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Biomedical subjects

M Kawano

Publications and source records attributed to M Kawano.

At least 271 records · Page 15Linked to original sources

Production of interleukin 1 beta, a potent bone resorbing cytokine, by cultured human myeloma cells.

Supernatants of freshly isolated human myeloma cell cultures were examined both for bone-resorbing activity (BRA) in vitro using newborn mouse calvaria, and for identification of the causal substances of the BRA. Eight of 14 culture supernatants of myeloma cells had BRA. All of these BRA-positive supernatants were from patients with marked destructive bone lesions of multiple myeloma. The presence of interleukin 1 (IL-1), especially IL-1 beta, was demonstrated in seven of these BRA-positive supernatants but not in BRA-negative supernatants. The concentrations of IL-1 beta were high enough to induce bone resorption in the newborn mouse calvaria assay and the BRA was totally abolished by pretreatment of the supernatants with anti-IL-1 beta antibody but not with either anti-IL-1 alpha antibody or normal serum. Other bone resorbing cytokines such as tumor necrosis factor or lymphotoxin were not present in high enough concentrations to stimulate bone resorption and their levels did not correlate with the BRA. IL-1 beta mRNA was also identified in BRA-positive myeloma cells. These results demonstrate that IL-1 beta is the principal agent of BRA present in supernatants of myeloma cell cultures, and also identify a possible role of IL-1 beta in destructive bone lesions in patients with multiple myeloma.

Adult↗

Interleukin-1 beta rather than lymphotoxin as the major bone resorbing activity in human multiple myeloma.

Human myeloma cells were purified from bone marrow aspirates from four patients having advanced myeloma, including one with common acute lymphoblastic leukemia antigen-positive myeloma. All of these myelomas had marked bone lytic lesions. From the culture supernatants of these purified myeloma cells, bone-resorbing activities were significantly revealed by 45Ca-release bone resorption assay, and IL-1 activities were also detected by IL-1 bioassay (mouse thymocyte comitogenic assay). Sandwich enzyme immunoassay for IL-1 alpha or IL-1 beta revealed that IL-1 beta was responsible for IL-1 activity of these culture supernatants. Furthermore, the bone resorbing activities of these culture supernatants were completely neutralized by pretreatment of anti-IL-1 beta, but not anti-IL-1 alpha antibody. By Northern blot analysis, IL-1 beta mRNA was identified from these myeloma cells. Therefore, it is concluded that myeloma cells produce IL-1 beta, which acts as bone-resorbing activity in multiple myeloma.

Antigen-Antibody Reactions↗

The cause of nasal sinusitis in patients with cleft palate.

To determine the reason for the high incidence of nasal sinusitis in patients with cleft palate, the type of cleft, degree of nasal septal deviation, velopharyngeal function, and presence of pharyngeal flap were investigated in relation to nasal sinusitis. We also examined the relationship between the side of sinusitis and the cleft side in patients with unilateral cleft palate. Development of maxillary sinus, nasal mucociliary transport, and ciliary beating frequency of ciliated cells were also examined. The saccharin test indicated that nasal mucociliary transport was impaired. This impairment is believed to be one of the reasons for the high incidence of sinusitis in patients with cleft palate.

Cleft Palate↗

Altered cytokine activities are related to the suppression of synthesis of normal immunoglobulin in multiple myeloma.

The content of peripheral blood B cells (B1+) was reduced in patients of multiple myeloma (MM) and not in those with benign monoclonal gammopathy (BMG) compared to normal donors (P less than 0.01). This observation correlated with the suppression of synthesis of normal immunoglobulin (Ig) in MM. Thus, cytokine activities regulating the proliferation of normal mature B cells, such as B cell stimulatory factor 1 (BSF-1)/interleukin 4 (IL-4), B cell growth inhibitory factor (BIF) and IL-2 in peripheral blood T cells, and IL-1 in peripheral blood adherent cells, were investigated in patients with BMG (n = 7) and MM (n = 28). All patients of MM having a marked suppression of synthesis of all other normal Ig, had significantly lower levels of BSF-1 activity and inversely higher levels of BIF activity than those of normal donors. However, patients with BMG having no suppression of synthesis of normal Ig had BSF-1 and BIF activities similar to normal donors. There was no significant difference in IL-1 and IL-2 activities between both normal donors and BMG versus MM patients. These data show that in MM altered cytokine activities correlate with suppression of synthesis of normal Ig.

B-Lymphocytes↗

BSF-2/IL-6 does not augment Ig secretion but stimulates proliferation in myeloma cells.

