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Biomedical subjects

T Tomoda

Publications and source records attributed to T Tomoda.

At least 19 recordsLinked to original sources
PubMed1995

Prevention of influenza by the intranasal administration of cold-recombinant, live-attenuated influenza virus vaccine: importance of interferon-gamma production and local IgA response.

To clarify which immunological factors were more effective in preventing influenza virus infection, we measured immunological parameters induced by vaccination and infection in vivo and in vitro. Healthy adult subjects (n = 128) were divided into vaccinated (n = 85) and untreated (n = 43) groups. Eighty-five were vaccinated intranasally with a trivalent cold-adapted recombinant influenza virus vaccine containing type A (H1N1 and H3N2) and B viruses. Subjects were mostly seropositive before vaccination. In 29 (80.6%) of the 36 examinees showing a prevaccination HI antibody titre of less than 1:128, the titre increased more than four times after vaccination. On the other hand, an increase of more than four times was found in four (8.2%) of the 49 individuals who had shown a prevaccination titre of more than 1:128. The IgA antibody was negligibly detected in the nasal wash specimens before vaccination, and was induced by vaccination in some cases. Lymphocyte proliferation and interleukin 2 (IL-2) production in cultured lymphocytes of the same subjects stimulated by H1N1 virus in vitro were correlated with the HI antibody titre. However, the interferon gamma (IFN-gamma) production was low before vaccination, regardless of the HI antibody titre, and showed a significant increase after vaccination. It was suggested that local IgA response and IFN-gamma production play important roles in the prevention of influenza. Since there was the outbreak of influenza A (H1N1) in Kochi Prefecture after completion of blood samples 6-8 weeks after the second vaccination, we examined the above hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1995

Beta-thalassemia with the IVS-I-1 (G-->T) mutation in a Japanese girl.

We analyzed the hemoglobins of a Japanese girl with beta-thalassemia and those of her immediate family. DNA sequencing of the cloned beta-globin gene from this patient revealed a point mutation at the IVS-I position 1 (G-->T). This rare point mutation has been found in Asian Indians, but this is the first reported Japanese case.

Base Sequence↗
PubMed1995

Interferon-alpha potentiates priming-dependent FMLP-induced neutrophil superoxide generation in a patient with chronic myeloid leukemia.

A 13 year old girl diagnosed as having chronic myeloid leukemia (CML) was treated with interferon-alpha (IFN-alpha) alone and 4 months later hematological remission was obtained. In the course of the IFN-alpha treatment there was neither infectious sign nor side effects. In this study we have examined the effect of IFN-alpha on superoxide O2- generation by polymorphonuclear neutrophils (PMN). The PMN of the patient generated less O2- than PMN from normal controls. When patient PMN were cultured in the presence of 1000 U/mL IFN-alpha, enhancement of the formyl-methionyl-leucyl-phenylalanine induced O2- generation following priming with tissue necrosis factor-alpha was observed. Over the course of the IFN-alpha therapy, such O2- generation was gradually restored. It is suggested that CML PMN are in the resting condition in terms of their ability to generate O2- and that IFN-alpha is effective in inducing O2- generation by CML PMN.

Adolescent↗
PubMed1995

Fetal valproate syndrome with reduction deformity of limb.

A case is reported of a female infant having multiple anomalies, including epicanthic folds, hypertelorism, bifid nasal bridge, shallow philtrum, low-set ears, brain atrophy, cleft palate, hemangioma on the chest, and reduction deformity of the left upper limb. This is the first case where an infant who was exposed to sodium valproate intra-uterine has a reduction deformity of the upper limb.

Abnormalities, Drug-Induced↗
PubMed1995

Marked increase of peripheral blood myeloblasts following G-CSF therapy in a patient with acute lymphoblastic leukemia.

A 9 year old boy with acute lymphoblastic leukemia (ALL) received recombinant human granulocyte colony-stimulating factor (rhG-CSF) and showed a marked increment of myeloblasts in the peripheral blood. He was administered repeated courses of intermediate-dose cytosine arabinoside (Ara-C) therapy (1500 mg/m2, days 1-5) for frequent central nervous system (CNS) relapse of ALL. The peripheral white blood cell nadir was less than 1000/microL, so he was treated with rhG-CSF. A marked increment of peripheral blood blasts was noted 3-5 days after rhG-CSF treatment. These cells decreased with the appearance of mature myeloid cells and disappeared about 2 weeks after the start of treatment. These findings suggested that the blasts might have the ability to differentiate into mature myeloid cells. A control patient with repeated CNS relapse of ALL showed no increment of peripheral blood blasts after similar repeated courses of Ara-C without rhG-CSF treatment. Cultured peripheral blood blasts obtained from the present patient showed differentiation into mature myeloid cells by morphological studies and surface marker analysis. These findings indicate that the peripheral blood blasts drawn by G-CSF were not leukemic blasts but normal myeloblasts.

