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Biomedical subjects

M Kawano

Publications and source records attributed to M Kawano.

At least 289 records · Page 16Linked to original sources

[Confirmation of the presence of adrenergic fibers in human umbilical cord by electron microscopy].

1) In order to visualize biogenic catecholamine, the FAGLUPAGAS method, a new modification of the glyoxylic acid method, was used. Catecholaminergic fibers were observed chiefly in the intraarterial and surrounding region of arteries within Wharton's jelly. Periarterial plexus formation was also observed only in part of the umbilical cord near the umbilical ring. 2) Because first of all we had succeeded in detecting longitudinally running catecholaminergic fibers forming a periarterial plexus, we were able to prepare ultrathin sections exactly parallel to such fibers, and succeeded in confirming the presence of adrenergic fibers in human umbilical cord by electron microscopy.

Adrenergic Fibers↗

Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas.

Human B cell stimulatory factor 2 (BSF-2) was originally characterized and isolated as a T cell-derived factor that caused the terminal maturation of activated B cells to immunoglobulin-producing cells. Molecular cloning of the complementary DNA predicts that BSF-2 is a protein of relative molecular mass (Mr) 26,000 similar or identical to interferon beta 2, hybridoma plasmacytoma growth factor and hepatocyte stimulating factor. IL-6 has been proposed as a name for this molecule. It is now known that BSF-2 has a wide variety of biological functions and that its target cells are not restricted to normal B cells. Responses are also seen in T cells, plasmacytomas, hepatocytes, haematopoietic stem cells, fibroblasts and rat phoeochromocytoma, PC12 (Satoh, T. et al., manuscript in preparation). Of particular interest to this report is that human BSF-2 is a potent growth factor for murine plasmacytomas and hybridomas. This observation suggested to us that constitutive expression of BSF-2 or its receptor could be responsible for the generation of human myelomas. In this study we report that myeloma cells freshly isolated from patients produce BSF-2 and express its receptors. Moreover, anti-BSF-2 antibody inhibits the in vitro growth of myeloma cells. This is direct evidence that an autocrine loop is operating in oncogenesis of human myelomas.

Antibodies↗

Three cases of untreated classical PKU: a report on cataracts and brain calcification.

There are only four previous reports of cataracts in untreated classical phenylketonuria (PKU) patients. Brain calcification, which has been known to occur in patients with dihydropteridine reductase (DHPR) deficiency, has been reported, as far as we know, in only one (albeit unusual) case. We report on three patients with untreated classical PKU; all have cataracts and normal serum levels of glucose and galactose. One of the patients (whose endocrinological tests and biochemistry including folate were normal) has bilateral brain calcifications remarkably similar to that seen in DHPR deficiency. To what extent cataracts and brain calcification occur with classical PKU is unknown because of the lack of case reports addressing these symptoms. Our cases combined with previous reports call attention to the fact that they may be frequently overlooked manifestations of classical PKU.

Adult↗

A major 50-kDa human B-cell growth factor-II induces both Tac antigen expression and proliferation by several types of lymphocytes.

Many cytokines have been documented to have a multiplicity of biological effects by acting on a variety of cells. In order to determine whether human BCGF-II acts on any cells in addition to normal B cells, the effect of human BCGF-II on murine thymocytes, human peripheral blood T cells, a human natural killer-like cell line, YT, and Epstein-Barr virus (EBV)-transformed B-cell lines was further examined. BCGF-II augmented incorporation of [3H]thymidine by murine thymocytes in combination with suboptimal doses (0.5 microgram/ml) of concanavalin A (Con A) but not at lower doses (0.1 microgram/ml) of Con A, a concentration usually used for interleukin 1 (IL-1) assays. BCGF-II could not induce proliferation or Tac antigen (Ag) expression on normal peripheral blood T cells stimulated with OKT3 antibody. Both proliferation and Tac Ag expression on YT cells were also augmented by BCGF-II. BCGF-II induced both high- and low-affinity IL-2 receptor (IL-2R) on YT cells as determined by 125I-IL-2-binding assay. Two of seven EBV-transformed B-cell lines tested (ORSON and AUM cells) in response to BCGF-II exhibited augmentation of proliferation and cell surface Tac Ag expression. BCGF-II in the presence of low doses (0.1 microgram/ml) of phorbol myristate acetate (PMA) also induced Tac Ag mRNA (3.5 and 1.5 kb) in these B-cell lines. The IL-2R induced on these B-cell lines, however, consisted mostly of low-affinity receptors. Both Tac Ag and its mRNA in these B-cell lines were not induced by Forskolin but by PMA, suggesting that this induction may involve protein kinase C. The present study shows that human BCGF-II can stimulate YT cells, murine thymocytes, and some EBV-transformed B-cell lines but not peripheral blood T cells. Consequently, BCGF-II can induce the growth and differentiation of a number of cell types in addition to normal B cells.