Human myeloma cells were highly purified from bone marrow aspirates of 21 patients with advanced immunoglobulin G (IgG)-type multiple myeloma. B-cell stimulatory factor 2 (BSF-2)/interleukin-6 (IL-6) was originally characterized as a cytokine that can enhance immunoglobulin secretion from activated normal B cells and increase the expression of secretory-type Ig mRNA in these B cells, but that does not augment proliferation of activated B cells. However, recombinant IL-6 (rIL-6) could not enhance M-protein (IgG) secretion in freshly isolated myeloma cells in vitro but could augment proliferation of myeloma cells, although myeloma cells constitutively expressed IL-6 receptors. Furthermore, expression of secretory-type IgG (gamma-chain) mRNA in myeloma cells was not changed in the presence of IL-6. These results show that IL-6 is not an enhancing factor in Ig secretion from myeloma cells, and thus signal transduction through IL-6 in myeloma cells may be altered as opposed to activated B cells.

Adjuvants, Immunologic↗

An experimental study of percutaneous absolute ethanol injection therapy for small hepatocellular carcinoma: effects of absolute ethanol on the healthy canine liver.

As a basic study of percutaneous ethanol injection therapy (PEIT) under ultrasound guidance, 1 ml of absolute ethanol was injected into the healthy liver of adult mongrel. Ultrasonographic, macroscopic and histologic studies of the injection site were carried out chronologically and the mechanism for cell necrosis was evaluated. It was concluded that absolute ethanol injected to the healthy mongrel liver caused not only direct cell damage due to potent fixative effect through deprivation of fluid from cells, but also indirect cell damage due to impairment of tissue blood flow related to thrombus formation, which resulted in necrosis. Moreover, disappearance of acoustic shadow (AS) was considered to be due to absorption or removal of the gases, which were the air in the PTC needle injected into the liver and the evaporated oxygen from denatured oxyhemoglobin (HbO2), and the denatured red blood cells after improvement of blood flow at the surrounding area of the injection site. Gradual attenuation of the echogenicity might reflect the progression of necrosis at the injection site recognized histologically.

Animals↗

An assay method for ganglioside synthase using anion-exchange chromatography.

A rapid procedure which is based on combined ion-exchange chromatography and solubility was established for determination of the activity of ganglioside synthases and cerebroside sulfotransferase. The procedure consists of selective elution of radiolabeled reaction products (acidic glycolipids) freed from labeled precursors and breakdown products on a DEAE-Sephadex column and of direct radioassay of the products in the eluate. Monosialogangliosides were eluted from the column with 40 mM ammonium acetate (AcONH4) in methanol, cerebroside sulfate with 90 mM AcONH4 in methanol, and disialogangliosides with 40 mM AcONH4 in isopropanol/n-hexane/water (55/20/19, v/v/v). The established procedure is simple, reproducible, and economical. Using rat Golgi membrane as enzyme source the recovery rate of the products was over 95%.

Animals↗

Heterogenous response of B cell chronic lymphocytic leukaemia (B-CLL) cells to anti-human IgM antibody (anti-mu) and B cell stimulatory factor 1 (BSF-1).

B cell chronic lymphocytic leukaemia (B-CLL) cells from seven patients were examined for 3H-TdR uptake with anti-human IgM antibody (anti-mu) and B cell stimulatory factor 1 (BSF-1)/IL-4. B-CLL cells from one patient could proliferate with anti-mu plus BSF-1, but not with BSF-1 alone. B-CLL cells from two patients responded to BSF-1 alone; one could proliferate more by adding anti-mu, but the proliferation of the other cells was inhibited by adding anti-mu. On the other hand, B-CLL cells from the other four patients responded neither to anti-mu nor to anti-mu plus BSF-1. Surface densities of membrane IgM of B-CLL cells were also analysed by fluorescence activated cell sorter (FACS), but there was no correlation between proliferative response (DNA synthesis) of B-CLL cells to anti-mu and densities of surface membrane IgM. These results show that there is a functional heterogeneity of B-CLL cells with regard to proliferative response to anti-mu and BSF-1.

Aged↗

Autogenic training as an effective treatment for reflex neurovascular dystrophy: a case report.

A 15-year-old girl complained of swelling and shooting pains in the right upper extremity, which had bothered her for seven months. Physical examination revealed swelling, cyanosis, weakness and hyperesthesia over the entire right upper extremity. Serological and biochemical data were within normal limits. She was diagnosed as having reflex neurovascular dystrophy (RND). Psychological problems with school and her family might have contributed to the pathogenesis of the disease. With autogenic training (AT), remission was obtained within eighteen months.

Adolescent↗

[A case of refractory multiple myeloma demonstrating a relationship between the progression of the disease and in vitro myeloma cells activity].

In vitro proliferation (3H-TdR-uptake) and M-protein secretion rate by highly purified myeloma cells from bone marrow aspirates were examined serially to evaluate the progression of multiple myeloma in a patient who was refractory to conventional alkylating agents. Following the administration of IFN-alpha, serum M-protein decreased significantly, with the reduced in vitro spontaneous M-protein secretion rate from the separated myeloma cells. Similarly, when IFN-alpha as low as 10 u/ml was added in vitro, it also suppressed M-protein secretion from myeloma cells of this patient, suggesting that, the observed decrease of serum M-protein was due to diminished M-protein secretion by the myeloma cells themselves, as well as the reduction of the tumor cell burden. On the other hand the in vitro 3H-TdR uptake by the myeloma cells increased markedly with the decrease in the M-protein secretion rate. Five months after the initiation of IFN-alpha treatment, tumor formation at the lumbar vertebrae occurred when serum M-protein level was still low, followed by a bone marrow relapse. These results suggest that serial assessments of proliferation and M-protein secretion potential of myeloma cells in vitro can be helpful in predicting the progression of multiple myeloma.