Antigens, CD↗
PubMed1995

[Continuous infusion therapy with low dose cytosine arabinoside and etoposide in acute myelogenous leukemia patients hardly tolerable for intensive combination chemotherapy].

We evaluated the efficacy of continuous drip infusion therapy with low dose cytosine arabinoside (AraC) and etoposide (VP16) in poor-condition patients with acute myelogenous leukemia (AML). Patients' age ranged from 19 to 85 years with a median of 63 years. Principally they received continuous drip infusion for 14 days with AraC (20 mg/day) and VP16 (50 mg/day). Complete remission (CR) rate was 58.3% (7/12) in untreated cases, 33.3% (2/6) in refractory cases to the standard chemotherapy, and 28.6% (2/7) in relapsed cases. The duration of CR ranged from 1.5 to 20 (+) months (median 8) in untreated group and from 2 to 22 months (median 10) in refractory and relapsed groups. Adverse effects such as gastroenterological symptoms appeared but were tolerable. Although infections due to myelosuppression appeared in 22 of 25 cases, they were well controlled by antibiotics. Chemotherapy-related death was not observed. Although CR rate and CR duration of this therapy were not sufficiently high, the regimen was effective in some patients with refractory or relapsed AML. Further studies are required to establish the efficacy, indication and safety of this treatment.

Adolescent↗
PubMed1994

[Tubercle bacilli and the defence factors for infection in sputum and bronchoalveolar lavage fluid].

The defence factors against infection in sputum and bronchoalveolar lavage fluid (BALF) of patients with pulmonary tuberculosis were measured. As the defence factors, lactoferrin, lysozyme and secretory IgA (sIgA) in sputum or BALF of patients with bacilli (+) or (-) tuberculosis were measured and compared. Lactoferrin in sputum was significantly higher in patients with sputum smear positive tuberculosis compared with patients with smear and culture negative tuberculosis. SIgA in sputum was significantly higher in smear negative and culture positive cases compared with culture negative cases. As to the lysozyme in sputum, significant difference was not proved between each group. The level of these factors in BALF did not show significant difference between bacilli (+) and (-) cases. Neither significant correlation was observed among the level of three defence factors in sputum or BALF, nor between the number of leucocyte and tubercle bacilli in sputum. In tubercle bacilli positive group, however, significant positive correlation between the number of leucocyte and lactoferrin in sputum was found. In vitro experiments, high concentration of lactoferrin or lysozyme inhibited the growth of standard strain of tubercle bacilli (H37Rv) and BCG. The results suggest that the measurement of lactoferrin, lysozyme and sIgA in sputum or BALF is useful to determine the clinical activity of tuberculosis.

Bronchoalveolar Lavage Fluid↗
PubMed1992

Inhibition of interferon-gamma- and phorbol ester-induced HLA-DR and interleukin-1 production by the expression of a transfected poly(ADP-ribose) synthetase gene in human leukemia THP-1 cells.

We have examined a correlation between an expression level of poly(ADP-ribose) synthetase gene and the stage of monocytic differentiation. We selected three human leukemia cell lines, U937, THP-1, and J111, whose differentiation stage was characterized by nitroblue tetrazolium reduction activity, non-specific esterase activity, phagocytic activity and a cell surface marker. Enzyme activity and mRNA level of the synthetase decreased in accompaniment with the progress of monocytic differentiation. When THP-1 cells were treated with either interferon-gamma or phorbol ester, mRNA level of the synthetase decreased and HLA-DR or interleukin-1 was induced, respectively. We transfected expression plasmid of the exogenous synthetase gene to examine whether the down-regulation of the synthetase is a necessary step to induce these proteins. An expression of the exogenous synthetase gene inhibited the interferon-gamma- and phorbol ester-dependent induction of HLA-DR and interleukin-1. The results suggest that down-regulation of the synthetase may be a signal mediator of immunological response such as HLA-DR or interleukin-1 production in monocytes.

Cell Differentiation↗
PubMed1992

Experimental study on Reye's syndrome: inhibitory effect of interferon alfa on acetylsalicylate-induced injury to rat liver mitochondria.

Viral infection and acetylsalicylate (ASA)-induced mitochondrial aberration have been reported to play important roles in the pathogenesis of Reye's syndrome. We report that increasing amounts of ASA (0 to 250 mumol/L) resulted in increases in state 4 respiration and decreases in state 3 respiration in rat liver mitochondria in vitro when using alpha-ketoglutarate and/or beta-hydroxybutyrate as respiratory substrates, but not when using succinate as substrate. Interferon alfa (IFN-alpha) (1.5 to 5 x 10(4)IU/mL, approximately 1/100 the therapeutic dosage for humans) and interleukin-1 (IL-1) (1.5 to 2 x 10(4)IU/mL, nearly equivalent to the therapeutic dosage) decreased the severity of the above effects via interaction with mitochondrial membranes. Interferon gamma (IFN-gamma) and interleukin-2 (IL-2) had no such protective effect. Electron microscopic observation indicated that IFN-alpha prevented the induction of mitochondrial swelling by ASA. These results suggest that IFN-alpha may prove to be effective for the treatment of Reye's syndrome.

