Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

At least 253 records · Page 14Linked to original sources

PubMed1994

Levels of hepatocyte growth factor in synovial fluid and serum of patients with rheumatoid arthritis and release of hepatocyte growth factor by rheumatoid synovial fluid cells.

OBJECTIVE: To determine the levels of hepatocyte growth factor (HGF) in synovial fluids (SF) and sera from patients with rheumatoid arthritis (RA); to examine how these correlate with several disease variables in patients with RA and with levels of interleukin-6 (IL-6) in SF of these patients; and to examine whether HGF is released from adherent synovial cells (ASC) and synovial fluid cells (SF cells). METHODS: An enzyme linked immunosorbent assay was used to measure levels of HGF and IL-6. SF samples were obtained from 22 patients with RA, 12 with osteoarthritis (OA), and one with septic arthritis. Serum samples were collected from 40 patients with RA. HGF levels in culture supernatants from ASC and SF cells were measured. RESULTS: The mean values of HGF in SF were 1.21 ng/ml for patients with RA, 0.19 ng/ml for those with OA and 0.18 ng/ml for the one with septic arthritis. HGF levels in SF of patients with RA were significantly higher than of those with OA (p < 0.01). The levels for patients with RA correlated with the serum C-reactive protein concentrations (r = 0.626, p < 0.01) and IL-6 levels in SF (r = 0.476, p < 0.05). The mean value of HGF in sera from patients with RA was 0.28 ng/ml. HGF levels in SF were higher than those in sera drawn simultaneously from the same patients with RA. In vitro, release of HGF from rheumatoid ASC was not detected. However, SF cells from patients with RA released HGF spontaneously. CONCLUSION: Our observations suggest that HGF in SF of patients with RA is produced by SF cells and is related to disease activity of RA, and thus that HGF may play a role in RA.

Adult↗

PubMed1994

A case of temporary severe disequilibrium hypercalcemia.

We report a rare case of temporary and severe hypercalcemia: the patient, a 69-year-old woman, was admitted to Osaka City University Hospital on July 25, 1992, for severe hypercalcemia. The laboratory data on admission revealed severe hypercalcemia (14.9 mg/dl) and renal dysfunction with increased serum creatinine level (2.9 mg/dl). The urinary excretion of pyridinoline and deoxypyridinoline was increased, and serum levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D were decreased. The data suggested that increased bone resorption was a probable main factor in the development of the hypercalcemia. The development of hypercalcemia seemed to be of acute onset because of (1) her severe symptoms caused by hypercalcemia and (2) impaired renal function which was improved after normalization of serum calcium level. Combination therapy with saline infusion and furosemide was administered, and there was a gradual decrease and subsequent normalization of serum calcium level along with serum creatinine. Even 8 months after discontinuation of the therapy for hypercalcemia, the serum calcium level remained within the normal range. The measured values of serum factors which are suspected to have a hypercalcemic effect, such as PTH, parathyroid hormone-related peptide and the cytokines (interleukin-1 alpha, interleukin-1 beta, interleukin-2, interleukin-6 and tumor necrosis factor-alpha) were all within the normal range. In summary, the hypercalcemia in this patient was regarded to be a type of disequilibrium hypercalcemia due to a combination of increased bone resorption and decreased renal capacity to excrete calcium. Furthermore, since it was temporary and did not recur even in the absence of treatment, the hypercalcemia was concluded to have developed due to an imbalance in calcium regulation rather than as a result of organic disease.

Aged↗

PubMed1994

Flow cytometric analysis of cell-killing actions of 5-fluorouracil in human colorectal cancer cells.

To confirm our previous kinetic analysis of the mode of cell-killing action of 5-fluorouracil (5-FU), we carried out a flow cytometric analysis with human colorectal cancer DLD-1 cells. Cells were treated with each cytotoxic concentration of 5-FU for 1 or 72 h, and the periodic changes in flow cytometric pattern were compared with those of 5-fluorouridine (FUrd) and 5-fluoro-2'-deoxyuridine (FdUrd). When cells were cultured with 5-FU for 72 h, most of them accumulated in S phase and remained there. This pattern was the same as that seen in cells that were continuously exposed to FdUrd. In contrast, when cells were exposed to 5-FU for 1 h and cultured in drug-free medium, they ended the cell-cycle traverse in either G2/M or G1 phase after an immediate but transient accumulation in S phase. Results were identical to those observed with cells similarly treated with FUrd. These results demonstrated a good accordance with those of our kinetic analysis, and strongly suggested that the mode of cell-killing exhibited by 5-FU differs with exposure time: 5-FU acts like FUrd in short exposure conditions, and it acts similarly to FdUrd in continuous exposure conditions.

