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M Nose

Publications and source records attributed to M Nose.

At least 145 records · Page 8Linked to original sources
PubMed1992

Long term beta-adrenoceptor-mediated up-regulation of Gi alpha and G(o) alpha mRNA levels and pertussis toxin-sensitive guanine nucleotide-binding proteins in rat heart.

Chronic stimulation of beta-adrenoceptors leads to increased mRNA and protein levels of pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in the heart. In the present study the time course is reported of the effect of isoprenaline infusions on myocardial mRNA levels of Gi alpha-2, Gi alpha-3, G(o) alpha, Gs alpha, and G beta and myocardial levels of PTX-sensitive G proteins. Rats were treated by subcutaneous infusions, with osmotic minipumps, of 0.9% NaCl, isoprenaline (2.4 mg/kg/day), propranolol (9.9 mg/kg/day), or a combination thereof for 1, 2, 3, 4, or 8 days, and two groups were treated with NaCl or isoprenaline for 13 or 26 days. Additional groups of rats were treated with 0.24 or 0.07 mg/kg/day for 4 days to determine the dose dependency of the effects of isoprenaline. mRNA concentrations were determined by standardized slot blotting with 32P-labeled cDNA or cRNA probes. In isoprenaline-treated rats, mRNA levels of all members of the Gi alpha/G(o) alpha family increased gradually in parallel. The increase in Gi alpha-2, Gi alpha-3, and G(o) alpha mRNA levels reached significance on days 2-3, reached maximal values on days 3-4, and remained stable over the total time of treatment of up to 26 days. Compared with NaCl, maximal increases were 77% (Gi alpha-2; 16.4 versus 9.3 pg/micrograms), 58% (Gi alpha-3; 4.65 versus 2.95 pg/micrograms), and 78% (G(o) alpha; 0.40 versus 0.22 pg/microgram). Gs alpha mRNA levels (about 30 pg/micrograms) and G beta mRNA levels remained unchanged. In isoprenaline-treated rats myocardial levels of PTX-sensitive G proteins increased by maximally 54%, compared with control. The time course differed slightly from the time course of mRNA up-regulation in the first 3 days of treatment and paralleled the increase in mRNA levels from day 4 on. Propranolol had no effect on G alpha mRNA or protein levels when given alone but abolished all effects of isoprenaline when given in combination. Isoprenaline at a dose of 0.24 mg/kg/day still induced an increase in Gi alpha-2 mRNA levels of 24%, without any effects on histopathology of the myocardium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

IgG3 production in MRL/lpr mice is responsible for development of lupus nephritis.

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop lethal glomerulonephritis (GN) similar to human lupus nephritis, associated with the expression of lymphoproliferation gene lpr. To examine whether a particular IgG subclass is responsible for development of GN in these mice, first quantitative analysis of IgG subclasses in serum and in kidney eluates was performed. Although IgG2a was the dominant subclass in serum throughout the lifespan of mice, the IgG3 level in kidney eluates was three times higher than that of IgG2a at the 16 wk of age, which is the time of onset of development of severe GN. In sera of the 12-wk-old mice, half of the IgG3 was in immune complex form, whereas IgG2a in this form was only 17% of the total amount. Second, cyclosporin A, which ameliorates GN in MRL/lpr mice despite autoantibody production, was found to reduce serum IgG3 and mRNA levels, associated with the revision of cationic shift of the serum IgG3 spectrotype seen in isoelectric focusing. Third, among the hybrid mice with non-autoimmune-prone C3H/HeJ-lpr/lpr (C3H/lpr) mice, MRL/lpr x (MRL/lpr x C3H/lpr) F1, in which the genetic background for GN is likely segregated, the mRNA level for IgG3 correlated well with the degree of glomerular lesion. These findings indicate that production of IgG3 in MRL/lpr mice is one of the major factors responsible for development of GN in these mice, and that this is due to the genetic background of the MRL strain.

