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Biomedical subjects

I Morimoto

Publications and source records attributed to I Morimoto.

At least 91 records · Page 5Linked to original sources

Effects of interleukin 1 on growth and adenosine 3',5'-monophosphate generation of the rat thyroid cell line, FRTL-5 cells.

We investigated the effects of IL-1, IL-2, IL-6, interferon-gamma and tumour necrosis factor-alpha on growth and cAMP generation of FRTL-5 cells. IL-1 produced a significant stimulation of [3H]thymidine incorporation into FRTL-5 cells without TSH, whereas IL-1 caused significant reductions in [3H]thymidine incorporation induced by TSH or forskolin, which is known as an adenylate cyclase activator. Intracellular cAMP generation of FRTL-5 cells was stimulated by IL-1, whereas TSH-stimulated cAMP generation was inhibited by IL-1. These effects of IL-1 was neutralized by addition of anti-IL-1 antibody. The studies suggested that IL-1 blocks the effects of TSH on proliferation and cAMP generation of FRTL-5 cells on a post-receptor site of TSH.

Animals↗

[Remarkable improvement of anemia by administration of recombinant human erythropoietin in a patient with aplastic anemia].

A 69-year-old female was admitted for pancytopenia. The hematological examination showed leukocytes 1,800/microliters, hemoglobin 5.3 g/dl and platelets 9.6 x 10(4)/microliters. A bone marrow aspiration revealed hypoplasia, but no abnormal cells. Serum erythropoietin titer was 5,100 mU/ml. Diagnosis of aplastic anemia was made. She received 400 ml of blood transfusion twice, and was then treated with recombinant human erythropoietin (rHuEPO) (12,000 U/day) three times a week for eight weeks. Hemoglobin level gradually increased to the level of 12.0 g/dl. This case suggests that there are some cases of aplastic anemia which can respond to treatment with rHuEPO.

Aged↗

[Non-Hodgkin's lymphoma with marked infiltration in calf muscle].

A 64-year-old male developed pain and marked swelling of his left calf muscle in September, 1989. Deep-vein thrombophlebitis was suspected, and therapy with warfarin sodium followed by urokinase was instituted. Because of unsatisfactory effect of the therapy, the patient was referred to another hospital on January 3rd 1990. A CT scan of the left leg showed a soft-tissue mass adjacent to the fibula. A biopsy of the mass revealed non-Hodgkin's lymphoma of diffuse medium-sized cell type. Immunohistologic examination confirmed B cell type. He was admitted to our hospital on January 31st 1990. A chest roentgenogram showed right pleural effusion. A CT scan of the abdomen revealed a space-occupying lesion in the liver. A Gallium scintigraphy showed markedly increased isotope uptake in the left calf and liver. He was classed as a Stage IV B. He responded well to combination chemotherapy with cyclophosphamide, THP-adriamycin, VP-16, and prednisolone and achieved a complete remission. Although prominent infiltration of lymphoma cells in skeletal muscles is rarely reported, it is important to perform the biopsy promptly when the mass is found in a muscle. In this case report, we describe a rare case of non-Hodgkin's lymphoma with muscle invasion presented as marked calf muscle swelling.

Humans↗

Interleukin-4 as a potent inhibitor of bone resorption.

A possible role of interleukin-4 (IL-4) in the regulation of bone turnover was assessed by employing a 45Ca prelabeled-fetal mouse long bone culture system. IL-4 inhibited the bone resorption stimulated by parathyroid hormone (PTH), PTH related protein (PTHrP), 1 alpha, 25, dihydroxy-vitamin D3 [1 alpha, 25 (OH)2 D3], interleukin-1 alpha and - 1 beta (IL-1 alpha, IL-1 beta) and prostaglandin E2 (PGE2). Anti-IL-4 on monoclonal antibody abolished the inhibitory effect of IL-4 on the bone resorption. These results suggest that IL-4 may play an important role on the inhibitory regulation of bone resorption.

Animals↗

Androgen metabolism in rat L6 myoblast cells; high formation of 5 alpha-androstane-3 alpha,17 beta-diol from testosterone.

