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Biomedical subjects

S Taniguchi

Publications and source records attributed to S Taniguchi.

At least 505 records · Page 28Linked to original sources

Treatment of myelodysplastic syndrome and atypical leukemia with low-dose aclarubicin.

To study the therapeutic effect of low-dose aclarubicin (ACR), we carried out comparative treatment of 15 patients with myelodysplastic syndrome (MDS) and atypical leukemia using this drug. Complete remission (CR) was achieved in three patients with RAEB-t and one patient with AML, partial remission was obtained in one patient with RAEB and hematological improvement in one patient with refractory anemia (RA). Interestingly, prolonged CR for more than 26 months with persistent chromosomal abnormalities was observed in a case of AML, which progressed from RA. Myelosuppression caused by low-dose ACR was milder than that caused by low-dose Ara-C. Furthermore, in vitro studies indicated that ACR induced differentiation of bone marrow cells from one patient with MDS. From these observations, it is suggested that low-dose ACR may be an alternative to low-dose Ara-C for treatment of MDS, and that the in vivo effect of ACR may be mediated by the differentiation of abnormal hemopoietic clones.

Aclarubicin↗

Distribution of IL-3 activity in mice transplanted with IL-3 producing T cells (STIL-3): abrogation of the distribution of STIL-3 cells into the liver and liver hemopoiesis by splenectomy.

Distribution of IL-3 producing T cells, STIL-3, in splenectomized mice after intravenous injection was studied in order to determine the site of IL-3 production in the splenectomized mice. Hematological features of STIL-3-inoculated mice after splenectomy were also studied. Splenectomy prior to inoculation of STIL-3 cells resulted in a slight increase in the level of IL-3 activity in most lymphohemopoietic tissues, but resulted in a slight decrease in the level of IL-3 activity in the plasma. The splenectomy also abrogated granulocytosis which was evident in sham-operated host mice. Hepatomegaly and a number of granulocytic foci in the liver were observed in STIL-3 inoculated mice, but this was again abrogated completely by the splenectomy. These results suggest that the spleen is the major site of granulopoiesis in response to the stimulus with IL-3, and also that the spleen is essential for the migration or metastasis of STIL-3 cells to the liver.

Animals↗

Expression of the fos oncogene in B16 melanoma cells exhibiting different metastatic abilities.

Expression of the c-fos oncogene in B16 melanoma with high and low metastatic abilities was investigated. In Northern blot analysis, a highly metastatic B16-F10 melanoma cell line showed a higher extent of transcription of the fos gene than did a low metastatic B16-F1 cell line. Immunohistochemical studies revealed that B16-F10 cells stained more strongly than B16-F1 cells, both in vitro and in vivo, using the antibody against fos proteins. These results suggest that fos product may be involved in the regulation of gene expressions related to metastasis of B16 melanoma.

Animals↗

Serotonin metabolism in the arthus reaction.

To better characterize the role of serotonin in the Arthus reaction, we examined the concentration of the amine and the activities of serotonin-metabolizing enzymes, monoamine oxidase (MAO) and serotonin-N-acetyltransferase (NAT), in reaction sites induced in guinea pig skin. The specific activity of total MAO in the intact skin was 108.0 +/- 15.9 pmol/min/mg protein, and consisted of about 92% of type A activity and 8% of type B. The activity of total MAO was about 10 times greater than that of NAT. Total MAO activity increased to 130%-150% of control levels at 2 h after initiation of the reaction and approximated the control level at 3 to 6 h. Subsequently, the activity decreased linearly to 50% at 12 h and to 20% at 24 h. Although the time-dependent changes of MAO type A activity were similar to those of total MAO activity, MAO type B activity increased to 42% at 30 min, remained at 30%-40% until 6 h, and then decreased to 20% at 12 h and to 5% at 24 h. NAT activity in the reaction sites decreased with time to 50% of the control at 30 min and to 35% at 4 h and was stationary until 24 h. The serotonin concentration decreased linearly with time to 16% of the control level at 1 h, increased sharply to 240% at 6 h, and remained at more than 200% until 24 h. This biphasic change in serotonin concentration seems to be related to the dynamic changes in the activities of serotonin-degrading enzymes. In addition, the accumulation of platelets in the reaction sites may increase serotonin concentration and MAO activity subsequent to 1 h after the initiation.

