNA binding by OmpR, we selected a set of OmpR mutants, each of which has a single amino acid substitution in the C-terminal half of OmpR. In particular, we characterized a number of OmpR mutants which are defective in DNA binding and thereby result in an OmpF- OmpC phenotype. Among them, a putative positive control OmpR mutant was also obtained, which appears to be defective in phosphorylation-dependent transcriptional activation, but not in DNA binding. These results are discussed with general emphasis on DNA recognition by the E. coli family of OmpR-like regulatory proteins.

Amino Acid Sequence↗
PubMed1995

Isolation and characterization of mutants affected in lipid metabolism of Chlamydomonas reinhardtii.

Two mutants affected in lipid metabolism of Chlamydomonas reinhardtii were isolated by treating cells with ultraviolet light. Both mutants showed high chlorophyll fluorescent yields, as compared with parents, and were designated as hf-2 and hf-9 (for high fluorescence). hf-2 was shown to be defective in the synthesis of a chloroplast-specific lipid, sulfoquinovosyl diacylglycerol. hf-9 was shown to be defective in desaturation at the omega 6 position of fatty acids of monogalactosyl diacylglycerol, digalactosyl diacylglycerol, sulfoquinovosyl diacylglycerol and phosphatidylglycerol. The mutants exhibited alterations in photosynthetic activity and chloroplast ultrastructure.

Animals↗
PubMed1995

Interleukin-1 beta (IL-1 beta) and acute leukemia: in vitro proliferative response to IL-1 beta, IL-1 beta content of leukemic cells and treatment outcome.

We evaluated the in vitro proliferative response to exogenous IL-1 beta in terms of tritiated thymidine (3H-TdR) incorporation in leukemic cells obtained from 119 patients with various types of acute leukemia. The content of IL-1 beta in leukemic cells was measured by enzyme-amplified sensitivity immunoassay. We observed a significant proliferative response to exogenous IL-1 beta in leukemic cells from 27/66 patients with de novo AML, 1/29 patients with ALL, 2/3 patients with AUL, 8/12 patients with AML arising from MDS, 4/7 patients with myeloid crisis of CML, and 0/4 patients with lymphoid crisis of CML. Proliferation was marked in myeloid leukemic cells of a more premature stem cell origin. There were no significant differences in proliferative responses among the different FAB classes of de novo AML. The IL-1 beta content of leukemic cells was low in patients with lymphoid leukemia, but there was no significant difference among the various types of myeloid leukemia. There was no correlation between the proliferative response to exogenous IL-1 beta and the IL-1 beta content of leukemic cells. When we correlated the proliferative response to exogenous IL-1 beta with treatment outcome in patients with de novo AML, we found the rate of complete remission (CR) to be lower in those with a high proliferative response. We noted a longer duration of CR (p = 0.07) and of survival (p < 0.05) in patients with a low proliferative response. Thus, a high proliferative response to IL-1 beta in the cells of AML patients may indicate a poor prognosis.

Acute Disease↗
PubMed1995

Early-onset respiratory syncytial virus pneumonia after allogeneic bone marrow transplantation.

A 41-year-old woman with follicular lymphoma developed sporadic respiratory syncytial virus (RSV) pneumonia shortly after allogeneic bone marrow transplantation from an HLA-matched sibling. RSV pneumonia is potentially fatal in immunosuppressed patients, but she improved along with the recovery of bone marrow function without specific treatment. Early recovery of myelosuppression supported by granulocyte colony-stimulating factor may have helped to control RSV pneumonia.

Adult↗
PubMed1995

Phosphotransfer circuitry of the putative multi-signal transducer, ArcB, of Escherichia coli: in vitro studies with mutants.

Recently we demonstrated the occurrence of a novel device of signal transducers in Escherichia coli. This class of bacterial sensory kinases, typified by ArcB and BarA, possesses two phospho-donor (His) sites, together with a phospho-accepting (Asp) site. These multi-phosphorylation sites were suggested to make a phosphotransfer circuit. To clarify this complex circuitry, we carried out a series of in vitro assays involving a set of ArcB mutant proteins which have an amino acid substitution at each putative phosphorylation site (His-292, Asp-576 and His-717). By these in vitro phosphorylation and/or phosphotransfer assays, the followings were assessed: (i) ArcB autophosphorylation; (ii) ArcB-mediated phosphorylation of the cognate response regulator, ArcA; (iii) ArcB-mediated phosphorylation of its truncated form (ArcBc) encompassing only the C-terminal phosphorylation site (His-717); (iv) phosphotransfer from ArcBc to ArcA; and (v) phosphotransfer from ArcBc to ArcB. On the basis of these in vitro results, a complex circuitry was revealed for the signal transducer ArcB. This evidence obtained in vitro supports the view that ArcB can serve as a powerful device for not only propagating multi-signals, but also making up signalling networks, in ways more sophisticated than previously thought.

