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M Inaba

Publications and source records attributed to M Inaba.

At least 163 records · Page 9Linked to original sources
PubMed1997

Induction of c-kit molecules on human CD34+/c-kit < low cells: evidence for CD34+/c-kit < low cells as primitive hematopoietic stem cells.

c-kit, a receptor for stem cell factor, has been widely accepted as a distinctive marker for hematopoietic stem cells. However, the level of c-kit expression on pluripotent hematopoietic stem cells is still controversial in mice and humans. We purified CD34+/c-kit < low cells (phenotypically c-kit-negative but only detectable at the message level) from human cord blood and examined their maturational steps in relation to the expression of c-kit molecules. When the CD34+/c-kit < low cells were cultured with cytokines (flt 3 ligand, interleukin 6 and interleukin 7) plus immobilized anti-CD34 monoclonal antibody (to crosslink CD34 molecules), c-kit molecules were clearly induced within 24 h. The c-kit expression gradually increased until day 8. When CD34+/c-kit(low) or CD34+/c-kit+ cells that had been induced from CD34+/c-kit < low cells were resorted and recultured using a methylcellulose culture system, they showed the same colony-forming ability as the freshly isolated CD34+/c-kit(low) or CD34+/c-kit+ cells, respectively. Furthermore, CD34+/c-kit < low cells have a similar hematopoietic potential to CD34+/c-kit(low) cells in assays for long-term culture initiating cell and colony-forming unit culture generated from long-term cultures. These findings suggest that CD34+/c-kit < low cells mature into CD34+/c-kit(low) and CD34+/c-kit+ cells, and acquire the reactivity to various humoral hematopoietic stimuli. Moreover, CD34+/c-kit < low cells showed a low level of rhodamine 123 retention, suggesting that CD34+/c-kit < low cells have multidrug resistance. Therefore, the CD34+/c-kit < low cells without colony-forming unit-granulocyte-erythroid-macrophage-megakaryocyte activity are also a pluripotent hematopoietic stem cell population, and the expression of c-kit on c-kit < low cells is the first maturational step of hematopoiesis.

Antigens, CD34↗
PubMed1997

Intrathymically injected hemopoietic stem cells can differentiate into all lineage cells in the thymus: differences between c-kit+ cells and c-kit < low cells.

To investigate whether hemopoietic stem cells (HSCs) can differentiate into all lineage cells even in the thymus, we injected two types of HSCs (c-kit+ and c-kit < low cells) obtained from C57BL/6 Ly5.1 mice directly into the thymus of 7.5 Gy-irradiated C57BL/6 Ly5.2 mice. When c-kit < low cells (low density/lineage-/CD71-/major histocompatibility complex class I high/Sca-1+/Thy-1low/ c-kit < low) were injected, donor-derived (Ly5.1) cells were detected on day 8 after intrathymic (i.t.) injection, and the number reached a maximum on day 24 after injection. Granulocytes and macrophages were also detected on day 8 after injection. However, B220+ B cells were observed on day 13. Eighteen days after i.t. injection, the injected lobes showed red color due to the synchronous development of erythroid cells. Histological studies revealed the development not only of erythroid lineage cells but also of megakaryocytes in the thymus. In contrast, when c-kit+ cells were injected, a significant number of donor-derived cells were detected on day 5 after i.t. injection (three days earlier than in the case of c-kit < low cell injection). The differentiation into erythroid lineage cells was also observed six days earlier than when c-kit < low HSCs were injected. These findings suggest that c-kit < low HSCs are more primitive than c-kit+ HSCs, although both can differentiate into all lineage cells after i.t. injection.

Animals↗
PubMed1997

Requirement of major histocompatibility complex-compatible microenvironment for spleen colony formation (CFU-S on day 12 but not on day 8).