Animals↗
PubMed1991

Essential role of macrophage colony-stimulating factor in the osteoclast differentiation supported by stromal cells.

Severe deficiency of osteoclasts, monocytes, and peritoneal macrophages in osteopetrotic (op/op) mutant mice is caused by the absence of functional macrophage colony-stimulating factor (M-CSF). To clarify the role of M-CSF in the osteoclast differentiation, we established a clonal stromal cell line OP6L7 capable of supporting hemopoiesis from newborn op/op mouse calvaria. Although very few macrophages appeared in the cocultures of bone marrow cells and OP6L7 cells, a 50-fold larger number of macrophages was detected in the day 7 cocultures when purified recombinant human M-CSF (rhM-CSF) was exogenously supplied. Tartrate-resistant acid phosphatase (TRACP; a marker enzyme of osteoclasts)-positive cells appeared only when bone marrow cells were cultured in contact with OP6L7 cells and both rhM-CSF and 1 alpha, 25 (OH)2D3 were added. The TRACP-positive cells became multinucleated with increasing time in culture and expressed the c-fms/M-CSF receptor. These results indicate that both contact with stromal cells and M-CSF are requisite for osteoclast differentiation under physiological conditions.

Acid Phosphatase↗
PubMed1991

Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by injections of macrophage colony-stimulating factor.

Osteopetrotic (op/op) mice have a severe deficiency of osteoclasts, monocytes, and peritoneal macrophages because of a defect in the production of functional macrophage colony-stimulating factor (M-CSF) resulting from a mutation within the M-CSF gene. In this study, we examined whether daily 5-microgram injections of purified recombinant human M-CSF (rhM-CSF) for 14 d would cure these deficiencies in the mutant mice. Monocytes in the peripheral blood of the op/op mice were significantly increased in number after subcutaneous injections of the factor two or three times a day. In contrast, osteopetrosis in the long bones of op/op mice was completely cured by only one injection of rhM-CSF per day. Bone trabeculae in the diaphyses were removed. Many osteoclasts were detected on the surface of bone trabeculae in the metaphyses. Although development of tooth germs of uninjected op/op mice was impaired, rhM-CSF injection restored the development of molar tooth germs and led to tooth eruption as a consequence of the recovery of bone-resorbing activity. These results demonstrate that M-CSF is one of the factors responsible for the differentiation of osteoclasts and monocyte/macrophages under physiological conditions.

Animals↗
PubMed1991

Mechanism underlying the reduced positive inotropic effects of the phosphodiesterase III inhibitors pimobendan, adibendan and saterinone in failing as compared to nonfailing human cardiac muscle preparations.

The present study was performed to compare the effects of the new positive inotropic phosphodiesterase III inhibitors pimobendan, adibendan, and saterinone on the isometric force of contraction in electrically driven ventricular trabeculae carneae isolated from explanted failing (end-stage myocardial failure) with those from nonfailing (prospective organ donors) human hearts. In preparations from nonfailing hearts the phosphodiesterase inhibitors, as well as the beta-adrenoceptor agonist isoprenaline, the cardiac glycoside dihydro-ouabain, and calcium, which were studied for comparison, revealed pronounced positive inotropic effects. The maximal effects of pimobendan, adibendan, and saterinone amounted to 56%, 36% and 45%, respectively, of the maximal effect of calcium. In contrast, in preparations from failing hearts the phosphodiesterase III inhibitors failed to significantly increase the force of contraction and the effect of isoprenaline was markedly reduced. The effects of dihydroouabain and calcium were almost unaltered. The diminished effects of isoprenaline were restored by the concomitant application of phosphodiesterase inhibitors. To elucidate the underlying mechanism of the lack of effect of the phosphodiesterase III inhibitors in the failing heart we also investigated the inhibitory effects of these compounds on the activities of the phosphodiesterase isoenzymes I-III separated by DEAE-cellulose chromatography from both kinds of myocardial tissue. Furthermore, the effects of pimobendan and isoprenaline on the content of cyclic adenosine monophosphate (determined by radioimmunoassays) of intact contracting trabeculae were studied. The lack of effect of the phosphodiesterase inhibitors in failing human hearts could not be explained by an altered phosphodiesterase inhibition, since the properties of the phosphodiesterase isoenzymes I-III and also the inhibitory effects of the phosphodiesterase inhibitors on these isoenzymes did not differ between failing and nonfailing human myocardial tissue. Instead, it may be due to a diminished formation of cyclic adenosine monophosphate in failing hearts, presumably caused mainly by a defect in receptor-adenylate cyclase coupling at least in idiopathic dilated cardiomyopathy. Both the basal and the pimobendan-stimulated or isoprenaline-stimulated contents of cyclic adenosine monophosphate of intact contracting trabeculae from failing hearts were decreased compared with the levels in nonfailing hearts. However, under the combined action of isoprenaline and pimobendan the cyclic adenosine monophosphate level reached values as high as with each compound alone in nonfailing preparations, and in addition the positive inotropic effect of isoprenaline was restored. These findings may have important clinical implications. Along with the elevated levels of circulating catecholamines the positive inotropic effects of the phosphodiesterase inhibitors may be maintained in patients with heart failure.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1991

