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Biomedical subjects

I Morimoto

Publications and source records attributed to I Morimoto.

At least 73 records · Page 4Linked to original sources

Enhancing effect of interleukin-2 on production of parathyroid hormone-related protein by adult T-cell leukemia cells.

Leukemic cells from patients with adult T-cell leukemia (ATL) can produce a calcium-regulating protein, parathyroid hormone-related protein (PTHrP). Moreover, it has been reported that ATL cells produce some cytokines besides PTHrP and that these cells respond to the T-cell growth factors, interleukin-2 (IL-2) and interleukin-4 (IL-4). To elucidate whether PTHrP produced by ATL cells is regulated by IL-2 or IL-4, we investigated the in vitro effects of IL-2 and IL-4 on the release of PTHrP. IL-2 increased the release of PTHrP into the conditioned medium from leukemic cells in some, but not all, ATL patients; however, IL-4 did not affect the PTHrP release. PTHrP messenger RNA (mRNA) levels were increased in ATL cells cultured in the presence of IL-2. These data suggest that IL-2 plays a role in the regulation of hypercalcemia by enhancing the production of PTHrP in ATL patients.

Aged↗

Interleukin-4 induces proliferation of adult T-cell leukemia cells.

To evaluate the effect of IL-4 on the growth of leukemic cells from adult T-cell leukemia (ATL) patients (ATL cells) and determine whether the IL-4 autocrine mechanism is involved in the growth of ATL cells, we studied the proliferative response of ATL cells, from 11 patients, cultured in the presence or absence of IL-4 in vitro. Leukemic cells from 10 of the 11 patients examined proliferated in response to both IL-2 and IL-4 in a dose-dependent manner. The proliferative response to IL-4 was higher than that obtained with IL-2 in 8 patients. The expression of the IL-2 receptor (IL-2R) alpha alpha-chain in leukemic cells from some patients was also enhanced by IL-4. The IL-4 receptor was demonstrated by flow cytometry on the surface of ATL cells. Neither IL-4-induced proliferation of ATL cells nor IL-4-induced IL-2R expression on ATL cells was inhibited by anti-Tac or anti-IL-2 antibody and, therefore, these effects of IL-4 are considered independent of endogenous IL-2 activity. However, IL-2 and IL-4 were undetectable in the culture supernatants of ATL cells from any patient by enzyme-linked immunosorbent assay. Interferon-gamma (IFN-gamma) partially inhibited IL-2 or IL-4-induced proliferation of ATL cells. These results suggest that leukemic cells from ATL patients proliferate by an IL-2 or IL-4 paracrine mechanism in lymphoid tissue in vivo and that IFN-gamma inhibits IL-2- or IL-4-induced proliferation of ATL cells.

Aged↗

Autocrine stimulation of interleukin-1 in the growth of human thyroid carcinoma cell line NIM 1.

We reported first in this study that human thyroid cell line NIM 1 established from a patient with papillary adenocarcinoma of the thyroid associated with hypercalcemia and peripheral neutrocytosis produced interleukin (IL)-1 alpha and IL-1 beta in the culture supernatant and cell lysate as detected by murine thymocyte proliferative response and enzyme-linked immunosorbent assay. Production of IL-1 alpha and IL-1 beta was further confirmed by the demonstration of IL-1 alpha and IL-1 beta messenger ribonucleic acid expression with Northern blot hybridization analysis. The in vitro growth of NIM 1 cells was inhibited by the addition of anti-IL-1 alpha and IL-1 beta antibody. The growth of NIM 1 cells was further enhanced by the addition of recombinant human IL-1 alpha and IL-1 beta, whereas this enhancement was also inhibited by the addition of anti-IL-1 antibody. IL-1 receptors were expressed on NIM 1 cells. These results suggest that IL-1 plays a regulatory role in the growth of NIM 1 cells by an autocrine mechanism.

Adenocarcinoma↗

Angiotropic lymphoma of paranasal sinuses with initial symptoms of oculomotor nerve palsy.