We have studied androgen metabolism in L6 rat myoblasts. 4-androstene-3,17-dione (Adione), testosterone, 5 alpha-dihydrotestosterone (DHT), and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) were used for substrates and the amounts of metabolites formed from the respective substrates in the medium were determined. Conversion of Adione to testosterone was dominant over the reverse conversion. DHT formation from testosterone was low and did not change with the duration of incubation, whereas 3 alpha-diol formation increased in a time-dependent manner. Major metabolite of testosterone was not DHT but 3 alpha-diol. A large amount of 3 alpha-diol was formed from DHT, however, DHT formation from 3 alpha-diol was very low. These data indicate that L6 cells have high 5 alpha-reductase activity and suggest that DHT formed from testosterone is rapidly metabolized to 3 alpha-diol in these cells.

17-Hydroxysteroid Dehydrogenases↗

L-canavanine acts on suppressor-inducer T cells to regulate antibody synthesis: lymphocytes of systemic lupus erythematosus patients are specifically unresponsive to L-canavanine.

L-Canavanine (LC) is an amino acid contained in alfalfa seeds that provokes a disease state similar to systemic lupus erythematosus (SLE) in primates. In vitro experiments showed that LC stimulated proliferation of human phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) and T cells of healthy donors but not of pokeweed mitogen (PWM)-stimulated PBMC. LC inhibited spontaneous generation of immunoglobulin-secreting cells (ISC) of PBMC, while it enhanced ISC generation of CD8(-) cells. LC inhibited PWM-induced ISC generation of CD8(-) cells but not of CD4(-) cells, indicating that LC stimulates CD8(-) cells more strongly than CD4(-) cells. The stimulation index of lymphocyte proliferation (PHA + LC/PHA) was greater in CD8(-)Leu8(+) cells than CD8(-)Leu8(-) cells. The stimulation index was also higher in PBMC than in PBMC plus CD8(-)Leu8(-) cells, the former population containing relatively increased CD8(-)Leu8(+) cells. These findings suggest that LC acts mainly on CD8(-)Leu8(+) cells. That LC acts on CD8(-)Leu8(+) cells was confirmed by the finding that LC inhibited ISC generation of non-T plus CD4(+)Leu8(+), but not of non-T plus CD8(-)Leu8(-) cells. In addition, we found that PBMC of SLE patients were specifically unresponsive to LC stimulation. The stimulation index of lymphocyte proliferation (PHA + LC/PHA) in SLE patients (n = 16) was 0.97 +/- 0.19, whereas that in age-matched healthy control (n = 17) was 1.45 +/- 0.40 (P less than 0.001). Patients with active disease were especially unresponsive to LC. Its responsiveness did not correlate with the dose of prednisolone administered. These findings suggest that the lymphocyte response to LC depends primarily on the existence of functional CD8(-)Leu8(+) cells. Moreover, it appears that suppressor-inducer T cells, responsive to LC, are especially deficient in SLE.

Adolescent↗

Mutagenicity of isoquinoline alkaloids, especially of the aporphine type.

The mutagenicity of 44 isoquinoline alkaloids was tested in Salmonella typhimurium TA100 and TA98 in the presence or absence of S9 mix. The alkaloids tested included compounds from the isoquinoline, benzylisoquinoline, bisbenzylisoquinoline, monoterpene isoquinoline, berberine, morphinane, hasubanan, benzo[c]phenanthridine and aporphine groups. Among the alkaloids tested, liriodenine was the most potent mutagen for TA100 and roemerine was the most potent for TA98. A clear structure-mutagenicity relationship was observed in a series of aporphine alkaloids (aporphine, dehydroaporphine, 7-oxoaporphine and 4,5-dioxoaporphine), and 10,11-non-substituted aporphines were suggested to exert their mutagenicity through metabolic activation of the 10,11 positions, possibly as the 10,11-epoxides.

Alkaloids↗

Immunoreactive circulating alpha-interferon is low in Sjögren's syndrome.