Isoprenaline-induced increase in mRNA levels of inhibitory G-protein alpha-subunits in rat heart.

Long-term beta-adrenergic stimulation has been shown to desensitize the beta-adrenoceptor/adenylyl cyclase signalling pathway at both the receptor and the G-protein level. To further elucidate the cellular mechanism of G-protein regulation we investigated the influence of prolonged infusion of isoprenaline (2.4 mg/kg.d) on myocardial mRNA levels of different G-protein alpha-subunits in rats. For comparison rats were treated with triiodothyronine (T3; 0.5 mg/kg.d) which induces cardiac hypertrophy like isoprenaline but has different effects on the adenylyl cyclase system. Isoprenaline- and T3-treated animals developed an increase in heart/body weight ratio of 41 +/- 3% and 27 +/- 4%, respectively (P less than 0.05). Isoprenaline increased myocardial total RNA concentration by 39 +/- 6% (P less than 0.05). Hybridization with 32P-labeled rat cDNAs demonstrated an expression rank order of Gs alpha-mRNA greater than Gi alpha-2-mRNA greater than Gi alpha-3-mRNA and no detectable expression of Gi alpha-1-mRNA in rat myocardium. mRNA levels of Gs alpha, Gi alpha-2 and Gi alpha-3 were 36.9 +/- 1.28, 10.7 +/- 1.07 and 3.7 +/- 0.19 pg/micrograms total RNA, respectively. Isoprenaline increased Gi alpha-2- and Gi alpha-3-mRNA concentrations per microgram total RNA by 49 +/- 18% and 27 +/- 7%, respectively (P less than 0.05). This effect was abolished by simultaneously administered propranolol (9.9 mg/kg.d), indicating a beta-adrenoceptor-mediated mechanism. In contrast, T3-induced cardiac hypertrophy was not accompanied by changes in Gi alpha-mRNA expression. Gs alpha-mRNA levels were unaffected by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

High energy underwater shock wave treatment on implanted urinary bladder cancer in rabbits.

The effects of focused high energy shock waves (SW) on the implanted urinary bladder cancer in rabbits were examined. The bladder cancer was exposed to 2000 to 8000 shots of focused SW under ultrasound guidance. Although only focal necrosis of the tumor was seen in the one day SW exposure, wider and deeper tumor necrosis was observed in the tumors following serial SW (2000 to 6000 shots, for two to three days). Eight to 10 day serial SW exposure (6000 to 8000 shots) decreased the tumor growth in comparison with that of the control. Lung metastases examined by periodic chest X-ray after SW treatment revealed that SW did not promote lung metastases. Pathological findings were also in accord with the X-ray examinations. Polyclonal antibody type 4 collagen was used for immunohistochemical staining of vascular wall in bladder cancer. Vascular wall destruction, not found in spontaneous necrotic tumor, were clearly visible in SW induced necrotic area. SW induces vascular damage in the tumor, which may be the primary cause promoting the tumor necrosis.