To clarify major histocompatibility complex (MHC) restriction between hematopoietic stem cells (HSCs) and microenvironments, T cell-depleted bone marrow cells (BMCs) were transplanted into MHC-compatible and MHC-incompatible recipients. A significantly larger number of spleen colony-forming units (CFU-S) on day 12 were noted in MHC-compatible recipients, while only a small number were observed in MHC-incompatible recipients. There was, however, no significant difference in CFU-S counts on day 8 between the two groups. A large number of CFU-S counts on day 12 were also observed in F1 hybrid recipients, as seen in syngeneic recipients. The decrease in CFU-S counts on day 12 in MHC-incompatible recipients was also observed even after in vivo abrogation of T and NK cells. The difference in CFU-S counts on day 12 became more prominent when HSC-enriched cells were transferred. These results suggest that an MHC restriction exists between pluripotent HSCs (P-HSCs) and spleen microenvironments. Furthermore, experiments using B10. A recombinant strains revealed that H-2D and S loci play a crucial role in the MHC restriction. The experiments of serial transplantation suggest that the differentiation and proliferation of P-HSCs are inhibited in MHC-incompatible microenvironments. It is therefore likely that the MHC-compatible microenvironment is essential to the differentiation and proliferation of P-HSCs.

Animals↗
PubMed1997

Positive correlation between levels of IL-1 or IL-2 and 1,25(OH)2D/25-OH-D ratio in synovial fluid of patients with rheumatoid arthritis.

The present study determined the levels in synovial fluid (SF) of vitamin D metabolites (1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D (24,25(OH)2D) and 25-hydroxyvitamin D (25-OH-D)), and of the cytokines. We evaluated SF from 21 patients with rheumatoid arthritis (RA) and 6 patients with osteoarthritis (OA). The levels of vitamin D metabolites in SF, as determined by two different extraction methods, were significantly correlated (p < 0.05, n=7). The levels of 3 vitamin D metabolites were significantly higher in the RA SF than in OA SF (p < 0.05). The ratio of 1,25(OH)2D/25-OH-D in RA SF, which is presumed to reflect the activity of 25-OH-D-1-hydroxylase (1-OH-ase), was positively correlated with the levels of interleukin-1alpha (IL-1alpha), IL-1beta, and IL-2 in such SF, and was significantly higher than that in sera from RA patients. This suggests an important role for these cytokines in the activation of 1-OH-ase in RA synovium. The ratio of 24,25(OH)2D/25-OH-D, which is presumed to reflect 25-OH-D-24-hydroxylase (24-OH-ase) activity, was significantly correlated with 1,25(OH)2D levels only in RA SF, but not in sera from RA patients, suggesting a local regulation of vitamin D metabolism that 1,25-(OH)2D induces 24-OH-ase as in other target cells. Our observations suggested that 1,25(OH)2D and 24,25(OH)2D are produced locally from 25-OH-D in RA synovium, and that the syntheses of 1,25(OH)2D and 24,25(OH)2D may be affected by IL-1/IL-2 and 1,25(OH)2D in RA SF, respectively.

Arthritis, Rheumatoid↗
PubMed1997

Insulin resistance in non-obese, non-insulin-dependent diabetic patients with diabetic nephropathy.