Circulating alpha-interferon in plasma of 26 patients with Sjögren's syndrome was 0.069 +/- 0.034 ng/ml, a significant decrease compared with 0.119 +/- 0.051 ng/ml for age- and sex-matched healthy subjects (P less than 0.01) and compared with values previously found for healthy donors at ages 1-89 years. The results indicate the inability of Sjögren's syndrome patients to maintain circulating alpha-interferon.

Adult↗

Role of zinc in interleukin 2 (IL-2)-mediated T-cell activation.

In a serum-free culture containing no zinc, zinc enhanced the proliferation of T cells in response to interleukin 2 (IL-2), and also the in vitro production of IL-2 by T cells. Although the lymphocyte proliferation was partially inhibited by anti-IL-2 antibodies, it was completely inhibited by anti-IL-2 receptor (CD25) antibodies. A Scatchard plot analysis showed that zinc induced the expression of high-affinity receptors for IL-2 on lymphocytes. The results indicated that zinc may be essentially required for IL-2-mediated T-cell activation.

Cell Division↗

Inhibitory effect of IL-1 on the TSH dependent growth of rat thyroid cells (FRTL-5).

Using a functioning rat thyroid cell line (FRTL-5), we examined the effects of some cytokines, particularly interleukin-1 (IL-1) on the growth of thyroid cells. In 5H medium, namely Coon's modified Ham's F-12 medium supplemented with 5% calf serum and a five-hormone preparation consisting of insulin, hydrocortisone, transferrin, glycyl-L-histidyl-L-lysine acetate and somatostatin, IL-1 enhanced the growth of FRTL-5 cells detected by [3H]TdR incorporation. However, in 6H medium (5H medium plus bovine TSH), IL-1 inhibited the growth of FRTL-5 cells. Both effects were neutralized by the addition of anti-IL-1 antibody. Furthermore, IL-1 inhibited the growth of FRTL-5 cells induced by forskolin which is known as an adenylate cyclase activator. FRTL-5 cells have specific IL-1 receptors detected by the binding of 125I-labeled IL-1 alpha. By Scatchard plot analysis, the numbers and the dissociation constants of IL-1 receptors on FRTL-5 cells were shown to be 5225/cell and 8.69 x 10(-10) M. Interleukin-2, interleukin-6 and interferon-gamma (IFN-gamma) had no significant effects on the cell growth in 6H medium, while IFN-gamma and insulin-like growth factor I stimulated cell growth somewhat in 5H medium. These results suggest that IL-1 plays a regulatory role in the growth of thyroid cells through binding to the IL-1 receptors.

Animals↗

Age distribution of circulating alpha-interferon.

A sensitive radioimmunoassay showed that circulating alpha-interferon in the plasma of healthy individuals was low in children and reached the highest level in the young adult, then declined gradually with age. Circulating alpha-interferon was 0.201 +/- 0.059 ng/ml in males (n = 19) and 0.184 +/- 0.076 ng/ml in females (n = 14) at ages 30-39 years old. It was noted that circulating alpha-interferon was maintained up to a certain level even in elderly individuals.

Adult↗

Zinc inhibits pokeweed mitogen-induced development of immunoglobulin-secreting cells through augmentation of both CD4 and CD8 cells.

The mechanism whereby zinc regulates the in vitro antibody synthesis of human peripheral blood mononuclear cells was investigated. In a serum-free culture, zinc inhibited the pokeweed mitogen (PWM)-induced generation of immunoglobulin secreting cells (ISC) through an apparent non-specific augmentation of T-cells, which included CD4 and CD8 cells, as well as both CD8-Leu8+ and CD8-Leu8- cells. It was noted that CD4 cells were more stimulated than CD8 cells, and that CD8-Leu8- cells were more stimulated than CD8 Leu8+ cells. CD8-Leu8- cells inhibited the development of ISC. These findings indicate that, although zinc stimulates all T-cells, the relative potency of zinc differs among T-cell subsets; helper inducer T-cells appear to be most strongly stimulated.

Antibody-Producing Cells↗

Human epidermal growth factor for the stratification of synovial lining layer and neovascularisation in rheumatoid arthritis.