Animals↗
PubMed1991

Expression of decay-accelerating factor is reduced on hyperplastic synovial lining cells in rheumatoid synovitis.

Decay-accelerating factor (DAF), a membrane inhibitor of homologous complement activation, is present in synovial cells lining joint space and detected in synovial fluid. DAF is considered to protect synovial membrane from complement-mediated injury associated with articular inflammation. We studied the immunohistopathological features of DAF molecules in synovial membrane of rheumatoid synovitis using a DAF-specific monoclonal antibody, 1C6. Reacting molecules with the 1C6 antibodies in synovial tissue extracts formed a 70-kD band in Western blot analysis. DAF was strongly detected on the flat synovial lining cells, but weakly on the hyperplastic and multi-layered lining cells in rheumatoid synovitis. The latter cells reacted with anti-Leu-M3 antibodies specific for a cell surface marker of activated macrophages, sometimes accompanied by C3 and IgM deposition on the superficial synovial membrane. These results suggest that active rheumatoid synovitis characteristically with hyperplastic synovial lining cells is out of control by DAF, thereby permitting further complement-mediated injury.

Antibodies, Monoclonal↗
PubMed1991

A new mouse strain manifesting high proteinuria and kidney glomerular defect.

A mutant strain of mice manifesting high proteinuria, wasting syndrome, and kidney glomerular defect was established from the F5 offspring of an interstrain cross of CBA/Nga and RFM/Nga mice. Affected mice had high levels of proteinuria after 40 days of age. The body weight of about 22.6% of affected mice decreased rapidly and they died between 3 and 5 months of age. We learned that this abnormality is controlled by two pairs of autosomal recessive genes; the mutant strain of mice is designated FGS/Nga. The mutant strain has been characterized by high proteinuria and renal lesions with focal sclerosis of glomeruli and tubular atrophy with interstitial nephritis in the kidney resembling the human disease. The FGS/Nga mouse strain is a potential animal model for studying kidney glomerular defect in humans.

Animals↗
PubMed1991

Pathogenic significance of serum components in the development of autoimmune polyarthritis in MRL/Mp mice bearing the lymphoproliferation gene.

MRL/Mp mice bearing the lymphoproliferation gene (lpr) (MRL/Mp-lpr/lpr) spontaneously develop polyarthritis, associated with autoimmune traits, including rheumatoid factor production, which resembles rheumatoid arthritis. To investigate possible arthritogenic activity of serum of these mice, intraarticular injections of the serum components to knee joints of nonarthritic MRL/Mp mice not bearing the lpr gene (MRL/Mp(-)+/+) were performed. Two fractions from the serum were obtained by a gel chromatography. The void fraction (VF), but not the nonvoid fraction (NVF), induced acute inflammatory lesions in the joints by single injection, and destructive arthritis by repeated injections. VF had immune complex activity, and contained a large amount of cryoglobulin, which in itself was found arthritogenic. These findings indicate that the serum components of MRL/Mp-lpr/lpr mice have a potency to cause destructive arthritis. These results are direct evidence in a syngeneic animal model system, which suggests the pathogenic significance of serum components in rheumatoid arthritis.

Animals↗
PubMed1990

Structural changes in the oligosaccharide chains of IgG in autoimmune MRL/Mp-lpr/lpr mice.

