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Biomedical subjects

M Iwata

Publications and source records attributed to M Iwata.

At least 487 records · Page 27Linked to original sources

Augmentation of the antibody response by antigen-specific glycosylation-enhancing factor.

BDF1 mice were immunized with a protein antigen, such as ovalbumin (OA) or keyhole limpet hemocyanin (KLH), absorbed to aluminum hydroxide gel, and their spleen cells were stimulated by homologous antigen for the formation of glycosylation-enhancing factor (GEF). It was found that GEF obtained from OA-primed spleen cells had affinity for OA, whereas those derived from KLH-primed spleen cells had affinity for KLH. Nonspecific GEF, which was obtained by stimulation of normal spleen cells with pertussis toxin, failed to bind OA or KLH. Both antigen-specific GEF and nonspecific GEF are inactivated by phenylmethylsulfonyl fluoride, but not by N-alpha-p-tosyl-L-lysyl-chloromethyl ketone. Both factors can be partially purified by binding to p-aminobenzamidine agarose and elution with benzamidine. These findings suggest that not only non-specific GEF but also antigen-specific GEF are serine protease(s). The antigen-specific GEF consisted of two m.w. species, of 65 to 85 kilodaltons (Kd) and 40 to 55 Kd, whereas nonspecific GEF consisted of 50 to 70 Kd and 20 to 30 Kd molecules. The OA-specific GEF augmented the in vitro secondary indirect PFC response of DNP-OA-primed cells to the homologous antigen, but failed to affect the PFC response of DNP-KLH-primed cells to DNP-KLH. Similarly, KLH-specific GEF enhanced the response of DNP-KLH-primed cells but not the response of DNP-OA-primed cells. However, OA-specific GEF failed to replace the requirement for antigen-primed helper T cells. Antigen-specific GEF bound to alloantibodies reactive to the products of the I region of the major histocompatibility complex. The results collectively suggest that antigen-specific GEF is identical to antigen-specific augmenting factors described by other investigators.

Animals↗

Myoclonus in Alzheimer's disease.

Myoclonus was studied electrophysiologically in seven patients with clinically diagnosed Alzheimer's disease. There seem to be at least two physiological types of myoclonus in Alzheimer's disease. Cerebral cortical structures might participate in the generation of myoclonus in one type, while the other type is probably generated by subcortical structures.

Aged↗

Formation of IgM-binding factors by murine thymocytes.

Normal mouse thymocytes activated with concanavalin A (Con A) released soluble factors which selectively inhibited rosette formation between human peripheral blood lymphocytes (PBL) and ox erythrocytes (Eo) sensitized with rabbit IgM antibodies. The factors were removed by absorption with mouse IgM-coupled Sepharose, and were recovered from the beads by elution at acid pH. They neither bound to mouse IgG-Sepharose nor inhibited rosette formation of PBL with Eo sensitized with rabbit IgG antibodies. Mouse IgM enhanced the formation of IgM-binding factors by Con A-activated thymocytes. Unstimulated normal mouse thymocytes also released IgM-binding factors upon incubation with mouse IgM. The molecular weights of IgM-binding factors were approximately 90-110 and 35-50 kDa as estimated by gel filtration. Each species of IgM-binding factors markedly suppressed the IgM-plaque-forming cell (PFC) response of sheep red blood cell-primed spleen cells and slightly suppressed the IgG PFC response.

Animals↗

Immunohistochemical studies of major histocompatibility antigens in a case of the bare lymphocyte syndrome without immunodeficiency.

A case of the bare lymphocyte syndrome without apparent immunodeficiency was observed. The patient had, in addition, ichthyosis vulgaris and sinobronchial disease. A pustular lesion developed at first on the anterior aspect of lower part of the left leg. This lesion gradually increased in size and evolved into giant indurated, irregular adjoining plaques. On biopsy, the histologic findings were similar to necrobiosis lipoidica. No human lymphocyte antigen (HLA) class I antigens were detected on peripheral mononuclear cells; however, HLA-DR antigens were present on B lymphocytes. Immunohistochemical studies disclosed defective expression of class I antigens in the non-lesional skin, but positive expression was demonstrated in the lesional area. HLA-DR antigens were expressed on keratinocytes and on most infiltrating inflammatory cells in the affected skin. It is therefore speculated that class I antigen appearance and mononuclear cell infiltrate each induces the other and that together they play an important role in the formation and enlargement of the skin lesion.

Adult↗

In vitro modulation of antigen-primed T cells by a glycosylation-inhibiting factor that regulates the formation of antigen-specific suppressive factors.

