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Biomedical subjects

M Hirano

Publications and source records attributed to M Hirano.

At least 271 records · Page 15Linked to original sources

Expression of costimulatory molecules in human leukemias.

In order to determine the indication of B7 (B7-1 and B7-2) molecules-mediated immuno-gene therapy for human leukemias, we investigated 94 human leukemic samples for the expression of MHC molecules required for tumor antigen-specific signals and of B7-1, B7-2, and ICAM-1 molecules required for non-specific costimulatory signals. All samples were strongly positive for MHC class I and 84% for class II antigen. B7-1, B7-2 and ICAM-1 were expressed in 5%, 22% and 16% of the total cases, respectively. Especially in 54 AML samples, B7-1 was only expressed in one case, while B7-2 was detected in as many as 15 cases (28%). We have also examined 13 human myelo/monocytic cell lines for the expression of class II and costimulatory molecules and found that significant expression of costimulatory molecules was induced in human leukemic cells by some suitable drugs, among which interferon-gamma (IFN-gamma) was the most potent inducer. Our results indicate that when the B7-mediated immuno-gene therapy was applied to human leukemias, especially to AML, B7-1 was rather preferable to B7-2 in that the latter was more widely expressed on human leukemic cells. Furthermore, since gene-transfer systems occasionally accompany serious problems, it should be taken into account that costimulatory molecules on human myelo/monocytic leukemic cells could be induced ex vivo without the introduction of exogenous genes.

Antigens, CD↗

[Cardiac output in patients in their 90's].

Cardiac output was measured by the thermodilution method in nine patients aged 90 to 97 years. The patients were capable of walking in their daily lives before the injury or admission to the hospital, after which they were scheduled for operations. The causes for operations were localized and did not markedly influence general conditions of the patients. After heart rate, arterial blood pressure and mental condition of the patients had been stabilized, their cardiac outputs were determined before the induction of anesthesia. The results are as follows: Cardiac output: 3.58 +/- 0.90 l.min-1, cardiac index: 2.72 +/- 0.57 l.min-1.m-2. Previously published reports in Japan and the results of this study about the relationship between cardiac index and age suggest that as a whole there is a tendency for the cardiac index to decrease with aging.

Aged↗

[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↗

[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↗

Rapid progression of flat warts in a patient with malignant lymphoma after PBSCT.

A 51-year-old man with non-Hodgkin's lymphoma in his third remission received autologous PBSCT. He had had a couple of flat warts on his right hand since admission, which showed no progression during conventional dose chemotherapy. On day 15 of PBSCT, however, the warts began to develop and spread to his forehead, face, neck and arms over several days. The diagnosis of flat warts was made and human papilloma virus type 3 was detected by PCR analysis. Severe immunosuppression associated with PBSCT may have caused this rapid and disseminated growth of flat warts.

Hematopoietic Stem Cell Transplantation↗

[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↗

[Effective clinical use of cyclophosphamide in hematological malignancies].

Cyclophosphamide (CPA) is the most widely used alkylating agent in the treatment of hematological malignancies. We review current clinical potential of high-dose CPA administration in this field. The efficacy of dose intensification of CPA in CHOP regimen for patients with aggressive lymphoma is being investigated in some clinical trials. High-dose CPA administration and G-CSF infusion effectively mobilize high levels of peripheral blood stem cell suitable for autografting. High-dose regimens of CPA alone or in combination with other agents also have been used to treat various hematological malignancies in conjunction with stem cell transplantation (SCT). A variety of adverse effects have been observed with the high-dose CPA used in preparative regimens for SCT. Hemorrhagic cystitis and cardiac toxicity are common and dose-limiting toxic effect of high-dose CPA administration.

Antineoplastic Combined Chemotherapy Protocols↗

[Significance of 5'-deoxy-5-fluorouridine (5'-DFUR) administration before surgery for advanced gastric and colonic cancers--activity of pyrimidine nucleoside phosphorylase (PyNPase) and serum immunosuppressive acidic protein (IAP)].

We administered preoperatively 5'-deoxy-5-fluorouridine (5'-DFUR) for treatment of advanced gastric and colonic cancers, and measured pyrimidine nucleoside phosphorylase (PyNPase) in the excised tumor sample and serum immunosuppressive acidic protein (serum IAP), which is an index of the immunity of host-bearing cancer, while studying its direct antitumor effect and improved immunity. Patients with 24 advanced gastric cancers and 36 colonic cancers were randomly divided into a preoperatively administered group and a non-administered group. In the preoperatively administered group, 5'-DFUR (1,200 mg/day) was orally administered on preoperative days 7 approximately 14. After collecting samples (about 0.5 g) from adjacent normal tissues with tumor within 30 minutes after extirpation of tumor and freezing those less than -20 degrees C, the PyNPase level was measured as soon as possible. Moreever, serum IAP levels at pre-administration in the administered group and on admission in the non-administered group were measured. Those in the administered group were measured again on the operative day. No decreasing tendency of PyNPase was generally found in cases with gastric colonic cancers, and no significant difference in stage-II was not either. However, a decreasing tendency in tumor activity was found by pre-administration. Moreover, there was significant improvement in the serum IAP level in cases with gastric and colonic cancers by pre-operative administration of 5'-DFUR. This tendency was also found in advanced colonic cancer with Dukes-C by Dukes's classification. In conclusion, it was suggested that the pre-operative administration of 5'-DFUR for treatment of advanced gastric and colonic cancers has a favorable influence for prognosis because the tumor region was retarded by the high PyNPase activity according to the severity of tumors and elevating tendency of the immune response in host.