Cell Cycle↗

PubMed1994

[Recent advances and problems in peripheral arterial reconstruction].

Recent advances in the field of peripheral arterial reconstruction have been remarkable. These advances are mainly derived from the development of diagnostic technology such as Doppler ultrasound analysis, further refinement of surgical technique including surgical instruments and materials, and naturally improvement of patient care in the pre-, peri- and postoperative period. During the past 14 years we have performed peripheral arterial reconstruction in 1,200 cases (1,660 limbs) mainly with occlusive lesion due to arteriosclerosis obliterans. In our hand, aorto-iliac occlusive lesion has been routinely bypassed with Dacron prostheses and the secondary patency rate at eleven years reached 96.5%. The main problems encountered in this region were anastomotic aneurysm in the femoral artery (3.9%) and graft infection (1.2%). In the infrainguinal region there are still problems to be solved, although the primary (secondary) 5 year patency rates of reversed vein graft as well as in situ vein graft including femoro-popliteal below knee and femoro-crural bypasses have exceeded 70% (85%). First, there is no graft material comparable to the autogenous vein (AVG). Secondly, many of the AVG should suffer occlusive pathological changes from the environment in the long term following surgery. At the present time, we have no effective method to solve these problems, therefore we should follow up the patients heedfully to maintain the graft patency as well as to improve their quality of life and prognosis.

Anastomosis, Surgical↗

PubMed1994

[A case report of innominate and carotid artery aneurysms causing cerebral embolism].

Brachiocephalic aneurysms are relatively rare in Japan. A case with tandem aneurysms of innominate and right carotid artery was experienced and its successful surgical treatment was reported. A 54-year-old female patient had an attack of cerebral infarction with left hemiparesis. Computed tomography and angiogram revealed aneurysms of innominate and right carotid artery causing cerebral embolisms. Aneurysmectomy and replacement with Dacron prosthesis was performed. A temporary shunt was utilized between ascending aorta and common carotid artery during clamping carotid artery. She had no problems after operation, and her postoperative course was uneventful.

Anastomosis, Surgical↗

PubMed1994

[Cerebral cysticercosis treated with praziquantel--a case report].

We report a patient with cerebral cysticercosis treated with praziquantel. The patient, a 30-year-old man, was admitted to our hospital with a 12-year-history of generalized convulsion. MRI of the brain showed multiple cysts and the largest one in the right frontal lobe measured 3 cm in diameter. The intensity of cyst contents was same as that of the CSF on T1- and T2-weighted images. X-Ray of extremities and blood examinations showed no abnormal findings. The immunological testing for cysticercosis was negative in the serum. An operation was performed for the largest cyst in the right frontal lobe. The cyst was pathologically confirmed as cysticercosis. He was treated with praziquantel 50 mg/kg body weight in 3 divided doses per day with steroid cover for 7 days. The same therapy was repeated at an interval of 14 days. The patient was suffering from headache and scintilating scotoma only for a few days during the therapy. MRI revealed reduction in the size of the cysts in the right occipital lobe but no change in the other cysts. He was given praziquantel 600 mg per day for two months. As a result, the cysts in the right occipital lobe disappeared and the other cysts diminished on MRI.

Adult↗

PubMed1994

Mechanism of hemolysis of canine erythrocytes induced by L-sorbose.