Animals↗
PubMed1992

The longevity of the immune response to filamentous hemagglutinin and pertussis toxin in patients with pertussis in a semiclosed community.

Titers of antibodies to the filamentous hemagglutinin (FHA) and pertussis toxin (PT) of Bordetella pertussis were studied in patients from a semiclosed community after an outbreak of the disease in 1985 and in the general population. In convalescent-phase serum obtained after B. pertussis infection in patients in the semiclosed community, high anti-FHA IgG and anti-PT IgG titers were observed; these titers tended to disappear over the next 5 years. On the other hand, among the medical staff, high anti-FHA and anti-PT IgG titers persisted during the same 5-year period. It seems likely that anti-FHA and anti-PT IgG levels reflect the frequency of exposure to the bacteria and that B. pertussis is widespread in the Japanese population. Although the anti-FHA IgG antibody response decreased in patients from the semiclosed community, the cellular immune response was maintained.

Adult↗
PubMed1992

[Laser photocoagulation for experimental choroidal neovascularization. 1. Mild dye laser photocoagulation].

The author treated experimentally produced choroidal neovascularization (ChNV) with mild dye laser photocoagulation (PHC). We treated these ChNVs with 590 nm wavelength, 200 microns spot size, 0.2 second duration and 50 mW of power. Eleven eyes of nine rhesus monkeys were used. Then these ChNVs were examined clinically and histopathologically at 24 hours, 2 weeks and a month after therapeutic PHC. Small ChNVs, less than 1/3 disc diameter healed successfully and histopathologically most of them were coagulated and disappeared. A few poorly developed ChNVs remained, but were well enveloped by the proliferating retinal pigment epithelial (RPE) cells. On the other hand, ChNVs of more than 1/3 disc diameter did not respond to weak PHC, grew actively over a month, and were not completely surrounded by proliferating RPE cells. These results suggest that by mild PHC, small ChNVs may be treatable, however, in large ChNVs, mild PHC may rather accelerate their activity.

Animals↗
PubMed1992

Stimulatory effect of interleukin-1 beta on the interferon-gamma-dependent HLA-DR production.

Expression of major histocompatibility complex (MHC) class II genes is induced by interferon-gamma (IFN-gamma) in antigen-presenting cells. When human leukaemia THP-1 and PL-21 cells were pretreated with phorbol ester, IFN-gamma-dependent induction of MHC class II gene was markedly enhanced. To elucidate the mechanism of the phenomenon, we examined the effect of cytokines which were secreted from THP-1 cells by the treatment of phorbol ester. Among those cytokines, interleukin-1 beta (IL-1 beta) had a positive effect on IFN-gamma-dependent induction of MHC class II genes. In order to rule out the possibility that different clones of THP-1 cells respond independently to IFN-gamma or phorbol ester, we showed that all independent single clones expressed MHC class II and produced IL-1 beta by IFN-gamma or phorbol ester, respectively.

Culture Media↗
PubMed1991

Fluctuation of gene expression for poly(ADP-ribose) synthetase during hemin-induced erythroid differentiation of human leukemia K562 cells and its reversion process.

We have studied the regulation of gene expression for poly(ADP-ribose) synthetase during erythroid differentiation and its reversion process. When human leukemia K562 cells were incubated in the presence of 80 microM hemin, benzidine-positive cells appeared at day 2 and 90% of the cells became positive at day 6. However, RNA blot analysis reveals that mRNA for gamma-globin was already abundant in untreated K562 cells and the level of the message was slightly increased by hemin-treatment. Spectroscopic analysis and polyacrylamide gel electrophoresis of the induced cell extracts indicate that hemoglobin molecules were not detected in untreated cells, and increased successively up to day 6. The hemin-induced cells were thoroughly washed, and then recultured in the absence of hemin. The benzidine-positive cells mostly disappeared 3 days after the elimination of the inducer. During the hemin-induced erythroid differentiation, the activity and mRNA for poly(ADP-ribose) synthetase decreased to 50% and 20% of the initial level at day 3 and a low level of the gene expression was maintained afterwards, whereas the activity and mRNA returned to the initial value 1 day after hemin elimination. The results indicate that the hemin-induced erythroid differentiation of K562 cells is a reversible process and depression of the synthetase may be involved in the progress of differentiation.

