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Biomedical subjects

R Mori

Publications and source records attributed to R Mori.

At least 127 records · Page 7Linked to original sources

Participation of T lymphocyte in corneal edema in the early stage of herpetic stromal keratitis.

The participation of T lymphocytes in the immunopathogenesis of corneal opacity in herpetic stromal keratitis was investigated. In BALB/c mice infected intracorneally with herpes simplex virus type 1, corneal opacity was manifested 10 days after infection, while in athymic mice corneas remained almost clear. Histologically, all opaque corneas revealed stromal edema accompanied by the diffuse presence of polymorphonuclear cells and lymphocytes. When complement (C')-treated immune spleen cells were adoptively transferred into athymic mice 6 or 72 h after corneal infection, stromal keratitis with mild opacity was observed 10 days after transfer. The athymic mice given anti-Thy 1.2+C'-treated immune spleen cells failed to develop corneal opacity. The difference, as revealed by light and electron microscopy, was the presence or absence of lymphocytic infiltration and edema in the posterior third layers of the stroma and endothelial lesions. The endothelium was infiltrated by lymphocytes or macrophages and showed various stages of destruction. The main cause of corneal opacity in the early stage of herpetic stromal keratitis is thought to be stromal edema due to an adverse effect on the endothelium by immune T lymphocytes.

Animals↗

Different mechanisms of the rabbit pulmonary arterial contraction caused by 5- or 6-hydroxydopamine.

The contractile responses of rabbit arterial strips to 5-hydroxydopamine (5-OHDA) or 6-hydroxydopamine (6-OHDA) were assessed in vitro. The 3H efflux from the pulmonary artery after preloading with [3H]noradrenaline was markedly enhanced by 100 microM 5-OHDA or 6-OHDA. In non-superfused strips, 6-OHDA produced a biphasic contraction, an initial small transient and a subsequent large sustained contraction, whereas 5-OHDA elicited a large monophasic contraction. The 6-OHDA-evoked second large contraction was followed by a marked tachyphylaxis after repeated application of the drug. This contraction was greatly diminished by prazosin or cocaine and by pretreatment with reserpine, indicating an indirect action via noradrenaline release. In contrast, the initial contraction caused by 6-OHDA as well as the contraction caused by 5-OHDA was not inhibited by these agents, except prazosin, implying a direct action at the postsynaptic alpha 1-adrenoceptors. In addition, the concentration-response curve for noradrenaline was significantly shifted to the right by pre-addition of 5-OHDA whereas the curve for 5-HT was virtually unaffected. The results thus suggest that 5-OHDA acts as a postsynaptic alpha 1-adrenoceptor agonist.

Animals↗

The effects of ultraviolet irradiation of the skin on herpes simplex virus infection: alteration in immune function mediated by epidermal cells and in the course of infection.

Previously, we demonstrated that Ia+ epidermal cells (EC) have herpes simplex virus (HSV) antigen-presenting capacity in vitro and play an important role in resistance to HSV infection in vivo. In the present study, we investigated the effects of in vivo ultraviolet (UV) irradiation of the skin on the HSV-immunity function of EC both in vitro and in vivo and on the pathogenesis of HSV infection. Immune T cells cultured with EC and HSV antigen showed a proliferative response in vitro. Exposure of the skin to UV light 1 to 3 days before preparation of EC resulted in dose-dependent impairment of this proliferation. This UV-induced impairment of the accessory cell function of EC was accompanied by a parallel reduction of the number of Ia+ EC. We also transferred these EC-stimulated T cells to intracutaneously infected nude mice. Immune T cells stimulated with EC obtained from irradiated mice did not effectively clear HSV and allowed development of zosteriform skin lesions. In contrast normal-EC-stimulated immune T cells completely prevented the formation of a zosteriform rash. In addition, mice irradiated with UV on shaved midflank skin 2 days before intracutaneous inoculation of HSV showed increased severity of infection and a higher incidence of latency compared with control mice. These studies indicate that in vivo UV irradiation of the skin abrogates the immune function of EC both in vitro and in vivo, and affects HSV pathogenesis. The implication of our results for the better understanding of the effect of UV on acute and recurrent HSV infections is discussed.