Animals↗

Correlation of contractility and proliferative potential with the extent of differentiation in mouse fibroblastic cell lines cultured in collagen lattices.

Four types of fibroblastic cell lines at various stage of differentiation, which had been derived from syngeneic mice, were cultured in collagen lattices (reconstituted dermis model). Lattice contraction, growth in the lattice, and cell morphology were compared. The following cell lines were used: [I] precrisis cells within several subcultures derived from the skin of Balb/c mice, [II] an established normal cell line derived from syngeneic mice (Balb/3T3 clone A31), and [III] two transformed lines (Balb/3T12-3, 3T3-B-SV40) originating from [II]. The cells adopted a bipolar spindle form in the collagen lattice. Lattice contraction was the most marked with cell type [I] followed in order by [II] and [III]. Relative growth in the lattice occurred in the reverse order (III greater than II greater than I). These findings suggested a correlation between lattice contraction and growth in the lattice and also between the extent of differentiation and lattice contraction.

Animals↗

Effects of human recombinant tumor necrosis factor-alpha (TNF-alpha) on the proliferative potential of human keratinocytes cultured in serum-free medium.

The effects of human recombinant tumor necrosis factor-alpha (TNF-alpha) on human keratinocytes cultured in a serum-free medium were investigated. TNF-alpha markedly suppressed cell growth. The growth-inhibitory effect was reversible and cytostatic at a concentration of 1-5 U/ml, but appeared to be irreversible and cytocidal at 10 U/ml. The growth suppressive effect was more marked when TNF-alpha was added in the late growth phase or preconfluent phase than when it was added in early or mid-growth phases. No effects of TNF-alpha on cell adhesion to the substrate were observed. These results indicate that TNF-alpha is a very potent anti-proliferative agent for human keratinocytes.

Cell Adhesion↗

Infiltration of melanoma cells into the type I collagen gel.

Melanoma cells were cultured on type I collagen gel, and the infiltration of of those cells into the gel was observed. B16 murine melanoma cells initially adopted a spherical form on the gel, but they assumed a dendritic form after infiltration into the interior. The degree of infiltration increased very rapidly and was time-dependent. No correlations between the growth rate or melanogenic activity and infiltrative potential were observed. When Syrian hamster and human melanoma cell lines were cultured, the degrees of infiltration varied. This culture system using collagen gel is considered to be a useful in vitro model of tumor cell invasion.

Animals↗

Development of postpartum spontaneously resolving transient Graves' hyperthyroidism followed immediately by transient hypothyroidism.

A 25-year-old woman with a history of Graves' disease, in remission for 8.5 years following 6 months of methimazole therapy, first came to our attention 5 months after her first delivery with clinical and biochemical hypothyroidism, markedly elevated titre of anti-thyroid microsomal antibody (MCHA; 1:102400) and mildly elevated activity of thyrotropin-binding inhibitory immunoglobulins (TBII; 29.5%). After short-term (3 months) treatment with L-thyroxine therapy, the development of hyperthyroidism in the first trimester of the second pregnancy, which remitted through the second and third trimesters, was observed. TBII showed a peak value (93.1%) 1 month after the onset of hyperthyroidism, and a normal value (12.4%) 6 d after delivery. One month after the second delivery, the patient developed hyperthyroidism, with an elevation of 99mTc thyroid uptake (5.58%; normal range 0.5-2.5%), which was immediately followed by transient clinical and biochemical hypothyroidism. Concomitant increases in MCHA titre and TBII activity were observed after delivery, and both reached peak levels (1:409600 and 81.0%, respectively) one and a half months after the onset of hypothyroidism. Thyroid-stimulating antibody (TSAb), measured using FRTL-5 thyroid cells, was detected at a weakly positive level (161%) on initial examination, and the serial change in TSAb was almost identical to that in TBII. Patients with Graves' disease may develop Graves' type hyperthyroidism, followed immediately by transient hypothyroidism due to coexisting destructive autoimmune thyroiditis during the early postpartum period, despite increasing TSAb activity.

Adult↗

Immunohistochemical and ultrastructural localization of epidermal growth factor receptor in human liver and hepatocellular carcinoma tissues.