Bacterial Outer Membrane Proteins↗
PubMed1995

A case of mitral regurgitation whose nocturnal periodic breathing was improved after mitral valve replacement.

Nocturnal periodic breathing (PB) is often observed in patients with congestive heart failure (CHF). We investigated the sleep architecture polysomnographically in a 54-year-old man with CHF due to mitral regurgitation before and after surgical treatment. We found that the overnight frequency of central dominant sleep apnea decreased from 154 to 56, and the lowest nocturnal oxygen saturation increased from 66% to 85% postoperatively. These improvements in the manifestations of PB might be attributed to the improved hemodynamics after successful valve replacement.

Cheyne-Stokes Respiration↗
PubMed1995

[Clinical results of IV-compa (cisplatin, vincristine, methotrexate, peplomycin and adriamycin) chemotherapy for advanced urothelial cancer].

We have developed a new combination intravenous chemotherapy regimen called COMPA (IV-COMPA). The clinical value of IV-COMPA chemotherapy was evaluated based on the results of 24 patients with urothelial cancers. From October 1989 through October 1993, a total of 24 patients (20 males and 4 females) received IV-COMPA chemotherapy at Tokyo Medical College Hospital and Tokyo Medical College Hachioji Medical Center. All patients had advanced transitional cell carcinoma or adenocarcinoma of the urothelial tract (renal pelvis, ureter or bladder). One course of IV-COMPA was delivered at 2-week intervals and consisted of 30 mg/m2 CDDP on day 4 and 5, 0.6 mg/m2 VCR (Oncovin) on day 1 and 2, 5 mg/m2 MTX on day 2 and 3, 5 mg/m2 PEP on day 1, 2 and 3, 20 mg/m2 ADM on day 4. A few patients received the same regimen without peplomycin called IV-COMA to avoid pulmonary fibrosis. Fifteen patients with surgically confirmed invasive carcinoma were defined by at least 1 of the following criteria: multiple tumors or size greater than 5 cm, grade 3, stage P3 or P4, pN+, pR1, pL1, pV1, or secondary carcinoma in situ. These patients were treated with 2 or 3 corpses of postoperative IV-COMPA chemotherapy to improve prognosis. In this group, 14 of 15 (93%) are alive at a median follow-up of 22 months (range, 8-57 months) and actuarial survival rates of 1 and 3 years were 100%, 90.9%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

[Clinical study of renal cell carcinoma with brain metastasis].

Of 130 cases with renal cell carcinoma treated at Cancer Institute Hospital from January, 1981 to December, 1992, 14 (10.6%) developed brain metastasis, 12 of whom had had preceding pulmonary metastasis. Interval between the initial treatment of the primary lesion (nephrectomy in 13, embolization in 1) and the diagnosis of brain metastasis ranged 0 to 57 months with a median of 11 months. Twelve patients had clinical symptoms such as headache, vomiting, paralysis or disturbance of consciousness. Eleven patients were treated with external beam irradiation (30-60 Gy linear accelerator). Only 3 (30%) of 10 patients with measurable lesion on CT scan achieved PR but 6 (66.7%) of 9 had symptomatic improvement. Especially, chronic intracranial hypertension such as headache and vomiting disappeared in 5 (83.3%) of 6. Average survival period and one year survival after the diagnosis of brain metastasis were 5 months and 14.3%. Although most of the patients with brain metastasis died of the progression of other organ metastasis, radiation therapy for brain metastasis was useful to palliate the agonizing symptoms.

Adult↗
PubMed1995

[Bilateral renal cell carcinoma of von Hippel-Lindau disease associated with von Willebrand disease: a case report].

A 42-year-old man diagnosed with von Willebrand disease 7 years earlier visited his home doctor with a chief complaint of gross hematuria. Abdominal ultrasonography showed bilateral renal tumors. He was referred to our hospital on June 15, 1993. His mother also had von Hippel-Lindau disease and was treated by hemodialysis after bilateral nephrectomy. The examination and imaging revealed bilateral renal cell carcinoma of von Hippel-Lindau disease associated with von Willebrand disease. Partial nephrectomy and enucleation for a small tumor on the right side and enucleations for five tumors on the left side were performed. Histological diagnosis of all tumors were renal cell carcinoma, clear cell subtype, grade 1 approximately 2. The patient has been well without local recurrence or distant metastasis for 16 months since the operation. This is the first case of bilateral renal cell carcinoma of von Hippel-Lindau disease associated with von Willebrand disease in Japan.

Adult↗