A 78-year-old female was found to have angiotropic lymphoma, a rare fatal disease, with initial symptoms of oculomotor nerve palsy. A biopsy of the paranasal sinus mucosa showed that the small vessels were occupied by large mononuclear cells which upon immunohistochemical examination tested positive for pre B-cell markers. She felt a gradually increasing pain in her left thigh. Magnetic resonance imaging suggested the involvement of neoplastic cells in the left femoral bone marrow. Following chemotherapy treatment remission was achieved. Early diagnosis of angiotropic lymphoma appears very significant, as this disorder could be well controlled by systemic chemotherapy.

Aged↗

Enhancing effects of IL-2 on M-CSF production by human peripheral blood monocytes.

Monocytes have the capacity to produce granulopoietic factors such as M-CSF and G-CSF. Our findings here showed that interleukin-2 (IL-2), at a concentration of more than 0.05 ng/ml, led to a 12-fold increase in the production of M-CSF in the human peripheral blood mononuclear cells after 72 h incubation compared to the control culture. Even in purified monocyte cultures with added IL-2, a 3-fold increase in M-CSF production was observed at an IL-2 concentration of 50 ng/ml. The enhancing effect of IL-2 on M-CSF secretion was also observed when IL-2-stimulated non-phagocytic cell-conditioned medium was added to monocyte cultures. These results indicated that IL-2, both directly and indirectly, activated monocytes to enhance the production of M-CSF. In addition, the expression of IL-2 receptor (CD25) on monocytes was more enhanced in cultures containing IL-2 than in cultures without IL-2. On the other hand, IL-2 did not induce G-CSF production in purified monocytes. These in vitro results suggest that when IL-2 is used clinically, the various biological activities of M-CSF should also be taken into consideration.

Cells, Cultured↗

[Buddhist mummies in Japan].

The mummy of priest Kochi (preserved at Saishoji Temple, Teradomari, Niigata Pref.) has become famous, since it appeared in the book "Snow Country Tales" written by Bokushi Suzuki in 1841 (Fig. 1). In a country of high humidity, such as Japan, the belief that mummification could not, and did not, exist would not be altogether unfounded, but rather more a matter of common sense. There are two dozen Buddhist mummies in this country. It was not known until 1961 that a reliable source of artificial mummification has existed in Japan. The Japanese Buddhist mummies, apart from those of the Fujiwara family, a powerful clan of northeast Japan in the 12th century, dated mostly from the 17th to the 19th century as given in Table 1. Three principal types of mummification described by Vreeland, Jr. and Cockburn (1980) could be identified in the Japanese Buddhist mummies: type I, natural mummification; type II, intentional natural; and type III, artificial. Matsumoto (1990) classified the mummies into four groups, based on their ideological backgrounds: group A, mummies of the priests having faith in the Amitabha (the Supreme Buddha presiding over the Pure Land in the West); group B, sokushin-butsu mummies of the priests belonging to the Shingon sect of Japanese Buddhism founded by Kukai (Kobo-daishi); group C, nyujo mummies of the priests having faith in the Maitreya (the Buddha presiding over the Pure Land in the North, or the Buddha of the future); and group D, other mummies. These mummies of groups A, B, C and D are respectively listed in Table 2. Previous papers have shown that the mummies of the groups A, C and D belonged to the mummification of type I (natural mummification) or type II (intentional natural), whereas those of only the group B were of type III (artificial). The mummies of groups A to D were given as follows. a) Mummies of group A. The four mummies of the Fujiwara family in the Amitabha faith (preserved at Chusonji Temple, Hiraizumi, Iwate Pref.), which were laid in daisies for Buddhist images at golden Konjikido, a model of the Western Pure Land of Amitabha, did not bear any evidence of Ainu character in their physical traits. Of these, the mummy of Yasuhira Fujiwara, of which the head and neck were severely injured by swords, showed that it had been decapitated. This decapitated head had suffered mutilations: i.e. a long iron nail had been driven into the forehead, and the both auricles and the nose had been cut off.(ABSTRACT TRUNCATED AT 400 WORDS)

Buddhism↗

Inhibitory effects of endothelin-3 on vasopressin release from rat supraoptic nucleus in vitro.