To investigate the association between insulin resistance and diabetic nephropathy, peripheral insulin sensitivity indices (M/I values) were evaluated via euglycemic-hyperinsulinemic clamp in 45 non-obese, non-insulin-dependent diabetic (NIDDM) subjects. The patients were divided into four groups: 18 with normoalbuminuria (urinary albumin excretion rate [AER] < 30 mg/24 h, stage I), 10 with microalbuminuria (30 < or = AER < or = 300 mg/24 h, stage II), seven with overt proteinuria (AER > 300 mg/24 h, stage III), and 10 with uremia (serum creatinine levels > 2.0 mg/dL, stage IV). There were no significant differences in age, body mass index (BMI), fasting plasma glucose, or hemoglobin A1c (HbA1c) among the four groups. No significant difference in M/I values was seen between stage I and stage II (6.30 +/- 0.73 and 5.95 +/- 0.85 mg/kg/(min per microU/mL) x 100, respectively). M/I values in the stage I and stage II groups were strongly correlated with BMI (r = -.790, P = .0001 and r = -.785, P = .007, respectively). M/I values in the stage III group (4.53 +/- 0.51) were lower than in the stage I group, although not significantly so. M/I values in the stage IV group (3.16 +/- 0.37) were significantly lower than in the stage I group (P = .025). In multiple regression analysis with a model in which age, sex, BMI, HbA1c, and creatinine clearance (Ccr) were included as independent variables, BMI and Ccr were demonstrated to be significant and independent contributors to insulin sensitivity indices as the dependent variable (beta = -0.716 and beta = 0.272, respectively, R2 = .564, P < .0001). In conclusion, the present cross-sectional study demonstrated in non-obese NIDDM patients with nephropathy that microalbuminuria did not affect peripheral insulin resistance, but uremia did, as in nondiabetic patients, and that the peripheral insulin resistance was significantly contributed to by the degree of obesity and uremia.

Adult↗
PubMed1997

Role of infrainguinal bypass in Buerger's disease: an eighteen-year experience.

OBJECTIVES: The role of bypass to the distal arteries for patients with Buerger's disease (thromboangiitis or TAO) remains controversial because of the high incidence of graft failure. We retrospectively reviewed the results of 71 bypasses to evaluate their efficacy. MATERIALS AND METHODS: We performed 71 autogenous vein bypasses in 61 patients with TAO. Of the patients, 97% were heavy smokers. The indications for surgery were claudication in 41%, and ischaemic ulcer or gangrene in 59%. Of the bypasses 85% were to the crural arteries or to the arteries below the ankle. The grafts used were 53 single saphenous veins, and 18 venovenous composite grafts. RESULTS: There were 38 graft failures, the main causes including anastomosis to a diseased artery, disease progression (which occurred in smokers after surgery), and vein graft stenosis. Of 38, 10 were restored to patency by revision surgery. Primary and secondary patency rates were 48.8% and 62.5% at 5 years, and 43.0% and 56.3% at 10 years, respectively. The patency rates of the postoperative non-smoking group was significantly higher than that of the smoking group (66.8% vs. 34.7%, p < 0.05). Thirty-six patients (59%) had successful revascularisation and returned to full-time work. However, of 28 with secondary failure, 11 underwent amputation, while 14 had persistent disabling claudication. CONCLUSION: Bypass to the distal arteries is an effective treatment for TAO patients, and the long-term patency is quite satisfactory as long as patients stop smoking.

Adult↗
PubMed1997

Intrarenal hemodynamic abnormalities in diabetic nephropathy measured by duplex Doppler sonography.

Intrarenal hemodynamics were studied by duplex Doppler sonography in 112 inpatients with type II diabetes mellitus (DM; 65 males, 47 females, 58 +/- 13 years old). The resistive index (RI) and pulsatility index (PI) of the interlobar arteries were calculated. The patients were divided into four groups: group I consisted of patients with urinary albumin excretion (UAE) < 20 micrograms/min (N = 42), group II with 20 < or = UAE < 200 (N = 28), group III with UAE > or = 200 (N = 25), and group IV with serum creatinine > or = 1.5 mg/dl (N = 17). Both RI and PI values in groups II, III, and IV were significantly higher than those in the controls (age- and sex-matched healthy persons, N = 37; P < 0.001), and those in group IV were significantly higher than those in groups I, II, and III (P < 0.0001). Multiple regression analysis revealed that RI values in DM patients were significantly affected by creatinine clearance, age, and duration of diabetes (R2 = 0.554, P < 0.0001). When intima-medial thickness (IMT) of the femoral and carotid arteries were measured by B-mode ultrasonography, RI values were significantly correlated with both the femoral and carotid arterial IMT. These results demonstrate that intrarenal hemodynamic abnormalities are present in type II DM patients with nephropathy, and that intrarenal hemodynamics are affected by decreased glomerular function and also probably by advanced arteriosclerosis.