The cause of species difference in the susceptibility of erythrocytes to L-sorbose, and the difference in the hemolytic effect of sorbose on high potassium-containing (HK) and low potassium-containing (LK) canine erythrocytes were examined. L-Sorbose was phosphorylated in canine erythrocytes, but not in human erythrocytes. Furthermore, sorbose-1-phosphate, a metabolite of L-sorbose, strongly inhibited the hexokinase of LK canine erythrocytes, but not that of HK canine erythrocytes. These results strongly indicated that inhibition of hexokinase by sorbose-1-phosphate in LK erythrocytes induced severe glycolytic limitation in these cells, resulting in hemolysis, and that HK erythrocytes are resistant to sorbose-induced hemolysis because these cells have a high hexokinase activity.

Animals↗

PubMed1993

Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo.

Dendritic cells, while effective in sensitizing T cells to several different antigens, show little or no phagocytic activity. To the extent that endocytosis is required for antigen processing and presentation, it is not evident how dendritic cells would present particle-associated peptides. Evidence has now been obtained showing that progenitors to dendritic cells can internalize particles, including Bacillus Calmette-Guerin (BCG) mycobacteria. The particulates are applied for 20 h to bone marrow cultures that have been stimulated with granulocyte/macrophage colony-stimulating factor (GM-CSF) to induce aggregates of growing dendritic cells. Cells within these aggregates are clearly phagocytic. If the developing cultures are exposed to particles, washed, and "chased" for 2 d, the number of major histocompatibility complex class II-rich dendritic cells increases substantially and at least 50% contain internalized mycobacteria or latex particles. The mycobacteria-laden, newly developed dendritic cells are much more potent in presenting antigens to primed T cells than corresponding cultures of mature dendritic cells that are exposed to a pulse of organisms. A similar situation exists when the BCG-charged dendritic cells are injected into the footpad or blood stream of naive mice. Those dendritic cells that have phagocytosed organisms induce the strongest T cell responses to mycobacterial antigens in draining lymph node and spleen. The administration of antigens to GM-CSF-induced, developing dendritic cells (by increasing both antigen uptake and cell numbers) will facilitate the use of these antigen-presenting cells for active immunization in situ.

Animals↗

PubMed1993

Regulation of release of hepatocyte growth factor from human promyelocytic leukemia cells, HL-60, by 1,25-dihydroxyvitamin D3, 12-O-tetradecanoylphorbol 13-acetate, and dibutyryl cyclic adenosine monophosphate.

Hepatocyte growth factor (HGF) secreted from human promyelocytic leukemia cell line, HL-60, is indistinguishable from HGF in human plasma and its release is significantly stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), a differentiation-inducer of HL-60 cells into monocytes/macrophages (Nishino T et al: Biochem Biophys Res Commun 181:323, 1991). TPA stimulated HGF release from the cells through an activation of C-kinase, but not through a formation of reactive oxygen species. Furthermore, dibutyryl cAMP (dbcAMP), an activator of A-kinase and granulocyte-inducer, also stimulated HGF release. 1,25-Dihydroxyvitamin D3, another monocyte/macrophage-inducer, abated either TPA- or dbcAMP-stimulated synthesis and release of HGF in a dose-dependent manner probably via its nuclear receptor as reflected by vitamin D analog study. The effects of these three reagents on the steady-state levels of HGF mRNA of 6.0 kb corresponded with their effects on its protein levels. Furthermore, a close correlation between intracellular and extracellular HGF levels strongly suggested that these reagents affected HGF release mainly on its synthesis step. Recombinant human HGF significantly stimulated the proliferation and alkaline phosphatase activity of mouse osteoblastic cell line, MC3T3-E1. In summary, HL-60 cells secrete HGF, whose synthesis is specifically regulated by various reagents independent of their differentiation-inducing effects. Because HGF shows a direct effect on osteoblast-like cells, it might be involved in the interaction of bone marrow cells with bone cells.

Alkaline Phosphatase↗

PubMed1993

[Iodination and binding characteristics of 125I-d(CH2)5 [Tyr(Me)2, Tyr(NH2)9] AVP].

With iodinated vasopressin analogue, d(CH2)5[Tyr(Me)2, Tyr(NH2)9] AVP, at position 9, followed by purification by HPLC (specific activity 473-543Ci/mmol), a specific binding was observed in the rat liver plasma membrane fraction. Scatchard analysis indicated a single class of high-affinity binding sites with a Kd of 0.23nM and Bmax of 142fmol/mg protein. V2-agonist, DDAVP, did not displace 125I-vasopressin analogue. These results suggest that 125I-d(CH2)5[Tyr(Me)2, Tyr(NH2)9] AVP with a high specific activity is a useful tool to investigate V1-receptors.

