Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

At least 271 records · Page 15Linked to original sources

PubMed1993

Concomitant enhancement of the response to Mls-1a antigens and the induction of post-thymectomy autoimmune gastritis in BALB/c mice.

We examined the role of Mls antigens in the induction of autoimmune gastritis (AIG) in BALB/c and DBA/2 mice subjected to thymectomy. The prevalence of AIG in Mls-1b mice which underwent thymectomy on day 3 after birth (3d-Tx) was 78% (mean), while in Mls-1a DBA/2 mice it was < 6%. Whereas AIG-negative 3d-Tx DBA/2 mice produced 2-mercaptoethanol (2-ME)-sensitive antiparietal cell autoantibody, AIG-positive BALB/c mice made 2-ME-resistant anti-parietal cell autoantibody. In addition, the prevalence of AIG in 3d-Tx BALB/c mice which were rendered tolerant to MIs-1a antigens by injection of bone marrow cells from (BALB/c x DBA/2)F1 mice within 24 h after birth was decreased compared with the non-tolerant control mice; the prevalence being 80% in the controls and 30% in the tolerant animals. Thus, the activation of helper T cells, including T cells responding to Mls-1a antigens and including immunoglobulin class switch, appeared to be closely associated with the induction of AIG. Flowcytometric analysis confirmed that CD4- V beta 6 T cells had increased in the regional lymph nodes of the stomach in AIG mice. However, an increase in the number of V beta 11 T cells, which are known to increase in 3d-Tx mice, occurred in the CD8, but not in the CD4 T cell population. Injection of MoAb to L3T4, but not Lyt2, V beta 6- or V beta 8-TCR, into 3d-Tx BALB/c and syngeneic nude mice which had received spleen cells of 3d-Tx BALB/c mice bearing AIG completely abrogated the development of AIG, despite there being remarkable decreases in T cells expressing relevant markers to the injected antibodies in all the mice. These findings suggest that the increase of V beta 6+ L3T4+ T cells in AIG mice was concomitant with the activation of AIG-inducing V beta 6- L3T4+ T cells.

Animals↗

PubMed1993

Effect of uremic serum on 1,25-dihydroxyvitamin D3-induced differentiation of human promyelocytic leukemia cell, HL-60.

The mechanism by which resistance to 1,25-(OH)2D3 occurs in patients with chronic renal failure was studied. 1,25-(OH)2D3 causes the induction of differentiation and of 1,25-(OH)2D3-24-hydroxylase activity in the mitochondria of the human promyelocytic leukemia cell line, HL-60, via a steroid hormone-receptor mechanism. Treatment of these cells with 10(-8) M 1,25-(OH)2D3 for 5 days in a medium containing 10% uremic serum from 4 patients with chronic renal failure resulted in maturation of the cells amounting to 30.3 +/- 18.7 (mean +/- SD) and 32.5 +/- 11.2% maturation by the nitroblue tetrazolium reduction assay and the nonspecific esterase assay, respectively. These values were significantly lower than those obtained with 10% normal serum from 3 normal controls (66.6 +/- 12.8 and 58.3 +/- 10.9%, p < 0.02). The occurrence of resistance to 1,25-(OH)2D3 in uremic serum-treated cells was also confirmed when the effect of 1,25-(OH)2D3 was assessed by the induction of the cell's ability to hydroxylate the C-24 position of 1,25-(OH)2[3H]D3. Treatment of HL-60 cells with a mixture of 5% uremic plus 5% normal serum impaired 1,25-(OH)2D3-induced cell differentiation to the levels as those in 10% uremic serum, strongly suggesting the occurrence of a substance(s) having 1,25-(OH)2D3-inhibitory activity in the uremic serum. A significant reduction in 1,25-(OH)2D3 receptor levels was observed in uremic serum-treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

PubMed1993

A novel response of anion transporter in equine erythrocytes to a fluorescent substrate, N-(2-aminoethyl sulfonate)-7-nitrobenz-2-oxa-3-diazole (NBD-taurine).