Aged↗
PubMed1997

Structure of the TCR expressed on a gastritogenic T cell clone, II-6, and frequent appearance of similar clonotypes in mice bearing autoimmune gastritis.

A parietal cell-specific Th1 clone, II-6, which was established from a BALB/c mouse bearing post-thymectomy autoimmune gastritis (AIG), recognizes a peptide of the alpha subunit (alpha891-905) of H+/K+-ATPase and induces gastritis in nu/nu BALB/c mice by adoptive cell transfer. In the present study, the primary structure of the TCR of II-6 was determined as Valpha10-Jalpha c5a-Calpha and Vbeta14-Jbeta2.3-Cbeta2 by cDNA cloning. Using PCR with specific primers, we defined the use of this II-6 TCR in nu/nu mice with transferred II-6 cells and in mice that spontaneously developed AIG by thymectomy on day 3 after birth (d3-Tx). II-6 TCR mRNAs were detected in the gastric mucosa of all of the nu/nu mice, suggesting that II-6 cells indeed home to the gastric mucosa and thereby were directly involved in the destruction of target parietal cells. TCR beta chain mRNAs encoding CDR3 region sequences almost identical with that of II-6 were also found in the gastric mucosa in 43% (six of 14 mice tested) of the d3-Tx AIG mice at 4-12 weeks old by nested RT-PCR. Such a frequent appearance of similar clonotypes in independent individuals suggests that T cells bearing II-6-like TCR including the II-6 itself might be directly involved in, although not essential for, the pathogenesis of AIG in 3d-Tx mice.

Amino Acid Sequence↗
PubMed1997

Myristoyl gelatin as a sealant for Dacron vascular prostheses.

Myristoyl gelatin (MG) retains its gel structure at temperatures above body temperature without any crosslinking. As a coating material, MG adheres well to polyester fibers, and the outermost layers of the sealant that are in contact with blood or surrounding tissue become hydrophilic. We produced MG-impregnated knitted Dacron vascular prostheses (MG graft [MGG]) and investigated the usefulness of MG as a sealant by replacing the thoracic aorta of dogs. MGGs (5 cm long with an inner diameter of 10 mm) were implanted in 5 mongrel dogs (10-20 kg), and the grafts were retrieved at intervals of 4 h and 2, 4, 8, and 15 weeks after grafting. There was no thrombus formation on the flow surface of the MGGs, indicating adequate antithrombogenic properties. No resorption of MG occurred until after 2 weeks, and neither immune reaction nor excessive foreign body reaction was noted. Fragmentation of the sealant induced by cell infiltration began to occur at 4 weeks, yet the sealing effect persisted. The organization of MGG was almost complete at 8 weeks. Because of its pliability and effective adhesion to polyester fibers, its antithrombogenicity, and the persistent sealing effect due to delayed biodegradation and resorption, we conclude that MG is an extremely useful sealant for polyester vascular prostheses.

Animals↗
PubMed1997

Thrombopoietin inhibits in vitro osteoclastogenesis from murine bone marrow cells.

To determine whether thrombopoietin (TPO) can modulate the osteoclastic differentiation from hematopoietic stem cells, we investigated the effect of TPO on in vitro osteoclastogenesis by using the coculture of murine bone marrow cells with the stromal cell line (ST2) in the presence of 1alpha,25-dihydroxyvitamin D3 and dexamethasone. Recombinant human TPO inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated cells in a dose-dependent manner (0.02-200 ng/ml). The effect of TPO on differentiation of bone-resorbing capacity was investigated by pit assay. TPO dose dependently decreased the areas oftoluidine blue-stained resorption pits (2.0-200 ng/ml). To identify the cellular target of TPO, we used a variety of bone marrow/stromal cell coculture methods. Initially, we found that TPO mainly exerted its effect on the early stage of osteoclastic differentiation in delayed addition experiments. Consequently, the majority of TPO's inhibition of osteoclastic cell formation was due to its effect on bone marrow cells. Finally, we examined whether transforming growth factor-beta (TGFbeta) and platelet-derived growth factor (PDGF), major cytokines produced by megakaryocytes, mediate the inhibitory effect of TPO. The addition of either anti-TGFbeta or anti-PDGF antibody to bone marrow cell culture completely antagonized the effect of TPO on osteoclastogenesis. Furthermore, treatment of bone marrow cells with TGFbeta or PDGF mimicked the inhibitory effect of TPO. These data suggest that TPO inhibits osteoclastogenesis through stimulating thrombopoiesis and that TGFbeta and PDGF mediate the effect of TPO by impacting on macrophage-lineage cells as osteoclast precursors.