Animals↗

PubMed1993

Effect of substituting fluorine for hydrogen at C-26 and C-27 on the side chain of 1,25-dihydroxyvitamin D3.

Previous reports have demonstrated that introduction of fluorine atoms at C-26 and C-27 of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) results in the potentiation of various aspects of some biological activities. The higher biological activities of 26,26,26,27,27,27-hexafluoro- 1,25-dihydroxyvitamin D3 (26,27-F6-1,25-(OH)2D3) were accounted for in part by a decrease in metabolic inactivation via the 26- and 27-hydroxylation pathways. In addition to 26,27-F6-1,25-(OH)2D3 not being hydroxylated in the 26 and 27 positions, it did not undergo 24-hydroxylation despite a significant induction by 26,27-F6-1,25-(OH)2D3 of 24-hydroxylase activity in the HL-60 cell system. Another fluorinated vitamin D3 analog, 26,26,26,27,27,27-hexafluoro-1 alpha-hydroxyvitamin D3 (26,27-F6-1 alpha-OH-D3) may not undergo 25-hydroxylation as efficiently as 1 alpha-OH-D3 in vivo because a rise in serum 26,27-F6-1,25-(OH)2D3 levels after injection of 26,27-F6-1 alpha-OH-D3 was delayed significantly with a much smaller amplitude. Furthermore, 26,26,26,27,27,27-hexafluoro-1,23(S),25-trihydroxyvitamin D3 retained full activity in the induction of HL-60 cell differentiation even after 23(S)-hydroxylation, in contrast to 1,23(S),25-(OH)3D3. These data suggested that substitution of fluorines for hydrogens at C-26 and at C-27 positions may result in alteration in chemical reactivity and/or conformation of C-23, C-24 and C-25 positions of the 1,25-(OH)2D3 molecule.

Animals↗

PubMed1993

Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow.

The developmental origin of dendritic cells, a specialized system of major histocompatibility complex (MHC) class II-rich antigen-presenting cells for T-cell immunity and tolerance, is not well characterized. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate dendritic cells, including growth and development from MHC class II-negative precursors in suspension cultures of mouse bone marrow. Here we studied colony formation in semi-solid methylcellulose cultures, a classical bioassay system in which GM-CSF induces the formation of mixed granulocyte-macrophage colonies. When colonies were induced from MHC class II-negative precursors, a small subset (1-2%) of typical dendritic cells developed alongside macrophages and granulocytes. The dendritic cells were distinguished by their cytologic features, high levels of MHC class II products, and distinct intracellular granule antigens. By using differential adherence to plastic, enriched populations of the various myeloid cell types were isolated from colonies. Only the dendritic cells stimulated a primary T-cell immune response, the mixed leukocyte reaction, and the potency was comparable to typical dendritic cells isolated from spleen. Macrophages from mixed or pure colonies were inactive as stimulator cells. Therefore, three distinct pathways of myeloid development--granulocytes, macrophages, and dendritic cells--can develop from a common MHC class II-negative progenitor under the aegis of GM-CSF.

Animals↗

PubMed1993

Effects of intrathymic injection of organ-specific autoantigens, parietal cells, at the neonatal stage on autoreactive effector and suppressor T cell precursors.