Animals↗

The significance of prostacyclin produced by pregnant rat myometrium: the relationship between myometrial prostacyclin producing activity and passive stretch of myometrium by growing conceptus.

The present experiment was performed to elucidate the significance of prostacyclin (PGI2) produced by pregnant rat myometrium. PGI2-like substance producing activity of various portions of the uterus was measured at selected gestational stages by platelet bioassay; surface area per 1 gm of uterine wall enveloping one conceptus was calculated; and spontaneous contractility of myometrium of both conceptus and non-conceptus regions and the effects of authentic PGI2 on it were examined. PGI2-like substance producing activity increased with advancing pregnancy, but the activity varied according to area of the myometrium, being highest in the area where it was most greatly stretched by the growing conceptus and lowest where no conceptus was contained. Spontaneous contractility was reduced in regions with high PGI2 producing activity. Though authentic PGI2 generally exhibited a stimulatory effect, it had an inhibitory effect on Day 10 pregnant myometrium. From these results, it may be concluded that the producing activity of PGI2, which remarkably increases in the conceptus region with the advance of pregnancy, keeps the uterine wall relaxed, making the uterus adapt to the growth of the fetus. Passive myometrial stretch by the growing conceptus is thought to be one of factors which enhance myometrial PGI2 producing activity.

Animals↗

[Endocrinological and electron microscopical studies on the complete form of testicular feminization syndrome].

A 23-year-old patient with a complete form of testicular feminization syndrome (Tfm) was examined endocrinologically and morphologically by electron microscopy. 1. Serum testosterone, DHEA and estrone concentrations and the urine 17-KS concentration were higher than in adult males. Furthermore, serum pituitary gonadotropins, especially LH, were increased. 2. We found that testicular venous testosterone, estrone, estradiol and progesterone were remarkably increased compared with their peripheral concentrations, and that circulating concentrations decreased rapidly after gonadectomy. The electron microscopic study showed active steroidogenesis in Leydig cells. We believe that these results prove that these steroids are produced in Leydig cells. 3. We found that the administration of 10,000 IU/day of hCG for 2 days increased serum gonadal steroids but that of 225 IU/day of hMG for 2 days did not, that LH responded strongly to LH-RH but FSH response was weak, and that after gonadectomy serum LH immediately increased but FSH did not change for at least 24 hours. From these results, we assume that FSH is not related to steroidogenesis and that the mechanisms regulating serum LH and FSH are different. 4. The seminiferous tubules were occupied by two kinds of cells. Both kinds were Sertoli cells, one of which was numerous and of low electron density indicating an immature type, and the other was of high electron density indicating a mature type. Spermatogonia were not detected.

Adult↗

Decrease in BSF-2/IL-6 response in advanced cases of multiple myeloma.

Human myeloma cells freshly isolated from 40 patients with IgG multiple myeloma (MM, 10 in stage I and 30 in stage III), were cultured for 48 hours with recombinant B cell stimulatory factor 2 (rBSF-2)/interleukin-6 (IL-6), which is considered a major growth factor for myeloma cells. Uptake of 3H-thymidine by these purified myeloma cells was measured, and BSF-2 response was evaluated by stimulation index and delta cpm induced by rBSF-2. Myeloma cells from cases in stage I responded to rBSF-2 better than those in stage III. Moreover rBSF-2 responders also showed better response to chemotherapy. Therefore, these results suggest that in vitro response of myeloma cells to BSF-2 correlates with disease progression and clinical response in patients of MM.

Humans↗

Separation of human myeloma cells from bone marrow aspirates in multiple myeloma and their proliferation and M-protein secretion in vitro.