Administration, Oral↗

Reduced thyroidal uptake of inorganic iodine in liver cirrhosis.

Thyroid function was investigated in patients with liver cirrhosis. 123I uptake after four hours was significantly reduced in the liver cirrhosis group (n = 19) compared with the control group (n = 16) (2.6 +/- 0.3% vs. 5.0 +/- 0.6%, mean +/- SE, p < 0.01). There was no significant difference in the blood inorganic iodine level between the two groups, and the blood 123I count after ingestion of 123I capsules was not significantly different between the two groups. The area of the thyroid was slightly smaller in the cirrhosis group. A thyroid stimulating hormone (TSH) loading test showed no significant difference in the TSH value at any time point. The serum albumin level and prothrombin time were significantly associated with the 4-hour thyroidal 123I uptake (p < 0.01, p < 0.05, respectively). We show that the thyroidal inorganic iodine uptake was reduced in patients with liver cirrhosis and this reduction correlates with the severity of liver cirrhosis. Possible mechanisms include abnormal thyroid iodine transport capacity or reduced turnover of thyroid hormones resulting in a reduction in iodine uptake in liver cirrhosis.

Bilirubin↗

[A case of hemolysis induced by lansoprazole].

Hemolytic anemia and possible aplastic crisis with symptoms including jaundice, general fatigue and dark urine developed in a man being treated only by lansoprazole. Five days later, he was treated with antibiotics. The next day, he was admitted to our hospital because of jaundice. On admission, the hemoglobin was 14.0 g/dl, reticulocyte count 8/1000, platelets 79 x 10(9)/l and total bilirubin 12.4 mg/dl (indirect bilirubin 9.5 mg/dl). The above medications were discontinued. The direct Coombs antiglobulin test was positive. Examination of the complement revealed a C3 fiter at the upper limit of normal and an increased C4 and CH50. Three days after admission, he had a severe anemia. The hemoglobin was 3.3 g/DL. We thought it possible that aplastic crisis had followed the hemolytic anemia induced by lansoprazole. He was treated with blood transfusions and corticosteroids. He recovered from anemia within three weeks. Exhaustive studies to identify the cause of the hemolytic anemia were undertaken with negative results. We detected IgG antibody to lansoprazole. We believe that the hemolytic anemia was induced by lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Identification of a member of the TIS11 early response gene family at the insertion point of a DNA fragment containing a gene for the T-cell receptor beta chain in an acute T-cell leukemia.

In a previous paper (Proc. Natl. Acad. Sci. USA 84, 4264, 1987) we reported that a DNA fragment containing a gene for the T-cell receptor beta chain, which had been excised from chromosome 7q35 during D beta-J beta joining, was inserted into chromosome 6p21.3 in a patient with acute T-cell leukemia. We have since screened for genes in the vicinity of the insertion point and have identified a gene that is equivalent to the murine TIS11d gene, a member of TIS11 early response gene family, that contains unique Cysteine-Histidine motifs. The human TIS11d gene consists of two exons and encodes a polypeptide of 492 amino acids. The insertion of the DNA fragment observed in this patient is located at the carboxy-terminal portion of the TIS11d protein.

Amino Acid Sequence↗

Endothelin-1 evoked an increase and oscillations in cytosolic calcium concentration in adherent single human platelets and increased GMP-140 (P-selectin) in platelet suspension.

The effect of endothelin-1 (ET-1) on cytosolic calcium ion concentration ([Ca2+]i) in adherent single human blood platelet was determined by fluorescence digital imaging microscopy using Fura-2 as calcium probe. A dose dependent increase and oscillatory changes in [Ca2+]i in single platelets were evoked by ET-1 as with thrombin. Half and 1 microM of ET-1 increased (p < 0.01) the [Ca2+]i in single platelets from a resting level of 83 +/-3.4 nM to 120 +/- 13 nM and 240 +/- 20 nM respectively. The ET-1 induced increase in [Ca2+]i was suppressed by 1 mM EGTA, a calcium chelating agent in the medium. ET-1 increased the production of IP3 (quantitified by IP3 3H-radioreceptor assay kit) in platelets significantly (p < 0.05) in a dose dependent way. We measured the GMP-140 (P-selectin) level in the supernatant of human platelet suspensions incubated with thrombin and ET-1. Both thrombin and ET-1 increased the secretion of soluble GMP-140 in the supernatant of platelet suspensions. Therefore, we suggested that ET-1 increased [Ca2+]i in platelets by both calcium influx and IP3 mediated Ca2+ release resulting in activation and release of GMP-140.

Adult↗

Exon skipping caused by a base substitution at a splice site in the GTP cyclohydrolase I gene in a Japanese family with hereditary progressive dystonia dopa responsive dystonia.

We report a novel mutation at a splice site in the GTP cyclohydrolase I gene in a Japanese family with hereditary progressive dystonia with marked diurnal fluctuation (HPD)/dopa responsive dystonia (DRD). Reverse transcriptase-initiated PCR (RT-PCR) of lymphocyte mRNA showed both normal and small size fragments in the HPD patient and his asymptomatic mother. Sequence analysis revealed that skip splicing of exon 1 to exon 3 occurred in the small fragment. The patient and his mother were heterozygous for G --> C substitution at conserved consensus sequence GT at 5' end of the intron 2. Quantitative RT-PCR showed that the expression of normal GTP cyclohydrolase I mRNA decreased in their lymphocytes, while the HPD patient had more expression of mutant GTP cyclohydrolase I mRNA than his asymptomatic mother.

Adult↗