Thymectomy on day 3 after birth (3d-Tx) induces autoimmune gastritis (AIG) in 81%, and oophoritis (AIO) in 25% of BALB/c mice at the age of 2 to 3 months. Intrathymic, but not intraperitoneal injection of syngeneic parietal cells into sex-matched BALB/c mice within 24 h of birth resulted in almost complete prevention of the development of AIG in these mice in which 3d-Tx was performed. The prevention induced was parietal cell specific, since the development of AIO was not inhibited in female mice. Moreover, the injection of BALB/c liver cells, Mls-matched (BALB/c) and -disparate (DBA/2) B blasts which resulted in V beta 6 T cell deletion, as well as the injection of staphylococcal enterotoxin B failed to prevent the diseases. These findings suggested that recognition of an autoantigen in the thymus is necessary for the induction of tolerance, and that involvement of Mls-1 antigens in the pathogenesis of AIG, as has been suggested previously (Schwartz, R. H., Cell 1989. 57: 1073), was unlikely. T cells that suppress the development of organ-specific autoimmune diseases in 3d-Tx mice seem to maintain the unresponsiveness of autoreactive T cells at the periphery in normal mice. In agreement with our previous observations, we found that intraperitoneal (i.p.) injection of spleen cells from 3-month-old normal mice into 3d-Tx mice on day 10 after birth prevented the development of AIG, whereas spleen cells from age-matched AIG+ (mice with AIG) or AIG- (mice without AIG) 3d-Tx mice failed to do this. This implies that the suppressor cells probably affect the differentiation of effector-precursor to effector. In fact, these suppressor cells did not inhibit the adoptive transfer of AIG to nu/nu BALB/c mice by spleen cells from 3d-Tx mice manifesting AIG. By negative selection using monoclonal antibody and complement, it was confirmed that the phenotype of the suppressor cell was CD4. In contrast to 3d-Tx, 10d-Tx did not induce AIG, indicating the peripheralization of the suppressor cell by that time. On the other hand, intrathymic injection of parietal cells immediately after birth did not affect suppressor cell generation, implying that some T cells, including suppressor cells, escape thymus selection. We postulate that these cells correspond to the precursors of the autoreactive effector T cells and suppressor T cells that are present in normal mice.

Animals↗

PubMed1993

Comparison of uptake of mitomycin C and KW-2149 by murine P388 leukemia cells sensitive or resistant to mitomycin C.

KW-2149, a new mitomycin C (MMC) derivative, inhibited the growth of murine P388 leukemia in vitro at 20-fold lower concentrations than those of MMC. KW-2149 was also effective in inhibiting the growth of MMC-resistant P388 (P388/MMC) cells. To elucidate these characteristics of KW-2149, its uptake and efflux were compared with those of MMC in MMC-sensitive and -resistant P388 cells. Both MMC and KW-2149 accumulated rapidly in P388 cells after incubation at the concentration of 0.47 and 0.024 microM, respectively, which were the IC50 values at 1-h exposure. Although this concentration of KW-2149 was 20 times lower than that of MMC, its intracellular concentration was little more than that of MMC, suggesting that KW-2149 accumulated in the cells quite efficiently. The accumulated KW-2149 in the cells after 1-h treatment remained for as long as 24 h after the incubation of the cells in drug-free medium, suggesting that most of the intracellular KW-2149 or MMC was bound to cellular components. The ratios of resistance of P388/MMC cells to MMC and KW-2149 were 34 and 8.8, respectively, at 1-h exposure, suggesting that P388/MMC cells were partially resistant to KW-2149 in vitro. P388/MMC cells also showed partial resistance to cisplatin, Adriamycin, m-AMSA, and etoposide. The accumulation of MMC in P388/MMC cells was lower than that in P388 cells, although the size of the former cells was almost equal to that of the latter. As a result, the amount of DNA-bound MMC was lower in P388/MMC cells than in P388 cells, suggesting its involvement in the mechanisms of MMC resistance in P388/MMC cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

Erythrocyte ALA-d activity in experimentally lead-poisoned ducks and its change during treatment with disodium calcium EDTA.

To determine useful procedures for the diagnosis and prognosis of lead poisoning in waterfowl caused by ingestion of lead pellets, erythrocyte delta-aminolevulinic acid dehydratase (ALA-d) was investigated in experimentally lead-poisoned ducks. A highly positive correlation was observed between the concentration of blood lead and the ALA-d activity ratio (the ratio of activated:non-activated enzyme activity) in those birds given seven lead pellets (3 mm diameter). The ALA-d activity ratio rapidly increased after the administration of lead pellets, but began to fall immediately after the initiation of disodium calcium ethylenediamine tetra-acetate (CaEDTA) therapy which resulted in a rapid decrease in the concentration of lead in the blood of these birds. In contrast, the ALA-d activity remained inhibited even after blood lead levels began to decrease following treatment. These results demonstrated that the ALA-d activity ratio is a very useful and sensitive indicator for the diagnosis and evaluation of therapeutic effects after lead poisoning in waterfowl.