This report describes a unique response of the anion transporter in equine erythrocytes to the fluorescent substrate N-(2-aminoethyl sulfonate)-7-nitrobenz-2-oxa-3-diazole (NBD-taurine). Equine erythrocytes showed fluxes of NBD-taurine both inward and outward at rates considerably slower than those in human cells. These fluxes were completely abolished by a typical anion transport inhibitor, 4,4'-diisothiocyanostilbene-2,2'-disulfonate. Furthermore, NBD-taurine competitively inhibited the uptake of phosphate in equine red cells with an inhibition constant of phosphate that was slightly higher than the Michaelis constant of phosphate uptake. These results demonstrate that the anion transporter (band 3) in equine red cells binds NBD-taurine but does not prefer it as the substrate for transport, suggesting a structural difference between equine and human anion transporters at the polypeptide portion which is implicated in anion transport.

Animals↗

PubMed1993

Effects of captopril or nitrendipine on left ventricular collagen or laminin B2 gene expression.

A study was designed to clarify the effects of captopril (CAP) or nitrendipine (NITR) on cardiac hypertrophy and left ventricular expression of the laminin B2 or collagen (COL) gene in spontaneously hypertensive rats (SHRs). Cardiac weight was significantly increased in 20-week-old SHRs. Gene expression of the alpha 1 chain of type IV COL determined by northern blot analysis decreased with age in Wistar-Kyoto rats and SHRs. Left ventricular laminin B2 mRNA was decreased at 12 weeks and increased again at 20 weeks in both strains. Daily oral administration of CAP (40 mg/kg, n = 5) or NITR (30 mg/kg, n = 4) to SHRs from 8 to 20 weeks decreased blood pressure to 142 mmHg (p < 0.01 vs 197 mmHg in controls, n = 5). Cardiac weight was 1.26 +/- 0.04 (SE) g in controls and was reduced to 1.03 +/- 0.05 g (p < 0.01) by CAP, but not by NITR (1.24 +/- 0.04). Left ventricular laminin B2 gene expression was attenuated by CAP and NITR to 41% and 32% of the control value, respectively. CAP significantly decreased left ventricular alpha 1 type IV COL mRNA to 11% of the control level, whereas NITR caused a reduction only to 75%. CAP also decreased alpha 1 or alpha 2 type I COL mRNA. These results suggest that angiotensin converting enzyme inhibitors prevent and/or cause regression of cardiac hypertrophy by inhibiting the gene expression of extracellular matrix, and that angiotensin II may have a pivotal role in cardiac hypertrophy.

Animals↗

PubMed1993

Thyroid follicle transplantation by percutaneous injection.

We previously reported on the isolation of thyroid follicles from thyroid tissue and their acceptance after allogeneic transplantation under the renal capsule with laparotomy in mice. In the present study, we introduced a new method of autologous transplantation of thyroid follicles accepted in the hosts after percutaneous injection into the spleen or into fat tissue in the peritoneal cavity without laparotomy in rats. This method of thyroid transplantation by a single injection, which induces little stress in the host, is applicable to autologous and allogeneic transplantations and may release patients from the burden of daily life-long administration of thyroxine.

Animals↗

PubMed1993

Functional analyses of B cells in (NZW x BXSB) F1 mice.

Functions of B cells from (NZW x BXSB)F1 (W/BF1) mice are investigated. The W/BF1 mouse, which is an animal model for systemic lupus erythematosus (SLE) and immune thrombocytopenic purpura (ITP), produces anti-DNA and anti-platelet antibodies; W/BF1 mice show hypergammaglobulinemia (particularly increases in IgG2a and IgG2b). The ratio of small resting B cells to large activated B cells in W/BF1 mice is low compared to normal mice, suggesting that B cells in W/BF1 mice are already activated in vivo. Furthermore, small resting B cells separated by a Percoll density gradient technique show hyper-responsiveness to lipopolysaccharide (LPS) or anti-mu plus IL-4. This suggests that B cells in W/BF1 mice are genetically programmed to be easily activated, resulting in the overproduction of autoantibodies. A significant number of CD5+ B cells are found in the lymph nodes of old W/BF1 mice. These findings indicate that all cells in the B cell lineage of W/BF1 mice are already activated in vivo.