Analysis of Variance↗
PubMed1997

Glucose intolerance in spontaneously hypertensive and Wistar-Kyoto rats: enhanced gene expression and synthesis of skeletal muscle glucose transporter 4.

To clarify the relationship between blood pressure and insulin resistance, we studied the role of glucose transporter 4 (GLUT4) in skeletal muscle and the effect of angiotensin-converting enzyme inhibitor on insulin resistance. Blood pressure and plasma glucose and plasma insulin responses to glucose loading (2 g/kg, i.p.) were measured in spontaneously hypertensive rats (SHRs), Wistar-Kyoto rats (WKYs), and Wistar rats at 8, 12, and 20 wk of age. GLUT4 gene expression and plasma membrane protein content were also determined in the gastrocnemius muscle. SHRs and WKYs at the age of 8 wk had significantly higher plasma glucose levels than did age-matched control Wistar rats. Insulin response also tended to be higher. Glucose intolerance was also present in 12-wk-old SHRs, but normalized at the age of 20 wk. In contrast, WKYs were glucose intolerant at 12 and 20 wk. Gene expression and plasma membrane content of GLUT4 were augmented in both 8-wk-old SHRs and WKYs, indicating a compensatory increase in these variables. Effects of captopril (20-30 mg/kg/d from 8 to 20 wk) on GLUT4 were also investigated in these three strains. Captopril improved steady state plasma glucose levels in association with 1.2- to 2.5-fold higher GLUT4 gene expression and a 1.4-fold increase in skeletal muscle GLUT4 protein in SHRs and WKYs. Our results suggest that (1) not only SHRs but also WKYs may have glucose intolerance and hence insulin resistance; (2) gene expression and protein synthesis of skeletal muscle GLUT4 are probably increased compensatorily, indicating that abnormalities in GLUT4 do not have a pivotal role in the development of insulin resistance in SHRs and WKYs; and (3) captopril stimulates skeletal muscle gene expression and synthesis of GLUT4, providing further evidence of its beneficial effect on glucose metabolism.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effects of epidermal growth factor on maternal and fetal serum amino acid levels in rats.

Pregnant rats were subcutaneously administered with mouse epidermal growth factor (EGF) at the concentration of 0, 100, or 200 micrograms/kg body weight/day from day 18 to 21 of gestation. The amino acid analysis by high-performance liquid chromatography demonstrated that the umbilical venous/maternal and fetal/maternal ratio of serum proline concentration increased in EGF dose-dependent manner accompanied by the increase in the ratios of total fetal weight and placental weight to maternal body weight gain. These results suggested that EGF regulates fetal growth by, as one of its possible mechanism, promoting placental proline supply from mother to fetus.

Amino Acids↗
PubMed1997

Apolipoprotein B (apoB) concentrations in lipoproteins in cows.

The concentrations of apolipoprotein B (apoB)-48 and apoB-100 in triglyceride-rich lipoproteins (TRL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) fractions separated by gel permeation chromatography were determined in Holstein and Japanese black cows by enzyme-linked immunosorbent assay (ELISA). A significant correlation (p < 0.01) was observed between apoB-48 in TRL and plasma triglyceride (TG) levels in both Holstein and Japanese black cows. Additionally, apoB-48 in TRL and plasma TG levels in Holstein cows were significantly lower (p < 0.01) than those in Japanese black cows. These results suggested that TG derived from intestinal (exogenous) TRL rather than from liver (endogenous) TRL was the major source of milk fat.