The structures of the asparagine-linked oligosaccharide chains of IgG from autoimmune arthritic MRL/Mp-lpr/lpr (MRL-lpr/lpr) mice and control MRL/Mp(-)+/+ (MRL(-)+/+) mice were investigated. Two subpopulations of IgG, M1-I and M1-II, were obtained from serum of MRL-lpr/lpr mice by column chromatography on protein A-Sepharose CL-4B. Although M1-I did not bind to the column, its elution was retarded, whereas M1-II was bound and was eluted in acidic buffer. IgG (Mn) from MRL(-)+/+ mice showed the same chromatographic behavior as M1-II. The structures of oligosaccharide chains liberated quantitatively by hydrazinolysis from IgG samples Mn, M1-I, M1-II, and a pooled mixture (M1) of M1-I and M1-II were determined by sequential exoglycosidase digestion, lectin (RCA120) affinity HPLC, and by methylation analysis. Their oligosaccharide structures were the same and shown to be biantennary complex-type chains +/- Gal beta 1----4GlcNAc beta 1----2Man alpha 1----6(+/- Gal beta 1----4GlcNAc beta 1----2Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(+/- Fuc alpha 1----6)GlcNAc. The proportion of each oligosaccharide in Mn and M1-II was the same but differed from that in M1-I where the degree of the galactosylation was significantly decreased which caused the change in the oligosaccharide pattern of total serum IgG (M1) of autoimmune MRL-lpr/lpr mice. This phenomenon, which is also found in total serum IgG of patients with rheumatoid arthritis, suggests that alteration of oligosaccharides in IgG may be a common feature in animals which develop arthritis with the production of rheumatoid factor regardless of species.

Animals↗
PubMed1990

Effects of recombinant human granulocyte colony-stimulating factor on the hematologic recovery and survival of irradiated mice.

We studied the effects of intraperitoneal injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) according to various administration schedules on the recovery of spleen colony-forming units (CFU-S) and peripheral blood counts, and on the survival of irradiated mice. The sooner and more frequently the mice were injected with rhG-CSF after irradiation, the more enhanced the recovery of CFU-S in bone marrow was obtained on day 7. Twice-daily injections of rhG-CSF from day 0 to day 2 significantly enhanced the recovery of platelets and hematocrit, but two injections of rhG-CSF on only day 0 did not. Twice-daily injections of rhG-CSF from day 0 to day 6 enhanced the recovery of platelets more effectively than twice-daily injections of rhG-CSF from day 1 to day 7, and increased the survival of irradiated mice more effectively than any other examined administration schedules. Twice-daily injections of rhG-CSF from day 0 to day 6 were significantly effective in enhancing the survival of mice irradiated with 8.5-, 9.0-, and 9.5-Gy x-rays, although not effective after irradiation of 10.5-Gy x-rays.

Animals↗
PubMed1990

Inhibition of processing of asparagine-linked carbohydrate chains on IgG2a by using swainsonine has no influence upon antibody effector functions in vitro.

Removal of asparagine (Asn)-linked carbohydrate chains from IgG antibody molecules reduces their antibody effector functions such as C activation and FcR binding. We have prepared IgG2a mAb with modified structure of carbohydrate chains by treating the hybridoma cells with swainsonine, which inhibits the processing of Asn-linked carbohydrate chains at the site of action of mannosidase II. These antibodies have obtained the capacity to bind lentil lectin and have become sensitive to endoglycosidase H digestion, indicating the structural changes of oligosaccharides from complex type to hybrid type. They behaved in an identical manner to the normal IgG2a antibodies with regards to extracellular secretion, Ag-binding capacity, C-mediated hemolysis and FcR-mediated functions. Critical moieties of Asn-linked carbohydrate chains on IgG molecules to retain their antibody effector functions were discussed.

Acetylglucosaminidase↗
PubMed1990

Evidence of IgG-mediated enhancement of the antibody response in vivo without complement activation via the classical pathway.