Blotting, Northern↗
PubMed1991

Enhanced expression of poly(ADP-ribose) synthetase gene in malignant lymphoma.

Over-expression of cellular protooncogenes has been proposed to function in the initiation and maintenance of malignancies. In order to distinguish malignant lymphoma from reactive proliferative diseases, we surveyed the expression levels of three protooncogenes(c-myc, c-fos and c-myb) in malignant lymphoma and reactive proliferative diseases. An increased level of c-myc or c-fos mRNA was observed in one case, respectively, out of three malignant lymphomata. The other cases exhibited no enhancement in protooncogenes. These oncogenes are critically regulated during differentiation, but the half-life of c-myc mRNA was very short, and the level of the mRNA decreased to the initial level very quickly. Thus, the high level of the expression of these oncogenes may not always be maintained in all malignant cells. We then examined the level of mRNA for poly(ADP-ribose) synthetase in those cases. An enhanced expression for the synthetase gene was observed in all five malignant lymphomata tested, but no increase in the level of the mRNA was observed in any reactive proliferative cases or normal lymph nodes. These results suggest that enhanced expression of poly(ADP-ribose) synthetase gene seems to be a common characteristic of protopathic malignant lymphoma. By using the characteristics of malignant lymphoma, the level of mRNA for the synthetase may be applicable for differential diagnosis of malignant lymphoma from several pathologically indistinguishable diseases.

Blotting, Northern↗
PubMed1991

Immune responses to Bordetella pertussis infection and vaccination.

To assess antibody and cellular immune responses, 156 healthy children were immunized at approximately 18 months of age with acellular diphtheria-tetanus-pertussis vaccine. Changes in antibody responses to filamentous hemagglutinin (FHA) and to pertussis toxin (PT) were similar in pattern, and antibody titers reached values equal to those from patients with convalescent-stage pertussis. The FHA-induced DNA synthesis in peripheral blood mononuclear cells was maximum at 4 weeks after the primary series, and these levels were equal to those of patients with pertussis. High amounts of PT-induced DNA synthesis were observed in both immunized and nonimmunized children; thus, PT seemed to act mainly as a nonspecific mitogen. Almost the same responses to several mitogens that activate different subsets of lymphocytes were observed in young infants compared with older children. Furthermore, young infants who had Bordetella pertussis infection responded by FHA stimulation almost as well as older children.

Age Factors↗
PubMed1991

Changes in Cu,Zn-superoxide dismutase gene during induced erythroid and myeloid differentiation.

We investigated the alteration of Cu,Zn-superoxide dismutase during erythroid and myeloid differentiation in order to elucidate its physiological significance in different types of cells. We measured enzyme activity and mRNA levels of superoxide dismutase in the process of differentiation to erythroid cells or myeloid cells. When human leukemia K562 cells are incubated in the presence of 80 microM hemin, benzidine-positive cells appear on day 1 and 80% of the cells become positive on day 5. During hemin-induced erythroid differentiation, Cu,Zn-superoxide dismutase activity increases 3.5-fold of the initial value and mRNA for Cu,Zn-superoxide dismutase increases prior to the activity to the same extent. On the other hand, when human promyelocytic leukemia HL-60 cells are incubated in the presence of 1.3% dimethyl sulfoxide, nitroblue tetrazolium-positive cells reach approximately 90% on day 5. During dimethyl sulfoxide-induced myeloid differentiation, the activity of Cu,Zn-superoxide dismutase decreases below 15% of the initial value on day 5 and mRNA for Cu,Zn-superoxide dismutase decreases as well. The results indicate that the synthesis of superoxide dismutase is linked with either the erythroid or myeloid differentiation program.

Blotting, Southern↗
PubMed1990

[Treatment and prognosis of retinoblastoma from 1975 to 1987].

Among 21 cases of retinoblastoma (28 eyes) treated during the past 14 years in our clinic, 14 cases were unilateral, and 7 were bilateral. The average ages at the first visit were 27 months in unilateral cases and 7.2 months in bilateral cases. In all unilateral cases, in all of which the tumors were large (over group III according to Reese's classification), we removed the affected eye, and all patients survived without any evidence of metastasis or recurrence during a 5-year follow-up period. In bilateral cases, we removed the advanced eyes in which the tumors were large (over group III according to Reese's classification) in all cases, and the contralateral eyes underwent conservative treatment by radiotherapy, photocoagulation or chemotherapy. When tumors in contralateral eyes were small (Group I or II in Reese's classification), tumors of the retina subsided and all patients survived without recurrence or metastasis. However, when the tumors were large (group V), tumors of retina did not subside and survival was very poor. Our results show that the prognosis for survival in bilateral cases depends mainly upon the size of the tumor in the remaining eye.

Child↗