Expression of epidermal growth factor receptor (EGF-R) in human hepatocellular carcinoma (HCC), hepatoblastoma and non-cancerous liver tissues was investigated immunohistochemically in order to evaluate the possible role of EGF-R expression in neoplastic transformation of hepatocytes. Immunoreactive EGF-R molecules were identified on frozen sections by means of the avidin-biotin immunoperoxidase complex technique using a monoclonal antibody recognizing an epitope of the external domain of human EGF-R. Linear positive staining was present on the surface of carcinoma cells in one hepatoblastoma and in 9 of 11 HCCs. In addition, an enhanced level of surface EGF-R expression was observed on the tumor cells in 9 of 12 cases in comparison with that on hepatocytes in surrounding non-cancerous liver tissue, which in most cases showed chronic inflammation, hepatocyte injury or regeneration. No positive staining in the form of coalescent cytoplasmic granules was present in HCC or hepatoblastoma cells, nor in the cytoplasm of hepatocytes in normal or non-cancerous diseased liver tissue. Little or no reactivity was present on the surface membrane of hepatocytes in the normal liver tissues of 8 control cases. Furthermore, immunoelectron microscopy revealed the localization of this immunoreactive EGF-R molecule on the plasma membrane. Considering that the functional form of EGF-R could be localized on the plasma membrane, the enhanced expression of immunoreactive EGF-R on the tumor cell surface demonstrated here may suggest a possible role of EGF-R in the development or progression of human HCC as well as in hepatocyte regeneration.

Carcinoma, Hepatocellular↗

Effect of N-methionine-free, bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in a primate model.

We demonstrate the in vivo effects of bacterially synthesized, N-methionine-free recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) using a crab-eating monkey model. Monkeys were treated with cyclophosphamide (60 mg/kg) and administered with rh GM-CSF (30 micrograms/kg/d) subcutaneously (s.c.) for 7 days. Within 12 h, a transient increase of neutrophils (greater than 15.0 x 10(9)/l) was observed, and complete recovery of WBC counts was obtained by d 9 (d 16 in control monkeys). Neutrophils and eosinophils were absolutely increased (greater than 8 x 10(9)/l) on d 10. Readministration of rh GM-CSF (30 micrograms/kg/d, s.c.) for 3 d (including control monkeys) revealed absolute increases of neutrophils, eosinophils, monocytes and platelets. A two-fold increase of granulocyte/macrophage colony-forming units was also seen in the bone marrow, while the number of burst-forming units-erythroid was not affected. These data indicate that rh GM-CSF of this type stimulates granulopoiesis and thrombopoiesis in vivo.

Animals↗

Acute leukemia during pregnancy. Association with immune-mediated thrombocytopenia in mother and infant.

A 29-year-old female in the 20th week of pregnancy was admitted because of a change in the ABO blood group and bleeding tendency. Acute myelogenous leukemia was diagnosed with a weak reaction of red blood cells with anti-A antibody and a decreased level of A-transferase activity. Though the patient tolerated intensive chemotherapy and achieved complete remission, thrombocytopenia persisted after consolidation chemotherapy. Since platelet-associated IgG was elevated, thrombocytopenia was considered to be immune-mediated. In the third trimester, premature separation of the normally implanted placenta developed and cesarean section was performed. The male baby was also thrombocytopenic, but successfully treated with gamma-globulin.

Abruptio Placentae↗

PUVA increases ornithine decarboxylase gene expression in mouse skin.

The influence of topical PUVA on the activity of ornithine decarboxylase (ODC) and its gene expression was investigated in the skin of hairless mouse. After 1 h of application of 0.3% 8-methoxypsoralen, irradiation of 3 J/cm2 of ultraviolet A (UV-A) was administered. The ODC activity markedly increased and peaked at 24 h following UV-A irradiation. The ODC mRNA level, analyzed in dot-blot analysis, elevated to about 5 times that of control at 24 h after treatment. These results show that the PUVA-induced ODC activity is due in part to an increase in ODC gene expression.

Animals↗

Distribution of gamma-glutamyl transpeptidase in human pancreas: immunohistochemical study with a monoclonal antibody.

