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Biomedical subjects

M Kawakami

Publications and source records attributed to M Kawakami.

At least 307 records · Page 17Linked to original sources
PubMed1992

Autostimulatory effects of IL-6 on excessive B cell differentiation in patients with systemic lupus erythematosus: analysis of IL-6 production and IL-6R expression.

Introducing avidin-biotin complex ELISA for anti-DNA antibody, the mechanism of in vitro production of anti-ssDNA antibody as well as of polyclonal immunoglobulin mediated by an IL-6-IL-6R loop was studied in patients with systemic lupus erythematosus (SLE). Regardless of the presence or absence of T cells, B cells from SLE patients could produce IgG anti-ssDNA antibody as well as total IgG without any stimulation. Low density B cells obtained by Percoll gradient density centrifugation responded to rIL-6 to produce IgG and IgG anti-ssDNA antibody. rIL-2 and rIL-4 had lesser effects on the differentiation of low density B cells. In fact, IL-6R was preferentially expressed on low density B cells from active SLE patients, as detected by anti-IL-6R MoAb, MT18, which did not inhibit IL-6 binding. SLE B cells, especially high density B cells, produced greater amounts of IL-6 in culture supernatants than did T cells, regardless of whether disease was active or inactive. Normal T cells and B cells did not produce significant amounts of IL-6. Thus, endogenous IL-6 produced by high density B cells bound to the IL-6R preferentially expressed on the low density B cells, and drove them into terminal differentiation, especially in active SLE patients. Further, addition of polyclonal anti-IL-6 or anti-IL-6R MoAb (PM1), which inhibited IL-6 binding, both inhibited IgG anti-ssDNA antibody as well as total IgG production by SLE B cells in a dose-dependent manner. These results suggest that interruption of the autocrine IL-6 loop would be of therapeutic value in SLE.

Antibodies, Antinuclear↗
PubMed1992

Siblings with normal LDL receptor activity and severe hypercholesterolemia.

We report about a brother and sister having clinical symptoms similar to those of homozygous familial hypercholesterolemia (FH) but surprisingly who have normal low density lipoprotein (LDL) receptor activities (M. Harada-Shiba et al, J Jpn Atheroscler Soc 1991; 19:227-242). The LDL receptor activities in the cultured fibroblasts of the patients were compared with those of FH heterozygotes and homozygotes for the LDL receptor mutation. The LDL receptor activities in the cultured fibroblasts of the patients were in the normal range, but their plasma cholesterol concentrations were similar to patients with homozygous FH. After the plasma LDL was removed by plasmapheresis in both patients, plasma cholesterol levels started to increase. The "rebound" of plasma cholesterol was compared with those for heterozygous and homozygous FH. The plasma cholesterol levels of the patients, which were greater than 410 mg/dl 2 weeks after plasmapheresis, were much higher than those of FH heterozygotes (232-311 mg/dl) but similar to those of FH homozygotes (345-464 mg/dl). The urinary mevalonate excretion rate, which reflects the rate of whole-body cholesterol synthesis, was higher for the brother (patient 1, 32.6 nmol/kg.day-1) than for the normal subjects (17.7 +/- 4.1 nmol/kg.day-1) but was similar to those of FH homozygotes (31.2 +/- 4.3 nmol/kg.day-1) and heterozygotes (29.8 +/- 10.9 nmol/kg.day-1). To estimate the catabolic and production rates of cholesterol in the brother, the time course for the increment in the total cholesterol level after plasmapheresis was analyzed by the two-compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

The effect of local application of 1,25-dihydroxycholecalciferol on osteoclast numbers in orthodontically treated rats.