Animals↗

PubMed1993

Comparison of reversed and in situ saphenous vein grafts for infragenicular bypass: experience of two surgeons.

A series of 241 consecutive autogenous vein bypasses for chronic lower-limb ischaemia performed by two surgeons since 1980 was reviewed. After 1985, in situ vein bypass was employed preferentially and was compared with reversed vein bypass. The two groups of patients had similar risk factors, indications and outflow. Of the 241 bypasses, 157 were to the below-knee popliteal artery and 84 to infrapopliteal arteries. The utilization rates of a single ipsilateral saphenous vein were 57.5% for reversed and 71.9% for in situ vein bypass. However, in situ vein bypass was impossible in 43 procedures and these were changed to the reversed operation with contralateral vein. The primary 5-year patency rates of reversed and in situ vein bypass grafts to the popliteal artery were 82.5 versus 74.5%, and the primary 4-year patency rates for infrapopliteal bypass 68.5 versus 80.0%. The respective secondary patency rates were 94.2 versus 92.1% and 85.7 versus 91.1%. The main cause of graft failure was vein graft stenosis (reversed vein bypass, 13.0%; in situ, 11.1%), which usually occurred in the first 2 years after surgery. Of 23 grafts revised for stenosis, 21 were salvaged and restenosis rarely occurred. Both reversed and in situ vein bypass grafts were equally effective, but careful surveillance for 2 years and aggressive revision were extremely important after either type of reconstruction.

Adult↗

PubMed1993

[Isolated ACTH deficiency associated with Hashimoto disease].

Isolated ACTH deficiency is a rare cause of secondary adrenocortical insufficiency. The diagnosis is made by the demonstration of low cortisol production with low plasma ACTH, absent adrenal responses to stimulation for pituitary or hypothalamus with intact adrenal response to exogenous ACTH, and normal secretory indices of other pituitary hormones. Although the pathogenesis of isolated ACTH deficiency is uncertain in most cases, autoimmune process is intimately involved as suggested by the histological evidence of lymphocytic hypophysitis and frequent observation of circulating antipituitary antibodies. In isolated ACTH deficiency, there have been occasional associations with Hashimoto disease which is characterized by the presence of a autoimmune mechanism. This suggests the possibility of common autoimmune process affecting both the pituitary and the thyroid gland.

Adrenocorticotropic Hormone↗

PubMed1993

[Results of arterial reconstruction in Buerger's disease].

One hundred and eight bypass operations for Buerger's disease were performed between November 1976 and August 1990. The bypass procedures, prostheses, cumulative patency rate and the influence of smoking on the results were discussed. Five-year cumulative patency rate of Aorto-femoral bypass was 88.2%. Aorto-femoral bypass should be always indicated as a standard procedure for the iliac lesion in Buerger's disease, because the patency rate was very low in aorto-iliac bypass group or ilio-femoral bypass group. Five-year cumulative patency rate of infrainguinal bypass using autogenous vein was 64.8%, and that in the patients who quit cigarette smoking was as high as to 73.3%. We should use autogenous vein as much as possible for infraiguinal bypass and discontinuance of cigarette smoking is considered to be one of the important factors to improve the patency rate in Buerger's disease.

Adult↗

PubMed1993

[Antitumor activity of a new antiestrogenic drug, toremifene (NK622) against human breast cancer xenografts in nude mice].

NK622, a novel tamoxifen(TAM) analog with nonsteroidal structure is an antiestrogenic drug with less toxicity compared with that of TAM. We studied the in vivo antitumor activity against human breast cancer xenografts in nude mice. NK 622 significantly inhibited the growth of estrogen-dependent Br-10 breast cancer but not inhibited the growth of estrogen-independent MC-2-JCK and MC-5-JCK when orally administered once daily for 14 days at the maximum tolerated dose (200mg/kg/day). The dose of NK622 in animal studies was calculated by measuring plasma level in patients receiving 40 mg/body/day oral treatment and clinically equivalent dose (CED) was determined. At the calculated CED, NK622 significantly inhibited the growth of Br-10. These results indicate that NK622 is a promising drug comparable to TAM because of the growth inhibition of estrogen-dependent breast cancers.