Endothelin (ET) is thought to be involved in the central regulation of body water metabolism. A recent perfusion study of rat hypothalamus showed that ET has a direct stimulatory action on arginine-vasopressin (AVP) release. This study was undertaken to investigate whether ET acts directly on AVP release for supraoptic nucleus (SON) neurons, using brain slices containing only the SON. It was demonstrated that ET inhibited the AVP release dose-dependently from 10(-11) M to 10(-6) M. No difference of the effects of ET-1 and ET-3 on AVP release was observed. These results suggest that ET directly inhibits SON neurons through the ETB receptor.

Animals↗

Interactions between recombinant human erythropoietin and serum factor(s) on murine megakaryocyte colony formation.

We investigated the interactions between human erythropoietin (hEpo) and serum factor(s) on murine megakaryocyte (MK) colony formation. Serum-free cultures supported the growth of a large number of murine MK colonies in the presence of murine interleukin-3 (mIL-3). The addition of fetal calf serum (FCS) to mIL-3-containing cultures resulted in only a minimal increase in the number of murine MK colonies. In contrast, hEpo alone had no murine MK colony-stimulating activities in serum-free cultures. hEpo required the presence of FCS, murine serum, or human serum in cultures to promote murine MK colony growth and synergized with these sera to stimulate murine MK colony formation. Furthermore, sera from patients with aplastic anemia showed higher synergistic activities with hEpo than sera from hematologically normal persons (normal human serum). When normal human serum was fractionated by gel-filtration chromatography, two peaks with the synergistic activity were observed in the eluent. However, serum did not show any synergistic effects with hEpo on the growth of murine GM colonies or murine colony-forming unit-erythroid-derived colonies. Although human serum synergized with hEpo to stimulate murine MK colony formation, human cytokines such as IL-3, IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF) failed to induce murine MK colony formation in Epo-containing cultures. In cultures containing human IL-1 alpha + human IL-6 + hEpo as well as in cultures containing hEpo, human IL-3 and human GM-CSF failed to show stimulatory effects on murine MK colony formation. Moreover, the synergistic activity of human serum with hEpo could not be neutralized by antibodies such as antihuman IL-1 alpha, antihuman IL-3, antihuman IL-4, antihuman IL-6, antihuman G-CSF, and antihuman GM-CSF. Our data show that serum contains a growth factor(s) that synergizes with Epo to stimulate the proliferation and differentiation of MK precursors, and strongly suggest that this factor(s) is an unique growth factor(s) that is distinct from IL-1 alpha, IL-3, IL-4, IL-6, G-CSF, and GM-CSF.

Anemia, Aplastic↗

Dihydrotestosterone accumulation in genital skin fibroblasts derived from elderly men with prostatic hyperplasia.

The conversion of testosterone to dihydrotestosterone (DHT) by 5 alpha-reductase and the interconversion between DHT and 5 alpha-Androstane-3 alpha,17 beta-diol (3 alpha-diol) by 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) were studied in fibroblasts derived from the genital skin of 15 prepubertal boys (2-10 yr), 17 young men (20-40 yr), 13 elderly men (60-78 yr) without clinically evident prostatic pathology, and 17 elderly men (61-88 yr) with benign prostatic hyperplasia (BPH). Respective DHT formations from testosterone (5 alpha-reduction) and 3 alpha-diol (3 alpha-HSOR oxidation) were not different among genital skin fibroblasts of the 4 groups. However, DHT degradation to 3 alpha-diol (3 alpha-HSOR reduction) was significantly lower in fibroblasts from elderly men with BPH than in those from the prepubertal boys (P less than 0.01), the young men (P less than 0.01), and the elderly men without BPH (P less than 0.05). 3 beta-HSOR reduction in fibroblasts of the BPH group was significantly lower (P less than 0.05) than in those of the elderly men without BPH; however, it did not differ from values for the prepubertal boys and the young men. (3 alpha + 3 beta)-HSOR reduction was also significantly lower (P less than 0.05) in the BPH group than respective values of the three other groups. These results indicate that DHT accumulation may occur in genital skin fibroblasts from elderly men with BPH, resulting from a shift in the overall balance of androgen metabolism, which favors the net formation of DHT.

Aged↗

Clastogenicity of aporphine alkaloids in vitro.