Orthodontic tooth movement requires remodeling of periodontal tissues, especially alveolar bone. 1,25-(OH)2D3, the active form of vitamin D3, is known to be a potent stimulator of osteoclastic bone resorption. The purpose of this study was to investigate the effect of local application of 1,25-(OH)2D3 on osteoclast numbers induced by experimental tooth movement. A piece of orthodontic elastic band was inserted between the first and second upper molars of male Wistar rats weighing about 200 g each. Twenty microL of 1,25-(OH)2D3 (10(-12)-10(-7) mol/L) was injected locally into the submucosal palatal area of the root bifurcation of the right first molar. The left side was injected with phosphate-buffered saline (PBS). The number of osteoclasts was counted in a 700 x 1050 microns 2 area of the interradicular septum. The local injection of 1,25-(OH)2D3 caused a dose-dependent increase in osteoclast number. The effect of 1,25-(OH)2D3 reached a response plateau at 10(-10) mol/L when greater than a three-fold rise in osteoclast number was attained compared with the PBS-treated controls. While the insertion of a piece of elastic band for three days induced a significant increase in osteoclasts in the alveolar bone, daily injections of 20 microL of 10(-10) mol/M 1,25-(OH)2D3 for three days markedly stimulated the numbers of osteoclasts induced by the insertion of an elastic band. 1,25-(OH)2D3 was apparently synergistic with mechanical stimuli, resulting in enhancement of the numbers of osteoclasts induced by mechanical stimuli alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Process↗
PubMed1992

Effect of age on the rate of tooth movement in combination with local use of 1,25(OH)2D3 and mechanical force in the rat.

The purpose of this study was to compare the amount and rate of tooth movement in young and mature rats administered 1,25(OH)2D3 simultaneous with application of mechanical force. In 30 seven-week-old and 30 28-week-old male Wistar rats, the right maxillary first molar was moved buccally with a fixed appliance. The appliances delivered forces ranging from 5 to 20 g. Twenty microL of 1,25(OH)2D3 (10(-10) and 10(-8) mol/L) was injected locally into the submucosal palatal area of the root bifurcation of the right first molar. The left side was injected with phosphate-buffered saline (PBS). In young rats receiving 10(-10) mol/L 1,25(OH)2D3 every three days, tooth movement significantly increased to 126% of that in PBS-injected control rats on day 20. In 1,25(OH)2D3-injected mature rats, tooth movement was stimulated markedly and increased with 10(-10) mol/L to 245% and with 10(-8) mol/L to 154% of the amount of tooth movement seen in the PBS-injected controls by the end of the experiment. PBS-injected rats had a plateau stage where tooth movement did not occur at all, while there was no such lag-time in the 1,25(OH)2D3-injected group which showed continuous tooth movement. The local injection of 1,25(OH)2D3 did not change serum calcium, phosphate, and alkaline phosphatase activity, and there were no apparent clinical or microscopic side-effects.

Activator Appliances↗
PubMed1992

Effect of a pulsing electromagnetic field on demineralized bone-matrix-induced bone formation in a bony defect in the premaxilla of rats.

A 2-mm non-healing bony defect was prepared in the premaxilla of male Wistar rats weighing about 180 g as a simulation of an alveolar cleft, for determination of whether a pulsing electromagnetic field (PEMF) could promote regeneration of bone induced by demineralized bone matrix (DBM). The defect was either treated with 7 mg DBM or was left as a non-grafted control. The rats were exposed to a PEMF with a frequency of 100 Hz, a 10-ms-wide burst with 100 microseconds-wide quasi-rectangular pulses, repeating at 15 Hz, and magnetic field strength of 1.5-1.8 G. Alkaline phosphatase activity increased significantly from day 7 in the DBM-graft-plus-PEMF group and from day 10 in the DBM-graft group, reaching a maximum on day 14. A greater-than-two-fold rise in alkaline phosphatase activity and a three-fold rise in the amount of 45Ca incorporation in the DBM-graft-plus-PEMF group were attained compared with those of the DBM-graft group. The DBM-graft-plus-PEMF group produced more bone with almost complete osseous bridging in the defect sites than did the group treated with DBM only on day 35. The findings indicate that PEMF had an enhancing effect on the bone-inductive properties of the DBM through the stimulation of osteoblast differentiation induced by DBM.

Alkaline Phosphatase↗
PubMed1992

Fluorescent probe-labeled lipid microsphere uptake by human endothelial cells: a flow cytometric study.