We studied in detail the distribution pattern of gamma-glutamyl transpeptidase (gamma-GT) in human pancreas, using the immunoperoxidase technique and a monoclonal antibody to human kidney gamma-GT. Positive reaction was confined exclusively to the luminal surface of the centroacinar cells and the epithelia of the intercalated, intralobular, and interlobular ducts. The immunoreaction was stronger in the intercalated and intralobular ducts than in the interlobular ducts. The acinar cells did not show any reaction. The islets of Langerhans were heavily surrounded by the ducts, and normal islet cells showed no reaction. The course of the ducts, from the acinar lumina to the interlobular ducts, was delineated by using reaction sites positive for gamma-GT as markers. The courses of the ducts, which comprise the pathway for pancreatic juice, were found to vary widely in their connections with each other, especially between the intralobular and interlobular ducts. At least three separate routes could be identified.

Antibodies, Monoclonal↗

The mechanism involved in the conversion of thyrotropin receptor-bound blocking-type immunoglobulin G (IgG) to the stimulating-type by anti-human IgG antibodies.

It has been reported that the addition of antibody (Ab) against human immunoglobulin G (IgG) converts TSH receptor-bound blocking-type IgG to stimulating-type IgG. However, the detail of converting mechanism remains unclear. In this study we examined the mechanism involved in this conversion using FRTL-5 cells. Blocking-type IgG was obtained from a patient with hypothyroidism. FRTL-5 cells were first incubated with IgG solution, then washed with PBS and exposed to antihuman IgG Ab. The effect of antihuman IgG Ab on converting activity was dose dependent. Maximal stimulation of cAMP was achieved with an antiserum dilution of 1:75. It seems likely that antimicrosomal Ab does not interfere with cAMP production, since IgG with a high anti-hemagglutination antibody titer did not show converting activity. Of the several kinds of antibodies tested, Ab against human IgG-Fab fragment was the most effective in converting ability, while the least effective were those against human IgG-Fc fragment. Although the divalent F(ab')2 fragment of antihuman IgG was significantly more effective in its converting ability than the monovalent Fab fragment, the Fab fragment itself also converted blocking IgG to the stimulating type in a dose-dependent manner. Accordingly, receptor cross-linking or aggregation does not play a major role in promoting this converting phenomenon. When cells were first exposed to blocking-type IgG and then to both antihuman IgG Ab and bovine TSH, cAMP production was much greater than the sum of each alone. However, anti-IgG Ab alone did not affect the binding of blocking-type IgG to receptor. These results suggest that the addition of antihuman IgG Ab not only converts blocking-type IgG to the stimulating type but also recovers TSH activity via a postreceptor step. Forskolin, like TSH, showed an additive effect on cAMP stimulatory action with antihuman IgG. In contrast, cholera toxin and antihuman IgG Ab were not additive. The reason for this discrepancy remains unknown. In summary, our observation indicates that 1) the converting phenomenon is induced via IgG-TSH receptor complexes; 2) the mechanism aside from receptor aggregation, i.e. the recognition of a critical domain in TSH receptor molecule, seems necessary for promoting converting phenomenon; and 3) the addition of antihuman IgG Ab affects a postreceptor step via TSH receptor structures that differ from the TSH-binding site.

Adult↗

Chronic thyroiditis with painful tender thyroid enlargement and transient thyrotoxicosis.

Clinical and laboratory findings and long term outcome (1.5-9 yr) in 7 women and 1 man with chronic thyroiditis (CT) who had painful tender thyroid enlargement were evaluated and compared with those in 11 women with subacute thyroiditis (SAT). Histological features consistent with SAT were not demonstrable, and various forms of CT (fibrous variant, diffuse, or focal lymphocytic thyroiditis) were observed. There were no differences in mean age, duration of symptoms, erythrocyte sedimentation rate, and C-reactive protein values in the 2 diseases. Seven patients had a history of goiter, and none had a history of a preceding upper respiratory tract infection. The mean white blood cell count was significantly lower in CT than in SAT patients. Six CT patients had transient thyrotoxicosis with a marked depression of radioactive iodine uptake. Mean serum T4 and T3 levels and T3 to T4 ratio in these 6 patients did not differ from those in the SAT patients. Five (all with high antimicrosomal antibody titers) of 8 CT patients developed persistent hypothyroidism. In contrast, none of the SAT patients became permanently hypothyroid. TSH binding inhibitory immunoglobulins and thyroid stimulation-blocking antibody at recent examination were negative in these 5 patients. Patients with this disorder present with transient thyrotoxicosis, with a marked depression of the thyroid radioactive iodine uptake, and often develop goitrous or atropic persistent hypothyroidism. This disorder may represent acute exacerbation of an underlying immunological process during the course of CT. To differentiate this syndrome from SAT, thyroid biopsy is necessary.