The chromosomal aberration test using a Chinese hamster lung cell line (CHL) was carried out on 19 aporphine alkaloids including apomorphine with and without rat liver homogenates (S9) mix. Eighteen of 19 alkaloids tested induced chromosomal aberration in the presence or absence of S9 mix. Among the alkaloids tested, anolobine, liriodenine and 4,5-dioxodehydrocrebanine induced chromosomal aberrations at relatively low concentrations and as low as 2.5, 5 and 3.13 micrograms/ml, respectively. Dicentrine, anolobine and 4,5-dioxodehydrocrebanine induced chromosomal aberrations with high frequencies. Apomorphine induced 10% aberrant cells at 12.5 micrograms/ml in the direct method and 12% at 100 micrograms/ml with S9 mix in the S9 method. Liriodenine which was the most potent mutagen for TA100 with S9 mix and roemerine which was the most potent for TA98 with S9 mix in Ames test were also clastogenic with and without S9 mix.

Alkaloids↗

A kindred of multiple endocrine neoplasia type 2B.

We describe familial cases of multiple endocrine neoplasia (MEN) 2B: A 48-year-old man is the proband. He had pheochromocytoma, medullary thyroid carcinomas (MTCs), parathyroid hyperplasia, mucosal neuromas, eversion of eyelids and Marfanoid appearance, and then underwent adrenalectomy and total thyroidectomy. Family screening revealed that his two daughters (10 and 8 years old) had mucosal neuromas and increased serum calcitonin (CT). Both of them had MTCs but no pheochromocytoma, and their MTCs were surgically removed. The father and his children have been in favorable condition since the operations. Southern blot analysis with 33 polymorphic DNA probes was done in MTCs obtained from two daughters. An RBP3 (10q11.2) locus linked to a predisposing gene on chromosome 10 was uninformative in either patient because of constitutional homozygosity. Loss of heterozygosity at the MYCL1 locus on chromosome 1p32 was observed in MTC from the younger sister, but no loss of heterozygosity was recognized in other loci examined. Deletion of the 1p32 locus may play a role in the development of MEN 2B.

Adrenal Gland Neoplasms↗

Siblings of 21-hydroxylase deficiency (non-salt-losing) with aldosterone hypersecretion.

We describe siblings with the non-salt-losing form of 21-hydroxylase deficiency who had hypersecretion of aldosterone and plasma renin activity (PRA). Blood pressure and serum electrolytes in both cases were normal despite the aldosterone hypersecretion. Aldosterone secretion was elevated markedly with ACTH administration and with sodium deprivation and/or volume depletion during ACTH suppression by dexamethasone. With suppression by dexamethasone, aldosterone hypersecretion was decreased with lowering of the steroids proximal to the block in the biosynthetic pathway. However, urinary sodium excretion was decreased. These results suggest that the biosynthetic pathway for aldosterone production was preserved. Furthermore, aldosterone hypersecretion and high PRA may serve to compensate for the sodium loss which results in turn from the overproduction of the sodium-losing steroids, such as progesterone and 17 alpha-hydroxyprogesterone which are aldosterone antagonists.

Adolescent↗

Variability of origin of serratus anterior muscle in Japanese.

The observations on 567 male and 251 female Japanese cadavers revealed that there was a wide variation of the lowermost origin of the serratus anterior muscle ranging from the 6th to the 12th rib. The most frequent cases in males were of the 8th rib type (42.5%), whereas those in females were of the 9th rib type (43.3%). There was a statistically significant difference in the distribution of the muscle origin between the sexes. The observations also showed that bilateral symmetry of the muscle origin was preponderant over asymmetry, the symmetric cases forming about seven-tenths of all individuals without sex distinction.

Asian People↗

[Adult T-cell leukemia with cervical bone tumor showing immunophenotypic change].

A 60-year-old man born in Miyazaki prefecture was admitted to our hospital complaining of skin rash in December 1989. On hematological examinations, leukocyte count was 14,200/microliters with 49% of abnormal lymphocytes showing lobulated nuclei. The surface marker study revealed their phenotype as CD4+8-. Anti human T cell leukemia virus type I (HTLV-I) antibody and monoclonal integration of proviral DNA were positive. From the above results, he was diagnosed as adult T-cell leukemia (ATL). Abnormal lymphocytes gradually decreased without treatment after the first admission. In January, 1990, he began to complain of neck pain. Two months later he was readmitted because of paresis of extremities and disturbance of urination. Vertebral bone mass and a compressed spinal cord in the 4th cervic level were confirmed by MR imaging. He received a resection of tumor and an anterior fusion of vertebrae. The bone tumor was histologically diagnosed as malignant lymphoma, diffuse medium-size cell type and the infiltrating cells had their phenotype as CD4+8+. He was postoperatively treated with combination chemotherapies, but neurological abnormalities did not improve. He died of pneumonia on 35 days after the operation. A postmortem examination revealed extradural tumor formation with ATL cells. This case is considered to be rare in respect of both the disappearance of most peripheral abnormal lymphocytes without any treatments and the cervical bone tumor showing immunophenotypic change.