Lipid microspheres have been used as carriers of drugs such as prostaglandin E1 (lipo-PGE1) and corticosteroid (liposteroid). Lipo-PGE1 is used for the treatment of chronic arterial occlusive diseases because its activity is far greater than that of free PGE1 in vivo. To verify the fact that the drug carriers, lipid microspheres, are preferentially taken up by endothelial cells, we labeled lipid microspheres with a fluorescent probe, DiI (DiI-LM), and observed them in some in vitro models. Stoichiometric fluorescence was obtainable, and the fluorescence was stable between pH 3.3 and pH 8.9. Human umbilical vein endothelial cells and cells of a human endothelial cell line, ECV304, showed increased uptake of DiI-LM, 81% and 61%, respectively. In contrast, uptakes were less than 7% in human skin fibroblasts, 3T3 cells, and human neutrophils. Prominent perinuclear fluorescence was also observed in endothelial cells by fluorescence microscopy. DiI-LM and flow cytometric analysis will be useful for studies to elucidate the precise mechanism of the selective accumulation of lipid microspheres by cells in blood vessel walls.

Carbocyanines↗
PubMed1992

Atrial natriuretic peptide in eel plasma, heart and brain characterized by homologous radioimmunoassay.

A highly specific and sensitive radioimmunoassay has been developed for the measurement of eel atrial natriuretic peptide (ANP). The antiserum, raised against eel ANP-(1-27) did not cross-react with two other eel natriuretic peptides, i.e. eel ventricular natriuretic peptide and C-type natriuretic peptide (CNP), or with any mammalian ANPs, CNPs or brain natriuretic peptides so far identified. The minimal detectable amount was 0.39 fmol (0.90 pg)/tube with more than 99% confidence. Because of its high sensitivity, the radioimmunoassay makes it possible to measure eel ANP directly with only a few microlitres of plasma without extraction. Using the radioimmunoassay we found high levels of ANP in the atrium (11 +/- 2 pmol/mg wet tissue, n = 8), and much lower levels in the ventricle (56 +/- 8 fmol/mg, n = 8) and the brain (22 +/- 1 fmol/mg, n = 8) of eels. Eel plasma contained a large amount of ANP (247 +/- 66 fmol/ml, n = 8) compared with the levels reported in mammals, although atrial levels are similar between eels and mammals. Gel-permeation chromography revealed that a major form of ANP stored in the eel atrium, ventricle and brain has a molecular mass of approximately 14 kDa but low molecular forms of about 3 kDa are predominant in eel plasma. A detailed analysis with reverse-phase high-performance liquid chromatography showed that a major molecular form circulating in eel plasma is ANP-(1-27). ANP-(1-27) was also detected in small amounts in the eel atrium, ventricle and brain.

Amino Acid Sequence↗
PubMed1992

The effect of batroxobin on cochlear blood flow.

Cochlear blood flow is considered to be closely related to cochlear function. Among several etiologic factors implicated in inner ear diseases, disturbance of local blood flow is held to be one of the most important. With this in view, various pharmaceuticals are currently being used to increase local blood flow in patients with inner ear diseases. In the control of blood flow there are three major factors; systemic blood pressure (perfusion pressure), vascular tone, and blood viscosity. Batroxobin (BX) was developed to increase local blood flow by lowering blood viscosity through defibrinogenation; it is used in the treatment of thrombosis and occasionally for the treatment of sudden deafness. In the present study, we observed the effect of BX on cochlear blood flow in guinea pigs, using a laser Doppler flowmeter, and measured the blood fibrinogen concentration after BX infusion. There was an obvious increase in cochlear blood flow during the observation period of 3 h after 10 BU/kg were infused, and a slight increase when 2 BU/kg were infused. Blood fibrinogen levels decreased dramatically by 30 min after BX infusion (10 BU/kg), and the extremely low level attained was maintained throughout the 3-h observation period. Hemorrhage from the surgically opened ear was noted in 2 animals during the experiment and rectal bleeding in one.

Animals↗
PubMed1992

[MR study of the brain stem in elderly subjects].