BDF1 [(C57BL/6 X DBA/2)F1] mice were primed with alum-absorbed ovalbumin, and their spleen cells were cultured with ovalbumin to activate antigen-primed T cells. The activated T cells were then propagated in interleukin 2-containing medium in the presence or absence of affinity-purified glycosylation-inhibiting factor (GIF). Upon incubation with ovalbumin-pulsed macrophages, T cells propagated in the absence of GIF produced IgE-potentiating factor and glycosylation-enhancing factor. In contrast, T cells propagated in the presence of GIF produced IgE-suppressive factor and GIF. The ovalbumin-primed T cells propagated in the presence of GIF constitutively produced the 13-kDa GIF that lacked affinity for ovalbumin. However, stimulation of the same T cells with ovalbumin-pulsed macrophages resulted in the production of 80- and 35-kDa GIF that had affinity for ovalbumin. Both the antigen-specific GIF and nonspecific GIF from the activated BDF1 T cells had I-Jb determinants. Since the ovalbumin-specific GIF is derived from Lyt-2+, I-J+ ovalbumin-specific suppressor T cells and suppresses the anti-hapten antibody response to dinitrophenyl-coupled ovalbumin, the results strongly suggest that the presence of GIF during the propagation of antigen-primed T cells facilitates the generation of antigen-specific suppressor T cells.

Animals↗

Effect of exogenous gangliosides on amino acid uptake and Na+, K+-ATPase activity in superior cervical and nodose ganglia of rats.

The effects of some gangliosides on active uptake of nonmetabolizable alpha-aminoisobutyric acid (AIB) and Na+, K+-ATPase and Ca2+, Mg2+-ATPase activities in superior cervical ganglia (SCG) and nodose ganglia (NG) excised from adult rats were examined during aerobic incubation at 37 degrees C for 2 h. In NG, amino acid uptake was greatly accelerated with the addition of galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylgluc osyl ceramide (GM1) (85%) and also with N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosyl ceramide (GM2) or [N-acetylneuraminyl]-galactosyl-N-acetylgalactosaminyl-[N-acetyl- neuraminyl]-galactosylglucosyl ceramide (GD1a) (43% each) compared with a nonaddition control at a 5 nM concentration. Under identical conditions, Na+, K+-ATPase activity was strongly stimulated with GM1 (180%) and GD1a (93%), whereas Ca2+, Mg2+-ATPase activity showed no change. In SCG, on the other hand, AIB uptake was apparently inhibited (-27%) by addition of GM1, with a slight decrease in Na+, K+-ATPase but no change in Ca2+, Mg2+-ATPase activity in the tissue. Both asialo-GM1, in which N-acetylneuraminic acid is deficient, and Forssman glycolipid, which is not present in nervous tissue, failed to produce any significant increase in both SCG and NG not only in amino acid uptake, but also in Na+, K+-ATPase activity. A kinetic study of active AIB uptake showed that GM1 ganglioside produced an increase in Km with no change in Vmax in SCG, whereas it caused a decrease in Km with a slight increase in Vmax in NG. Treatment of NG and SCG with neuraminidase from Vibrio cholerae, an enzyme that split off sialic acid from polysialoganglioside, leaving GM1 intact, caused little inhibition of the amino acid uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Retrograde transport of endogenous nerve growth factor in superior cervical ganglion of adult rats.

The concentration of naturally synthesized nerve growth factor (NGF) was measured in various tissues of adult rats, using a highly sensitive two-site enzyme immunoassay. The highest concentration was found in the superior cervical sympathetic ganglion (SCG). Transection of the postganglionic external carotid nerve (ECN) reduced the ganglionic level of NGF more than did section of the internal carotid nerve (ICN). When both the preganglionic nerve and the ECN were cut, the ganglionic NGF level decreased even more. On the other hand, when the preganglionic nerve and the ICN were both sectioned, leaving the ECN intact, endogenous NGF content in the SCG was significantly enhanced 3-9 h after operation. Bilateral extirpation of submaxillary gland produced a rapid decrease in ganglionic NGF 3-6 h after operation, and even unilateral removal of one salivary gland caused a decrease in both ganglia, which was however much greater in the ipsi- than in the contralateral ganglion. Removal of the eyeballs caused a much smaller reduction in ganglionic NGF than did removal of the glands. These results suggest that the endogenous NGF that accumulates in the SCG is mostly synthesized in the submaxillary gland rather than in the iris, and that it is transported to the SCG, mostly via the ipsilateral ECN.

Animals↗

Effects of extracellular choline concentration and K+ depolarization on choline kinase and choline acetyltransferase activities in superior cervical sympathetic ganglia excised from rats.