CD4 Antigens↗

[Lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) therapy that improved lymphadenopathy in a patient with B cell non-Hodgkin's lymphoma].

A 70-year-old man was admitted to our hospital on March 9, 1989 because of fever, superficial generalized lymphadenopathy, upper abdominal mass and right pleural effusion. The diagnosis of non-Hodgkin's lymphoma (follicular medium sized cell type, B cell) was made by a biopsy of the neck lymph node. Peripheral blood mononuclear cells were obtained from the patient by cytopheresis. The cells were cultured for 8 days with interleukin-2 (IL-2) to generate Lymphokine-activated killer (LAK) cells. The patient received a total of 7.7 x 10(9) LAK cells intravenously over a period of 3 weeks. He also received continuous intravenous infusion of IL-2 for 17 days, starting 2 days before the first infusion of LAK cells. After this therapy, although his superficial generalized lymphadenopathy disappeared or decreased in size, the size of the upper abdominal mass did not decrease. Therefore, it is suggested that adoptive immunotherapy is a beneficial treatments for B cell lymphoma. However, LAK cells should be generated in much larger quantities for a more successful therapeutic result.

Aged↗

Effect of hyperbaric oxygenation on macrophage function in mice.

Hyperbaric oxygenation (HBO) has an immunosuppressive effect. The possible mechanisms of this immunosuppressive effect were assessed by determining the production of interleukin-1 (IL-1), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), as well as phagocytosis by splenic macrophages from HBO-treated mice. Although HBO treatment did not have any significant effect on IL-6 production and phagocytotic activity, a marked decrease in IL-1 production and a significant decrease in PGE2 production were observed. These results suggest that the reduction of IL-1 production may play an important role in the immunosuppressive effect of HBO.

Animals↗

DHT formation and degradation in cultured human skin fibroblasts: DHT accumulation in the genital skin.

The conversion of testosterone to dihydrotestosterone (DHT) by 5 alpha-reductase and the interconversion between DHT and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) by 3 alpha-hydroxy-steroid oxidoreductase (3 alpha-HSOR) were studied in fibroblasts derived from the genital skin of 22 males and 6 females, and from the nongenital skin of 19 males and 9 females with normal gonadal function. The formation of DHT from testosterone (5 alpha-reduction) was significantly greater in fibroblasts from genital skin than in those from nongenital skin in both males (2.15 +/- 1.43 vs 0.81 +/- 0.46 pmol/mg protein/h, mean +/- SD, P less than 0.001) and females (2.52 +/- 1.99 vs 0.69 +/- 0.18, P less than 0.01). Furthermore, DHT formation from 3 alpha-diol (3 alpha-HSOR oxidation) was also significantly greater in genital skin fibroblasts than in nongenital skin fibroblasts of males (5.47 +/- 3.37 vs 2.52 +/- 1.74 pmol/mg protein/h, P less than 0.01). However, the degradation of DHT to 3 alpha- and/or 3 beta-diol (3 alpha- and/or 3 beta-HSOR reductions) was not different between genital and nongenital skin fibroblasts of either males or females. Respective ratios of DHT formation to DHT degradation (5 alpha-reduction/3 alpha-HSOR reduction, 3 alpha-HSOR oxidation/3 alpha-HSOR reduction) were also significantly greater (P less than 0.002) in genital skin fibroblasts than in nongenital skin fibroblasts of males. On the other hand, both DHT formation and degradation were not different between male and female genital skin fibroblasts. These results suggest that the increased production of DHT in genital compared to nongenital skin results from increased 5 alpha-reduction and 3 alpha-HSOR oxidation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