Findings in patients in whom brain stem lesions were suspected were studied by a high-field-strength (1.5 T) MR imager. MR scans were obtained in 97 patients over a 10-month period. The mean age was 71 years (range, 39-94 years). A high incidence of infarction and lesions showing a high signal on T2-weighted image, but an almost normal signal on the T1-weighted image were observed at the pons in elderly cases. Furthermore, cases in which these two findings were observed, had a high incidence of lesion at other regions than pons. Cases with a past history of hypertension had higher incidence of lesions at the pons than normotensive patients (alpha less than 0.01). These findings suggest that MRI examination in the elderly could detect a high incidence abnormal lesions at the brain stem as well as in basal ganglia.

Aged↗
PubMed1992

Role of monocyte colony-stimulating factor in foam cell generation.

Recently, we reported that human monocyte colony-stimulating factor (M-CSF) stimulates the clearance of lipoproteins containing apoB100 via both low density lipoprotein receptor-dependent and -independent pathways in target cells of M-CSF, and reduces plasma cholesterol level (Journal of Biological Chemistry, 265:12869-12875, 1990). This suggests a linkage of cytokines to the metabolic regulation of plasma cholesterol. Furthermore, we found a significant role of M-CSF in cholesterol metabolism of human monocyte-derived macrophages. M-CSF enhanced not only the uptake of acetylated low density lipoprotein and oxidized low density lipoprotein in macrophages, but also the efflux of cholesterol from cholesterol-loaded macrophages. To elucidate in vivo effects of M-CSF on cholesterol efflux from tissues, we administered an intravenous injection of 3H-cholesterol (150 microCi) into WHHL rabbits 1 month before starting M-CSF treatment. We observed an increased cholesterol efflux from tissues to plasma high density lipoprotein after M-CSF treatment when cholesterol efflux was estimated as the change in specific radioactivity of plasma high density lipoprotein-cholesterol. This result suggests that M-CSF can enhance the excretion of cholesterol from target cells of M-CSF, such as cholesterol-loaded macrophages in the arterial wall, and reduce the rate of atherogenesis.

Cells, Cultured↗
PubMed1992

Tensile adhesion evaluation in a new universal test.

A tensile testing jig was designed to test adhesion between various materials and tooth surfaces, and between materials of various consistencies, modes of setting and properties. This study examined the adhesion of both flowable and condensable, light cured and chemically cured, direct and indirect restorative materials to dentin. All materials were mixed and placed according to manufacturer's directions. The bonds were tested in tension after 24 hours. The substrate was dentin, except in group 1. Results in MPa +/- SD: 1. Photobond & Photoposterior to enamel 15.84 +/- 3.93; 2. Superbond C&B and metal inlay 6.20 +/- 3.00; 3. SuperBond C&B and amalgam 5.76 +/- 1.89; 4. All-Bond and metal inlay 4.46 +/- 1.16; 5. Mirage Bond and Newbond and amalgam 2.97 +/- 0.85; 6. Vitrebond 2.06 +/- 0.95; 7. Newbond and amalgam 1.70 +/- 0.61; 8. Ketac-Bond 0.73 +/- 0.40. The groups (2,3,4), (4,5), (5,6,7) and (6,7,8) were not significantly different at the 95% confidence level, calculated by the Student-Newman-Keuls test. The testing method was useful for all materials studied.

Adhesives↗
PubMed1992

Cytokine regulation of prolyl 4-hydroxylase production in skin fibroblast cultures from patients with systemic sclerosis: contribution to collagen synthesis and fibrosis.

Prolyl 4-hydroxylase (PH) is an enzyme that catalyzes an essential step in procollagen synthesis. PH production, as measured by the new ELISA method, was significantly higher in fibroblast cultures from patients with systemic sclerosis (SSc; N = 7) than in cultures from healthy controls (NC; N = 5) (p less than 0.01). Transforming growth factor-beta and tumor necrosis factor-alpha significantly increased PH production, but recombinant interferon-gamma had a significant negative effect on PH production. Since the production of PH is relevant to collagen synthesis by fibroblasts of patients with SSc, regulation of PH production may have therapeutic value.