Animals↗

PubMed1992

Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.

Antigen-presenting, major histocompatibility complex (MHC) class II-rich dendritic cells are known to arise from bone marrow. However, marrow lacks mature dendritic cells, and substantial numbers of proliferating less-mature cells have yet to be identified. The methodology for inducing dendritic cell growth that was recently described for mouse blood now has been modified to MHC class II-negative precursors in marrow. A key step is to remove the majority of nonadherent, newly formed granulocytes by gentle washes during the first 2-4 d of culture. This leaves behind proliferating clusters that are loosely attached to a more firmly adherent "stroma." At days 4-6 the clusters can be dislodged, isolated by 1-g sedimentation, and upon reculture, large numbers of dendritic cells are released. The latter are readily identified on the basis of their distinct cell shape, ultrastructure, and repertoire of antigens, as detected with a panel of monoclonal antibodies. The dendritic cells express high levels of MHC class II products and act as powerful accessory cells for initiating the mixed leukocyte reaction. Neither the clusters nor mature dendritic cells are generated if macrophage colony-stimulating factor rather than granulocyte/macrophage colony-stimulating factor (GM-CSF) is applied. Therefore, GM-CSF generates all three lineages of myeloid cells (granulocytes, macrophages, and dendritic cells). Since > 5 x 10(6) dendritic cells develop in 1 wk from precursors within the large hind limb bones of a single animal, marrow progenitors can act as a major source of dendritic cells. This feature should prove useful for future molecular and clinical studies of this otherwise trace cell type.

Animals↗

PubMed1992

In vitro measurement of chemosensitivity of human small cell lung and gastric cancer cell lines toward cell cycle phase-nonspecific agents under the clinically equivalent area under the curve.

BACKGROUND: Based on the previous finding that cell killing effects of cell cycle phase-nonspecific agents depend on the concentration-time product (C x T) or the area under the curve (AUC), the authors investigated in vitro cytotoxic effects of nimustine hydrochloride (ACNU) and mitomycin C (MMC) under an experimental condition in which the assay AUC was equivalent to their clinically achievable AUC. METHODS: The cytotoxic effects of these agents on human cancer cell lines, consisting of 9 small cell lung carcinomas (SCLC) and 10 gastric cancers, were measured by a tetrazolium-based colorimetric assay (MTT assay). RESULTS: These cell lines individually responded to ACNU and MMC in this assay condition. When the authors considered 60% or greater cell kill to be effective, the in vitro response rates of SCLC to ACNU and MMC were 22% (two of nine carcinomas) and 67% (six of nine carcinomas), respectively. The response rates of gastric cancer to ACNU and MMC were 10% (1 of 10 carcinomas) and 40% (4 of 10 carcinomas), respectively. Except for the response of SCLC to ACNU, these in vitro response rates corresponded well to the clinical rates (SCLC to ACNU and MMC, 47% [14 of 30 carcinomas] and 50% [17 of 34 carcinomas], respectively; gastric cancer to ACNU and MMC, 11% [4 of 37 carcinomas] and 30% [63 of 211 carcinomas], respectively). CONCLUSIONS: These results suggest that the introduction of the clinically equivalent AUC to the in vitro chemosensitivity test for cell cycle phase-nonspecific agents may improve its clinical predictability.

Carcinoma, Small Cell↗

PubMed1992

Bone marrow transplantation as a strategy for treatment of non-insulin-dependent diabetes mellitus in KK-Ay mice.

The effects of allogeneic bone marrow transplantation (BMT) on non-insulin-dependent diabetes mellitus (NIDDM) were examined using KK-Ay mice. KK-Ay mice reconstituted with KK-Ay bone marrow cells showed glycosuria, hyperinsulinemia, and hyperlipidemia. However, KK-Ay mice (H-2b) that had been lethally irradiated (9.0 Gy) and then reconstituted with T cell-depleted bone marrow cells from normal BALB/c mice (H-2d) showed negative urine sugar with decreases in serum insulin and lipid levels 4 mo after BMT. Morphological recovery of islets and glomeruli was also noted after allogeneic BMT. These findings suggest that BMT can be used to treat not only a certain type of NIDDM but also its complications such as hyperlipidemia and diabetic nephropathy.