Animals↗
PubMed1997

Relationship between gastric emptying and an alpha-glucosidase inhibitor effect on postprandial hyperglycemia in NIDDM patients.

OBJECTIVE: The purpose of the study was to examine the relationship between gastric emptying and the efficacy of an alpha-glucosidase inhibitor in NIDDM patients. RESEARCH DESIGN AND METHODS: Sixteen NIDDM patients (4 patients treated with diet therapy alone and 12 receiving a sulfonylurea) were given 0.6 mg of voglibose daily for 4 weeks. The efficacy of voglibose was assessed by measurement of HbA1c, fasting plasma glucose, and 45- and 120-min postprandial plasma glucose (PPG) and serum insulin concentrations before and after the 4 weeks of voglibose therapy. Gastric emptying was evaluated using the proportional cumulative area under the absorption curve (% AUC) of plasma acetaminophen concentration at 60 min after ingestion of a liquid test meal containing 20 mg/kg of acetaminophen. These measurements were also taken before and after the therapy. RESULTS: The change in the 45-min PPG levels from the fasting state correlated significantly with the % AUC of the plasma acetaminophen concentrations (r = 0.625, P = 0.0096) before the voglibose administrations. The mean 45-min and 2-h PPG levels were reduced significantly after 4 weeks of voglibose (P < 0.05 and P < 0.01, respectively). Two-hour postprandial serum insulin concentrations were also significantly reduced at the end of the treatment period (P < 0.05). The changes in the PPG levels between pre- and posttreatment periods correlated significantly with the % AUC of the plasma acetaminophen concentrations before the treatment period (r = 0.499, P = 0.0490; r = 0.713, P = 0.0019, respectively). There was no significant difference in the plasma acetaminophen concentrations between pre- and posttreatment periods. CONCLUSIONS: The rate of gastric emptying affects the efficacy of voglibose therapy in NIDDM patients. Voglibose did not however alter the rate of gastric emptying.

Acetaminophen↗
PubMed1997

Gastric myoelectrical activity in patients with diabetes. Role of glucose control and autonomic nerve function.

OBJECTIVE: Gastric myoelectrical activity was studied in diabetic patients using electrogastrography (EGG) to elucidate the relationship between glucose control, diabetic autonomic neuropathy (AN), and gastrointestinal motility. RESEARCH DESIGN AND METHODS: Cutaneous EGG was recorded during 1 h of fasting and 1 h after the ingestion of a standard meal in 57 diabetic patients and 10 healthy subjects. EGG was measured in 12 diabetic patients after glycemic control for 4 weeks. Diabetic patients were also studied with respect to the presence of gastrointestinal symptoms and AN. RESULTS: The percentage of dominant electrical frequency (DF) in normal range (the percentage ratio between the power at 2.4-3.6 cycles/min [cpm] and at 1-10 cpm) was significantly lower in patients with AN than in either the control subjects or the patients without AN (P < 0.01). The dominant frequency instability coefficient (DFIC) was significantly higher in patients with and without AN than in the control subjects (P < 0.01). The postprandial-to-fasting power ratio (PR) was the lowest in patients with AN (P < 0.01). Multiple regression analysis revealed that HbA1c levels were independently associated with the DFIC (R2 = 0.099, P = 0.0170) and that AN and HbA1c levels were independently associated with the PR (R2 = 0.378, P < 0.0001) in diabetic patients. The percentage of normal DF increased and the DFIC decreased significantly after glycemic control in 12 diabetic patients (P = 0.0409; P = 0.0096, respectively). CONCLUSIONS: There appears to be an association between improvement in gastric myoelectrical activity and autonomic nerve function. Abnormalities of gastric myoelectrical activity may be partly ameliorated via the improvement of autonomic nerve function, which accompanies glycemic control.

Adult↗