Cell Division↗

[Adrenal incidentaloma--report of 14 operated cases and analysis of 4-year autopsy series of Japan].

During the last 7 years, operation was performed for 94 cases of adrenal tumor in our series, of which 14 were incidentally found by abdominal computed tomography or echography. They included 9 cases of pheochromocytoma, 1 of Cushing's syndrome, 3 of ganglioneuroma and 1 of cortical adenoma. Five of 9 pheochromocytoma cases were devoid of hypertension, but all 9 cases had abnormally high levels of urinary catecholamines and/or their metabolites. The 4-year autopsy series of Japan (1980-1983) included about 153,000 cases. Except the metastatic tumors, the following lesions were incidentally found in the adrenal gland: 310 of cortical adenoma, 153 of cortical hyperplasia, 39 of pheochromocytoma and 17 cases of neurogenic tumors. Some of the cortical adenomas are presumed to be more than 1 cm in diameter. So, they are expected to be found incidentally, more frequently in the future. Surgery is not necessary for most of them, except for functioning tumors. Most of the pheochromocytomas are presumed to be hormonally active, and should be treated surgically. It is probable that these functioning tumors had been missed clinically, especially in the elderly persons. Neurogenic tumors and myelolipomas may be left in place, when malignancy can be ruled out.

Adenoma↗

Cytokines as autocrine growth factors in malignancies.

Interleukin 6 (IL-6) was originally characterized as a B-cell differentiation factor, responsible for the terminal maturation of activated B cells to immunoglobulin producing cells. Recent works reveal that IL-6 has a wide variety of biological functions on various cells. In particular, IL-6 has been shown to augment the growth of freshly isolated human myeloma cells, and the myeloma cells constitutively produce IL-6 and express IL-6 receptors. Moreover, it has been shown that anti-IL-6 antibody can inhibit the in vitro growth of the myeloma cells. This is direct evidence that an autocrine loop is operating in freshly isolated myeloma cells, and that a constitutive production of IL-6 and activation of the IL-6 gene could be involved in the oncogenesis of human myeloma.

Animals↗

Interleukin-1 accelerates autocrine growth of myeloma cells through interleukin-6 in human myeloma.

Recombinant interleukin 1 alpha (rIL-1 alpha) augmented proliferation of freshly isolated myeloma cells as well as B-cell stimulatory factor 2 (BSF-2)/interleukin-6 (IL-6). Recombinant IL-1 alpha-induced proliferation was partially inhibited by anti-IL-6 antibody. In the culture supernatants of rIL-1 alpha-stimulated myeloma cells, IL-6 activities, which were measured by using an IL-6-dependent murine hybridoma clone, MH60.BSF2, were increased, when compared with those in the culture supernatants of nonstimulated myeloma cells. Furthermore, IL-6 messenger RNA (mRNA) expression was also augmented in IL-1 alpha-stimulated myeloma cells. Therefore rIL-1 alpha stimulates myeloma cells to produce IL-6, which consequently augments proliferation of myeloma cells. Thus, IL-1 can accelerate autocrine growth of myeloma cells through IL-6.

Adjuvants, Immunologic↗

Sensitive inhibitory effect of interferon-alpha on M-protein secretion of human myeloma cells.

The effects of interferon-alpha (IFN alpha) on in vitro proliferation and M-protein secretion in human myeloma cells were investigated. Human myeloma cells were purified from bone marrow aspirates in 12 multiple myeloma patients. Purified myeloma cells were cultured for 48 hours with IFN alpha at its lower concentrations (0.1 to 100 U/mL). The cells were then pulsed with 3H-TdR for the last 12 hours and 3H-TdR uptake was measured (in vitro proliferation). After 48-hour culture, supernatants were harvested and the amount of M-protein in these fluids were measured by enzyme-linked immunosorbent assay (ELISA) (in vitro M-protein secretion). In vitro M-protein secretions of myeloma cells were significantly suppressed even at 0.1 U/mL of IFN alpha, while 3H-TdR uptakes were not so suppressed until 10 or 100 U/mL of IFN alpha were added. The expressions of secretory immunoglobulin (Ig) mRNA of these myeloma cells were also selectively suppressed by IFN alpha. Furthermore, after IFN alpha had been administered intramuscularly, 3 to 6 x 10(6) U/d for at least 1 month, in vitro M-protein secretions of these myeloma cells were decreased compared with those before IFN alpha administration. Therefore, these results suggest that IFN alpha has more sensitive inhibitory effect on M-protein secretion of human myeloma cells rather than on myeloma cell proliferation.

Blood Proteins↗