Animals↗

PubMed1992

Separation of hematopoietic stem cells into two populations and their characterization.

Two populations of hematopoietic stem cells (HSC) in mouse bone marrow (BM) are defined on the basis of the presence or absence of interleukin-3 (IL-3) receptor-associated antigen (IL-3RAA). HSC were purified by depletion of mature lymphoid-lineage cells followed by collection of the low-density fraction and sorting of wheat germ agglutinin-binding (WGA+) cells using a fluorescein-activated cell sorter. WGA+ cells were further separated into two populations (IL-3RAA+/WGA+ and IL-3RAA-/WGA+) by a monoclonal antibody (MoAb) against IL-3RAA. IL-3RAA+/WGA+ cells formed CFU-S on day 8; this population consisted mainly of cells in the cycling phase. IL-3RAA-/WGA+ cells form CFU-S on day 12; this population consisted mainly of dormant cells (cells in the G0 phase). When two populations obtained from C3H/HeN mice were injected into lethally irradiated (C57BL/6 x C3H/HeN)F1 mice, donor-derived cells in the peripheral blood (PB) appeared significantly earlier in mice injected with IL-3RAA+/WGA+ cells than in those injected with IL-3RAA-/WGA+ cells, whereas the reconstruction efficiency of IL-3RAA-/WGA+ cells had overtaken that of IL-3RAA+/WGA+ cells 6 weeks after injection. Long-term observation showed no significant difference between these two populations, however. The radioprotective ability (RPA) (30-day survival) of these two populations was therefore compared. The RPA of IL-3RAA-/WGA+ cells was significantly higher than that of IL-3RAA+/WGA+ cells. These findings therefore suggest that the former population is more primitive.

Animals↗

PubMed1992

Deamidation of human erythrocyte protein 4.1: possible role in aging.

The human erythrocyte membrane protein 4.1 exists in two major electrophoretic forms: 4.1a (80 Kd) and 4.1b (78 Kd). Mass spectrometry and amino acid analysis of the proteolytic peptides derived from carboxyl-terminal regions of these proteins indicate that they differ by deamidation of two aspargine residues at positions 478 and 502. Electrophoretic analysis of carboxyl-terminal peptides has shown that the mobility difference between the two polypeptides is due to the deamidation of Asn502 and not that of Asn478. This observation was confirmed by converting a congener of the protein 4.1b to 4.1a by site-directed mutagenesis of Asn502 to Asp. These results unambiguously demonstrate that deamidation of Asn502 is responsible for conversion of protein 4.1b to 4.1a. Since the conversion of protein 4.1b to 4.1a, under physiological conditions, occurs in a time-dependent manner, our study clearly shows that deamidation is an excellent marker for red blood cell aging.

Amino Acid Sequence↗

PubMed1992

Identification of proliferating dendritic cell precursors in mouse blood.

While it has been known that dendritic cells arise from proliferating precursors in situ, it has been difficult to identify progenitors in culture. We find that aggregates of growing dendritic cells develop in cultures of mouse blood that are supplemented with granulocyte/macrophage colony-stimulating factor (GM-CSF) but not other CSFs. The dendritic cell precursor derives from the Ia-negative and nonadherent fraction. The aggregates of developing dendritic cells appear at about 1 wk of culture, with 100 or more such clusters being formed per 10(6) blood leukocytes. The aggregates can be dislodged and subcultured as expanding clusters that are covered with cells having the motile sheet-like processes ("veils") of dendritic cells. By about 2 wk, large numbers of single, major histocompatibility complex (MHC) class II-rich dendritic cells begin to be released into the medium. Combined immunoperoxidase and [3H]thymidine autoradiography show that the cells that proliferate within the aggregate lack certain antigenic markers that are found on mature dendritic cells. However, in pulse-chase protocols, the [3H]thymidine-labeled progeny exhibit many typical dendritic cell features, including abundant MHC class II and a cytoplasmic granular antigen identified by monoclonal antibody 2A1. The progeny dendritic cells are potent stimulators of the mixed leukocyte reaction and can home to the T-dependent areas of lymph node after injection into the footpads. We conclude that mouse blood contains GM-CSF-dependent, proliferating progenitors that give rise to large numbers of dendritic cells with characteristic morphology, mobility, phenotype, and strong T cell stimulatory function.