The activities of choline kinase (CK) and choline acetyltransferase (ChAT) were examined in vitro in superior cervical sympathetic ganglia (SCG) excised from rats following aerobic incubation for 1 h in a medium containing various choline concentrations, with and without application of a high KCl level (70 mM). Ganglionic CK activity was strongly inhibited (by approximately 75%) at low extracellular choline concentrations (1-5 microM) but rose as the choline concentration was raised to 10-50 microM in the incubation medium, then fell and rose again with further increases in choline concentration. A similar but moderate accelerative effect on ganglionic CK activity was also observed after addition of acetylcholine (ACh; 1 mM) without eserine. Whereas specific CK activity did not change significantly in axotomized SCG, in which the ratio of glial cells to neurons is greatly increased for a week after the operation., it was remarkably increased after denervation, in which the preganglionic cholinergic nerve terminals had degenerated. When either a high KCl level or hemicholinium-3 (HC-3; 50 microM) was added to the medium in the presence or absence of choline, ganglionic CK activity was markedly inhibited. On the other hand, ChAT activity in the SCG remained at a significantly high level during incubation with low choline concentrations (1-10 microM), but the enhanced enzyme activity became inhibited as the extracellular choline concentration was raised to 50-100 microM in the medium. Addition of HC-3 to the medium did not alter ganglionic ChAT activity at low choline concentrations. However, application of quinacrine (10 microM) considerably reduced ganglionic CK activity and also suppressed ChAT activity induced by high KCl levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antipyretic activity of a human immunoglobulin preparation for intravenous use in an experimental model of fever in rabbits.

In an effort to elucidate the reason that fever in patients with severe bacterial infections subsided in some cases after the administration of human immunoglobulin preparations for intravenous use (IGIVs), we focused our attention on the antipyretic activity of IGIVs by investigating experimentally produced pyrexia in rabbits with Escherichia coli-derived lipopolysaccharide (LPS). Although little difference in antibody titers against the antigens composing molecules of LPS was found among the IGIVs that were used, IGIVs treated at pH 4 were demonstrated to inhibit a strongly LPS-induced second-phase febrile response, whereas the inhibitory effect of sulfonated and pepsin-treated IGIVs was weak. In vitro experiments on interleukin-1 production by rabbit macrophages stimulated with LPS, silica gel or latex beads and on rosette formation showed that these functions of the cells were also inhibited by IGIVs. The in vivo antipyretic activity and the results of the two in vitro experiments correlated closely. The inhibitory potency decreased in the following order: immunoglobulin G (IgG) treated at pH4, sulfonated IgG, and pepsin-treated IgG. Thus, it is possible that the subsidence of LPS-induced fever by IGIVs was mediated by inhibition of interleukin 1 production by means of binding of IgG to macrophages via an Fc receptor. Results of this study also indicated the importance of the structural integrity of the Fc portion of the IgG contained in the IGIVs to bind with its receptor on the macrophage so as to influence the various functions carried out by the cell.

Animals↗

T cell factors involved in the regulation of the IgE synthesis.

The IgE-potentiating and IgE-suppressive factors share a common structural gene and therefore a common polypeptide chain, and their biologic activities are decided by a post-translational glycosylation process. Under physiological conditions, this process is controlled by two T cell factors, i.e., the glycosylation-enhancing factor (GEF) and glycosylation-inhibiting factor (GIF). GIF is a fragment of phosphorylated lipocortin and has immunosuppressive effects. Repeated injections of this lymphokine into antigen-primed mice switched their T cells from the formation of IgE-potentiating factor to the formation of IgE-suppressive factor and facilitated the generation of antigen-specific suppressor T cells, which form antigen-specific GIF upon antigenic stimulation. The antigen-specific GIF suppressed the antibody response in a carrier-specific manner and has properties similar to antigen-specific suppressor T cell factors.

Animals↗

Studies on orally active cephalosporin esters.

The synthesis and the biological properties of orally active cephalosporin esters are described. 3-Methoxymethyl cephem derivatives having a 2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamide function at C-7 (1) showed good activity against a wide variety of bacteria including some beta-lactamase producing species. The prodrug type esters of 1 exhibited a good urinary recovery after oral administration to mice and 1-(isopropoxycarbonyloxy)ethyl ester (2a, CS-807) has been pre-clinically tested as an orally active cephem prodrug.

Administration, Oral↗

Double-layered stick-type formulation of bleomycin for treatment of uterine cervical cancer.

The possibility of continuous release over one week of drugs applied topically was investigated using new stick-type formulations of Brilliant Blue (BB) or bleomycin hydrochloride (BLM). Double-layered sticks of BB or BLM able to adhere to mucosa were prepared by direct compression of the drug, hydroxypropylcellulose-H (HPC) and a carboxyvinyl polymer (Carbopol 934). Drug release in vitro from the sticks was delayed by increasing the weight of the outer layer or the amount of HPC in the outer layer. The sustained release achieved with a double-layered stick having a core coated with an acrylate copolymer (MPM) suggests the possibility of once-a-week treatment of uterine cervical cancer.

Benzenesulfonates↗