Adult↗

Alteration in expression of smooth muscle alpha-actin associated with transformation of rat 3Y1 cells.

Expression of actin was examined in a cultured rat embryonic cell line 3Y1 and transformed cell lines that originated from 3Y1. An alpha-actin in addition to cytoplasmic beta- and gamma-actins was detected in 3Y1 by two-dimensional gel electrophoresis. This alpha-actin was hardly detected at all in the transformants induced by Rous sarcoma virus, v-H-ras oncogene or adenovirus type 12, while the alpha-actin was retained in the transformed cell lines induced by N-methyl-N'-nitro-N-nitrosoguanidine or in SV40, which are cell lines of relatively low malignancy. Western and Northern blot analyses established that this alpha-actin was a smooth muscle alpha-isoform. An immunofluorescence study revealed that smooth muscle alpha-actin in 3Y1 cells is present in stress fibers. Thus, smooth muscle alpha-actin is also a component of actin stress fibers, as beta- and gamma-actins are in 3Y1 cells. An alteration in the expression of this actin isoform may be related to phenotypical changes accompanying transformation.

Actins↗

Granulocyte-macrophage colony-stimulating factor suppresses induction of neutrophil alkaline phosphatase synthesis by granulocyte colony-stimulating factor.

We evaluated the in vitro effects of recombinant human (rh) granulocyte colony-stimulating factor (G-CSF) and rh granulocyte-macrophage CSF (GM-CSF) on neutrophil alkaline phosphatase (NAP) activity and the incorporation of amino acids into polymorphonuclear leukocytes (PMN) from normal individuals and patients with chronic myelogenous leukemia (CML). Both the NAP activity and incorporation of amino acids into PMN were enhanced by the addition of G-CSF in a dose-dependent manner. NAP activity induced by G-CSF in PMN from CML patients showed a greater increase than that in PMN from normal controls. In contrast to G-CSF, GM-CSF did not affect the NAP activity in PMN in spite of the enhanced incorporation of amino acids into PMN by GM-CSF. Interestingly, both the NAP-inducing ability of G-CSF and its enhancing ability for amino acid incorporation were suppressed by GM-CSF in a dose-dependent manner when PMN were incubated with various concentrations of GM-CSF in addition to 100 ng/ml of G-CSF. These observations suggest that G-CSF and GM-CSF act differently: G-CSF induces NAP synthesis in PMN, whereas GM-CSF negatively modulates the effect of G-CSF. Further, it is suggested that protein synthesis induced by G-CSF is negatively modulated by GM-CSF in a general fashion.

Alkaline Phosphatase↗

Three patients who spontaneously developed persistent hypothyroidism during or following treatment with antithyroid drugs for Graves' hyperthyroidism.

Three patients with Graves' disease who spontaneously developed hypothyroidism after treatment with antithyroid drugs are described herein. Patient 1 developed a painful tender thyroid enlargement with a fever and accelerated erythrocyte sedimentation rate when she was receiving maintenance therapy with methimazole, and she progressed to persistent hypothyroidism with increased titers of antithyroglobulin and antimicrosomal antibodies and marked reduction of goiter size within the subsequent 2 months. Thyroid-stimulating hormone-binding inhibitory immunoglobulins (TBIIs) and thyroid stimulation-blocking antibody (TSBAb) were absent when she was hypothyroid. Hypothyroidism probably resulted from autoimmune thyroid destruction due to subacute aggravation of Hashimoto's thyroiditis. During the clinical course of patient 2, accelerated erythrocyte sedimentation rate and later transient increases of antimicrosomal and antithyroglobulin antibody titers were observed repeatedly (four times), and she finally fell into overt hypothyroidism. She also had negative results of tests for TBII and TSBAb. Her hypothyroidism appeared to result from repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis. Patient 3 fell into hypothyroidism when receiving a small dosage of methimazole. The TBII and TSBAb were strongly active when she developed hypothyroidism, which thus seemed to be due to blocking antibody. Patients with Graves' hyperthyroidism may eventually progress to hypothyroidism later by several different mechanisms. Severe and sudden or slowly repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis is one mechanism. Another may be the appearance of a blocking antibody to the TSH receptor.

Adult↗