The complement (C) dependency of IgG-mediated enhancement of the antibody response was investigated by immunizing mice with trinitrophenyl-coupled keyhole limpet hemocyanin (TNP-KLH) and either a C-activating TNP-specific monoclonal IgG2a antibody (Hy-1.2) or a mutant, non-C-activating variant of Hy-1.2 (M12). Hy-1.2 as well as M12 efficiently enhanced the anti-KLH response, although Hy-1.2 was more active. In addition, also a naturally non-C-activating TNP-specific IgG1 antibody enhanced the response to TNP-coupled bovine serum albumin. Moreover, C-activating IgG could enhance the antibody response in mice depleted of C3 by treatment with cobra venom factor. These findings suggest that the classical pathway of C activation is not required for IgG-mediated enhancement.

Animals↗
PubMed1990

Proton nuclear magnetic resonance studies of the structure of the Fc fragment of human immunoglobulin G1: comparisons of native and recombinant proteins.

The structure of the Fc fragment of human IgG1 immunoglobulin is compared for the native and recombinant proteins. A recombinant human Fc fragment was expressed by an E. coli system [Kitai K., Kudo T., Nakamura S., Masegi T., Ichikawa Y. and Horikoshi K. (1988) Appl. Microbiol. Biotechnol. 28, 52-56]. The recombinant protein, which presumably lacks oligosaccharides, was used along with the native human Fc fragment obtained by proteolytic digestion of a myeloma IgG1 protein. 1H NMR has been employed along with circular dichroism and fluorescence spectroscopy to discuss the structure of these two types of proteins. It has been concluded that (1) the overall structure of the recombinant protein is quite similar to that of the native protein, which possesses asparagine-linked oligosaccharides, but (2) a significant difference in structure exists in the neighborhood of the glycosylation site. The difference in the effector functions for the two kinds of the Fc proteins has been briefly discussed in terms of the structural change detected by 1H NMR.

Amino Acid Sequence↗
PubMed1990

Recombinant Fc of human IgG1 prepared in an Escherichia coli system escapes recognition by macrophages.

The Fc portion of IgG is recognized by macrophages via Fc receptors on their cell surface. The recognition of human IgG1-Fc by macrophages was compared for the native and recombinant proteins by a novel assay method using competitive inhibition of the aggregated IgG-mediated chemiluminescence reaction of human macrophage cell line THP-1. Recombinant Fc proteins, prepared in an Escherichia coli system, which lack oligosaccharides and retain normal staphylococcal protein A reactivity and, to a lesser extent, C1q binding capacity, showed inhibitory ability greater than 500 times lower than that of native Fc fragments obtained by proteolytic digestion of myeloma proteins. This suggests that the oligosaccharide chains on IgG1-Fc molecules may be critical for recognition by Fc receptors on macrophages.

Amino Acid Sequence↗
PubMed1990

Gastroenteritis in suckling mice caused by human rotavirus can be prevented with egg yolk immunoglobulin (IgY) and treated with a protein-bound polysaccharide preparation (PSK).

Oral inoculation of human rotavirus MO strain (serotype 3) into 5-day-old BALB/c mice cause gastroenteritis characterized by diarrhea. Clinical symptoms, histopathological changes in the small intestine, and the detection of rotavirus antigen in enterocytes were all characteristic of rotavirus-induced gastroenteritis. Using this small animal model, passive protection of suckling mice against human rotavirus infection was achieved with the use of immunoglobulin (IgY) from the yolks of eggs of rotavirus-immunized hens. When IgY against a rotavirus strain homotypic to the challenge virus (MO strain) was administered in the mice, complete protection against rotavirus infection was achieved. On the other hand, with oral administration of IgY against a heterotypic strain (serotype 1, Wa strain), a lower protective effect was nevertheless obtained. The four different strains of human rotavirus (Wa, KUN, MO, and ST3) were inactivated in vitro by treatment with PSK, a protein-bound polysaccharide preparation, in a dose-dependent manner. Oral administration of 2.5 mg of PSK caused a therapeutic effect on experimentally MO-infected suckling mice. The antiviral effect of PSK was indicated by the reduction of the duration of diarrhea.

Animals↗