Immunohistochemical study showed selective localisation of human epidermal growth factor (hEGF) to the synovial lining layer. Although the synovial lining layer of the rheumatoid, osteoarthritic, and traumatic joints was hEGF positive, hEGF staining was especially dense at the rheumatoid synovial lining layer; the staining increasing linearly according to the degree of stratification of the lining layer (r = 1). Human epidermal growth factor was ultrastructurally localised to cytoplasm, especially to rough endoplasmic reticulum, of the synovial lining fibroblast-like (type B) cell. Only the cell surface of macrophage-like (type A) cells was hEGF positive. When different histological variables were compared with each other a positive correlation was found between hEGF staining of the synovial lining layer and the degree of neovascularisation of rheumatoid synovium (r = 0.72). Although some lymphocytes were weakly hEGF positive, neovascularisation did not correlate with the extent of lymphocyte infiltration or of hEGF staining of lymphocytes. Lymphocyte infiltration or hEGF staining of lymphocytes did not correlate with hEGF staining of the synovial lining layer, whereas the lymphocyte infiltration correlated positively with the extent of perivascular accumulation of lymphocytes (r = 0.89). These findings suggest that (a) hEGF is synthesised by and secreted through endoplasmic reticulum and Golgi apparatus from the synovial lining type B cell; (b) hEGF is at least partially responsible for the pathogenesis of stratification of the rheumatoid synovial lining layer, and perhaps of neovascularisation of the rheumatoid synovium, whereas it is not responsible for lymphocyte accumulation to the rheumatoid synovium.

Arthritis, Rheumatoid↗

Radioimmunoassay of circulating alpha-interferon with reference to aging and osteoporosis.

Circulating immunoreactive alpha-interferon in elderly individuals was 0.139 +/- 0.042 ng/ml in males and 0.111 +/- 0.033 ng/ml in females at ages 70-79, and 0.120 +/- 0.045 ng/ml in males and 0.105 +/- 0.039 ng/ml in females at ages 80-89. These values were significantly lower than those in young adults (p less than 0.01), but higher compared with the values found in disease states including rheumatoid arthritis (p less than 0.0025). There was no correlation between circulating alpha-interferon and bone mass indices, such as bone mineral content or quantitative computed tomography values, in these elderly individuals. Circulating alpha-interferon was, however, significantly increased in senile osteoporotic patients after 2 months of treatment with 1 alpha-hydroxyvitamin D3 or calcitonin, whereas it was unaltered in patients receiving ipriflavone or in nonosteoporotic individuals without medication. These findings indicate that circulating alpha-interferon, which is highest in young adults, declines with aging. It appears that circulating alpha-interferon is maintained at a certain steady-state level in healthy elderly individuals. Although there was no apparent relationship between bone mass indices and circulating alpha-interferon, it is possible that bone and cellular metabolism related to vitamin D3 may be contributing factors for the maintenance of circulating alpha-interferon.

Aged↗

A mutagenic new iridoid in the water extract of catalpae fructus.

A mutagenic principle in the water extract from Catalpae Fructus (originated from Catalpa ovata G. DON) (Bignoniaceae) was isolated and characterized as a new iridoid named catalpin. The iridoid exhibited mutagenic activity towards Salmonella typhimurium strain TA100 in the presence and absence of rat liver homogenate (S9) mix in Ames' test.

Animals↗

A study on immunological effects of L-canavanine.

L-canavanine (LC) is an amino acid contained in alfalfa seeds that provokes a disease state similar to systemic lupus erythematosus (SLE) in primates. In vitro experiments show that LC mainly acts on CD8(-)Leu8(+) T cells to regulate antibody synthesis and lymphocyte proliferation. The lymphocytes of SLE patients were poorly responsive to LC stimulation, suggesting that CD8(-)Leu8(+) T cells are specifically deficient in SLE. Although the precise mechanism of intracellular action of LC is not yet clear, we found that the intracellular calcium level [( Ca2+]i) increased in response to LC. This increase in [Ca2+]i may be partially responsible for the mechanism of action of LC on lymphocytes.

Antibody-Producing Cells↗