Animals↗

PubMed1992

Dibutyryl cAMP enhances the effect of 1,25-dihydroxyvitamin D3 on a human promyelocytic leukemia cell, HL-60, at both the receptor and the postreceptor steps.

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) induces differentiation of a human promyelocytic leukemia cell line, HL-60, into monocytes/macrophages, and 25-hydroxyvitamin D3- and 1,25-(OH)2D3-24-hydroxylase activities in HL-60 mitochondria via a steroid-hormone receptor mechanism. Dibutyryl cyclic adenosine monophosphate (dbcAMP), a granulocyte inducer, significantly augmented the differentiation-inducing effect of 1,25-(OH)2D3 along the monocyte/macrophage pathway. Furthermore, dbcAMP significantly potentiated the effect of 1,25-(OH)2D3 on HL-60 cells to hydroxylate 1,25-(OH)2[26,27-3H]D3 to form 1,24,25-(OH)3[26,27-3H]D3. DbcAMP seemed to augment the effect of 1,25-(OH)2D3 in part through upregulation of the 1,25-(OH)2D3 receptor, because 10(-7) M dbcAMP increased 1,25-(OH)2D3 receptor levels approximately 2.3-fold, which was similar to a 1.9-fold augmentation by the same concentrations of dbcAMP of 1,25-(OH)2D3-induced cell characteristics to hydroxylate C-24 of 1,25-(OH)2[26,27-3H]D3. However, dbcAMP is also known to enhance HL-60 cell differentiation caused by other differentiation inducers. We have established another HL-60 clone which acquires resistance to 1,25-(OH)2D3 in the induction of cell differentiation by a defect at the postreceptor step, as reflected by resistance to other differentiation inducers, such as retinoic acid and dimethyl sulfoxide. Even in this resistant clone, dbcAMP significantly enhanced the differentiation-inducing effect of 1,25-(OH)2D3. Of interest, this clone showed resistance to dbcAMP in the induction of cell differentiation. Furthermore, we have demonstrated that intracellular cAMP levels were significantly lower in uremic serum-treated cells than in cells treated with normal human serum and that a significant positive correlation was found between intracellular cAMP levels and 1,25-(OH)2D3-induced cell differentiation. These data indicated that the intracellular cAMP level is one of the major determinants of 1,25-(OH)2D3-induced HL-60 cell differentiation and that dbcAMP could enhance the effects of 1,25-(OH)2D3 on HL-60 cells not only by increasing 1,25-(OH)2D3 receptor levels but also at the postreceptor step.

Bucladesine↗

PubMed1992

Origin of thymic and peritoneal Ly-1 B cells.

Murine Ly-1 B cells were first found in the peritoneal cavity (Per C). It has been thought that Ly-1 B cells are responsible for the development of autoimmune diseases, since they spontaneously produce autoantibodies. However, we have found that such Ly-1 B cells are present in the thymus of normal mice, and that they play a crucial role in negative selection in the Mls system. In addition, thymic Ly-1 B cells and Per C Ly-1 B cells have been found to differ in function, ontogeny and location. In this communication, we report on the different origins of these cells. C57BL/6 mice are lethally irradiated and reconstituted with fetal (day 14) liver cells or bone marrow cells from 4-, 6- or 12-week-old mice. Fetal liver cells are shown to have the capacity to reconstitute both thymic and Per CLy-1 B cells, whereas bone marrow cells from 6- or 12-week-old mice have the capacity to reconstitute thymic Ly-1 B cells, but not Per C Ly-1 B cells, indicating that fetal hemopoietic stem cells (HSC) differ from HSC in the bone marrow of adult mice, and that thymic and Per C Ly-1B cells have different origins.

Age Factors↗