Human myeloma cells were purified from bone marrow aspirates from patients with multiple myeloma (MM) by Percoll discontinuous density-gradient centrifugation, E rosette formation and treatment with antimyelomonocytic antibody (Leu M1), plus complement. Thus, the purified cell fraction consisted of greater than 90% myeloma cells, even when as little as 15% myeloma cells were contained in bone marrow mononuclear cell fraction, determined by morphological and immunologic examinations. With highly purified myeloma cells from 29 patients with IgG type MM, biologic characteristics such as spontaneous proliferation (3H-TdR uptake) and M-protein secretion rate in vitro were evaluated. Both activities varied among patients within stage I and III, and a 3H-TdR uptake of 255-24, 132 cpm/4 x 10(4) cells, and an M-protein secretion rate of 9 to 72 pg/cell/day, respectively, were recorded. However, in each patient, there was no correlation between 3H-TdR uptake and M-protein secretion rate. These results thus suggest that 3H-TdR uptake and M-protein secretion rate of highly purified myeloma cells are independent biologic parameters, not associated with the clinical stages, and the purification of myeloma cells we describe can contribute to further studies on the biologic characteristics and to understanding of the pathophysiology involved in MM.

Blood Proteins↗

Identification of a major 50-kDa molecular weight human B-cell growth factor with Tac antigen-inducing activity on B cells.

A bioassay was developed using human small B cells adherent to anti-human IgM (anti-mu)-coated wells. These B cells were stimulated to proliferate by culture supernatants of concanavalin A (Con A)-activated human peripheral blood lymphocytes (Con A Sup) even in the presence of high concentrations of anti-mu coated on assay wells. Human B-cell growth factor (BCGF) activities were partially purified from Con A Sup. Preparative chromatography (Sephacryl S-200 and isoelectrofocusing) yielded a major peak of BCGF activity for B cells adherent to anti-mu-coated wells with a molecular weight of 50,000 (50 kDa) and a pI 7.6. The 50-kDa BCGF was further purified by sequential chromatography using DEAE-Sephacel, CM-Sepharose, Sephacryl S-200, CM-high performance liquid chromatography (HPLC), and hydroxyapatite (HA)-HPLC. The HA-HPLC-purified 50-kDa BCGF was free of interleukin-1 (IL-1), interleukin-2 (IL-2), and interferon activities, but could support growth of BCL1 cells, similar to BCGF-II. Neither IL-1 nor interferon-gamma had any growth-stimulating effect in our B-cell proliferation assay with or without BCGF in Iscove's synthetic assay medium. BCGF-induced proliferation of B cells adherent to anti-mu-coated wells could be markedly augmented by the simultaneous or sequential addition of recombinant human IL-2 (rIL-2). When cultured for 3 days with 50-kDa BCGF, about 40% of B cells adherent to anti-mu-coated wells expressed Tac antigen, and monoclonal anti-Tac antibody inhibited rIL-2 enhancement of proliferation of 50-kDa BCGF-preactivated B cells. In addition, 50-kDa BCGF could induce Tac antigen on an Epstein-Barr virus-transformed B-cell line (ORSON) in the presence of a suboptimal dose of phorbol myristate acetate (PMA) and also on a natural killer-like cell line (YT cells). We have therefore identified a major 50-kDa BCGF activity with Tac antigen-inducing activity that also has a synergistic effect with IL-2 on normal B-cell proliferation.

Animals↗

Radiotherapy for carcinoma of the uterine cervix by remotely controlled afterloading intracavitary system with high-dose-rate.

Between January 1978 and June 1985 seventy-nine patients with carcinoma of the uterine cervix were treated by a remotely controlled afterloading system (RALS) with high-dose-rate irradiation following external beam therapy. It was given once a week with a dose per fraction of 6 Gy to point A, 3 to 6 times, using applicators equipped with 1 Ci 60Co bead in each ovoid and two 1 Ci 60Co beads in a tandem 1 cm apart. Five-year survival rates were 85, 68, and 51 percent in Stages I, II, and III, respectively. Recurrences were noted in 12 patients (20%) with a minimum follow-up of 2 years: 4 patients in the parametrium, 2 in the central area, 5 in both the parametrium and central areas, and 5 in the para-aortic lymph node. Complications were noted in 13 patients (22%): temporary rectal bleeding in 7, stenosis of the sigmoid in 2, recto-vaginal fistula in 1, ileo-sigmoidal fistula in 1, and perforation of the intestine in 2 patients. The treatment results of the high-dose-rate schedule for RALS appear to be comparable to those of conventional low-dose-rate systems reported by others. Therefore a fraction dose of 6 Gy to point A once a week by RALS should be considered to be practical, economical, and acceptable to patients.

Brachytherapy↗