Animals↗

PubMed1993

Analyses of thymic abnormalities in autoimmune-prone (NZW x BXSB) F1 mice.

Thymic abnormalities of autoimmune-prone (NZW x BXSB)F1 mice are investigated. After the onset of autoimmune diseases, severe thymic atrophy is observed. The atrophied thymus shows lower CD4+ CD8+ T cell and higher CD4+CD8- or CD4-CD8+ T cell counts than aged-matched normal strains or other autoimmune-prone (NZB x NZW)F1(B/WF1) mice; even at the age of 40 weeks, B/WF1 mice have a large number of double-positive cells and a small number of single-positive cells. Thymocytes in the atrophic thymus of (NZW x BXSB)F1 mice respond better than normal mice to T cell-mitogens (PHA and ConA). In addition, the single-positive T cells are J-11d-negative. These findings indicate that the atrophic thymus includes mature T cells and a large number of plasma cells and B cells; it therefore responds well to lipopolysaccharides. Experiments in reciprocal transplantation of the thymus and bone marrow between (NZW x BXSB)F1 and normal mice show that the thymic abnormalities are due to defects of the hemopoietic stem cells (HSCs) rather than either intrinsic abnormalities in the thymus or extrinsic abnormalities such as anti-thymus antibodies. It should be noted that the atrophic thymus recovers after transplantation of normal bone marrow cells; the atrophic thymus still has the capacity to induce the differentiation of normal T cells (including double-positive T cells) if normal HSCs are introduced.

Aging↗

PubMed1993

Analyses of origin of synovial cells and repairing mechanisms of arthritis by allogeneic bone marrow transplantation.

MRL/lpr mice spontaneously develop rheumatoid arthritis (RA)-like disease. Recently we have observed that bone marrow transplantation (BMT) with bone graft to recruit donor stromal cells can be used to treat autoimmune diseases (including RA-like lesions) in MRL/lpr mice. In this paper, we characterize the origin of synovial cells with the use of radiation chimeras and elucidate the repairing mechanism of RA by BMT. Type A synoviocytes have been thought to play an important role in the initiation of inflamed synovia, since a large number of Type A synoviocytes have been seen in inflamed synovia of both RA patients and MRL/lpr mice. Using [C57BL/6JJic-bg-->MRL/lpr] chimeric mice, we found Type A synoviocytes to be derived from donor bone marrow cells. They appeared in the inflamed synovia 4 weeks after BMT. However, at this time, the repairing process was not prominent. Serial biopsy studies revealed that newly developed T cells with normal functions play a more crucial role in the treatment of RA in MRL/lpr mice than do Type A synoviocytes.

Animals↗

PubMed1993

Effect of aminohydroxypropylidene diphosphonate on the bone metabolism of patients with parathyroid adenoma.

Aminohydroxypropylidene diphosphonate (APD), a potent inhibitor of bone resorption, is used to control hypercalcemia in various diseases. It is less effective, however, in the management of hypercalcemia induced by primary hyperparathyroidism. We investigated the effect of APD on the bone metabolism of five patients with parathyroid adenoma. Before parathyroidectomy, 30 mg of APD was administered intravenously. Serum calcium decreased in all cases one to two days after APD administration, although it did not decrease to the normal range. Serum phosphorus also decreased. Urine calcium and hydroxyproline excretion, markers of osteoclasts activity, decreased dramatically. Serum alkaline phosphatase (ALP) and osteocalcin, markers of osteoblast activity, decreased after APD administration. Serum intact parathyroid hormone (PTH) and 1,25-dihydroxy-vitamin D (1,25[OH]2D) increased. These results indicate that APD is partially effective in the management of preoperative serum calcium level in patients with parathyroid adenoma. As osteoclasts activity is inhibited by APD, osteoblasts activity is also suppressed. Elevation of PTH and 1,25(OH)2D after APD-induced decrease in serum calcium level may explain the partial and limited effect of APD on lowering serum calcium in patients with parathyroid adenoma.

Adenoma↗