Cells, Cultured↗
PubMed1992

Plasma thrombomodulin and alpha 2-plasmin inhibitor-plasmin complex are elevated in active systemic lupus erythematosus.

Plasma levels of thrombomodulin and alpha 2-plasmin inhibitor-plasmin complex were measured by ELISA in patients with rheumatic diseases. Thrombomodulin levels in patients with active systemic lupus erythematosus (SLE) were significantly higher than those in patients with inactive SLE or in healthy controls. This suggests that thrombomodulin, normally a component of vascular endothelial cell membrane, is easily released to plasma in patients with active SLE. High titers of the thrombomodulin level and the correlated alpha 2-plasmin inhibitor-plasmin complex elevations imply vascular injury, and consequently, excessive fibrinolytic processes in active SLE.

Adolescent↗
PubMed1992

Effect of prolyl 4-hydroxylase inhibitor on fibroblast collagen production in vitro: an approach to the treatment of systemic sclerosis.

Prolyl 4-hydroxylase (PH), which catalyzes the conversion of prolyl residues to 4-hydroxyproline, plays a central role in the synthesis and secretion of collagen. We demonstrated that fibroblasts from patients with systemic sclerosis produced significantly more PH than those from healthy subjects. To regulate excessive collagen production by scleroderma fibroblasts, we examined the effect of a PH inhibitor on collagen production by scleroderma fibroblasts. Fibrostatin-C, a PH inhibitor, significantly decreased the amount of procollagen (type I) production by scleroderma fibroblasts (p < 0.01). We suggest that this PH inhibitor might be a valid antifibrotic agent useful for the treatment of patients with scleroderma.

Blotting, Northern↗
PubMed1992

[An autopsy case of malignant rheumatoid arthritis (MRA) which was difficult to distinguish from polyarteritis nodosa (PN)].

We encountered a patient who was diagnosed as rheumatoid arthritis (RA) at 15 years old and developed malignant RA (MRA) within one year. He suffered from mononeuritis multiplex and cutaneous infarction. Despite of treatment including steroid pulse therapy, neuritis progressed. Lung infiltration, pancreatitis and intestinal bleeding were accompanied. He died of disseminated intravascular coagulation on 153 days after admission. Autopsy revealed systemic rheumatoid vasculitis in coronary artery, pancreas, liver, small and large intestine, kidney and lung. These severe vasculitis occurred in young RA patient are rare case and it is important to consider the therapy and prognosis.

Adolescent↗
PubMed1992

Concentrations and molecular forms of C-type natriuretic peptide in brain and cerebrospinal fluid.

To develop a radioimmunoassay (RIA) specific for human C-type natriuretic peptide (hCNP), we used a highly specific antiserum raised in rabbits. Quantitative inhibition tests with various natriuretic peptides demonstrated that the 50% inhibitory dose of hCNP was 15 fmol, whereas those of other natriuretic peptides were 10(5)-fold higher, indicating a specificity satisfactory for determining concentrations of hCNP in tissues. Using this antiserum, we detected immunoreactive hCNP (ir-hCNP) in various regions of human brain and spinal cord, as well as in cerebrospinal fluid (CSF). The ir-hCNP concentrations in human neural tissues were approximately 10-fold higher than those of immunoreactive human atrial natriuretic peptide (ir-hANP). The mean (+/- SD) concentration of ir-hCNP (72.0 +/- 17.8 ng/L) in CSF also was 10-fold higher than that of ir-hANP (5.2 +/- 2.1 ng/L). Using gel-permeation chromatography, we identified two molecular forms of ir-hCNP in brain and CSF: a 2-kDa form corresponding to mature hCNP, which is composed of 22 amino acid residues (hCNP-22), and a 5- to 6-kDa form corresponding to an N-terminally extended molecule (hCNP-53). The latter form was predominant in brain; the former was the main constituent of hCNP in CSF. These results support the hypothesis that hCNP is a major natriuretic peptide, is synthesized in human brain, and functions in human central nervous tissues.

Aged↗