Animals↗

Experimental allergic encephalomyelitis in the Lewis rat. A model of predictable relapse by cyclophosphamide.

Relapse of experimental allergic encephalomyelitis (EAE) was achieved in Lewis rats by cyclophosphamide (CY). All rats, immunized with an emulsion of guinea pig spinal cord homogenate in complete Freund's adjuvant and treated with 100 mg/kg of CY 21 days postimmunization (pi), developed moderate to severe paralysis 9-14 days following CY injection. A second relapse was observed in 4 of 11 rats reinjected with CY 49 days pi. Histologically, focal mononuclear cell infiltration with or without demyelination of the white matter of the central nervous system was observed. Cyclophosphamide administration caused transient leukopenia and T-cell defect, the resolution of which coincided with relapse of clinical EAE. Lymphocyte proliferative responses to myelin basic protein (BP) and concanavalin A (Con A) and antibody titers to BP were preserved in CY-treated rats. Adoptive transfer of EAE to naive recipients with Con A-activated spleen cells from donors with CY-induced relapse was unsuccessful.

Animals↗

Protection against herpes simplex virus infection in mice by recombinant murine interferon-beta in combination with antibody.

A recombinant murine interferon -beta (rMuIFN-beta) was used to suppress the development of skin lesions and death of mice after challenge with herpes simplex virus (HSV) type 1 (HSV-1). Depilated female BALB/c mice were inoculated intradermally with HSV-1, Hayashida strain, and were administered various concentrations of interferon (IFN) intraperitoneally 3 h later. The treatment with IFN was given once a day for 10 successive days. Under the conditions in which almost all control mice died after development of severe zosteriform skin lesions, the mortality of mice treated with IFN (8 X 10(5) or 8 X 10(4) U/mouse) was less than 50% (9/20 and 4/10, respectively), though all mice treated with a lower dose of IFN (8 X 10(3) U/mouse) died. Titration revealed that there was no significant suppression of virus growth by IFN in the skin or dorsal root ganglia, but it was significantly suppressed in the brain. The protective effect of IFN was enhanced when it was used in combination with human anti-HSV antibody having a neutralizing titer (NT) of 1:16. All mice treated with IFN (8 X 10(5) U/mouse) and antibody (NT, 1:16) survived, and only 40% of them developed slight zosteriform skin lesions. The effect of the combination was observed even when both IFN and antibody were diluted 1:10. The protective effect of IFN was also observed when athymic nude mice were used as the host. In this system, though the IFN-treated nude mice survived significantly longer than the controls, they finally died. In antibody- or acyclovir (ACV)-treated nude mice, there was also a prolongation of survival time as compared with control mice. The effect of antibody was enhanced by the addition of IFN, but IFN did not potentiate the effect of ACV.

Animals↗

Protective effect of recombinant murine interferon beta against mouse hepatitis virus infection.

Recombinant murine interferon beta (rMuIFN-beta) protected susceptible C57BL/6 mice against lethal mouse hepatitis virus (MHV) infection. rMuIFN-beta was life saving if it was given intraperitoneally beginning 21 h before infection and daily thereafter for 9 days, and lengthened the survival time if given from 3 h after infection. rMuIFN-beta treatment beginning 24 h after infection was ineffective. The survival rate was dose-dependent, and the 50% effective dose of rMuIFN-beta for survival was 1780 IU per day. rMuIFN-beta pretreatment inhibited virus growth completely in the brain and moderately in the liver and spleen and prevented severe hepatic lesions. rMuIFN-beta also protected beige mice and cyclophosphamide-treated mice against MHV infection, suggesting that activation of natural killer cells or T-cells by rMuIFN-beta is not critical for protection.

Animals↗

Release of purines and noradrenaline from the vascular adrenergic nerves by 5- and 6-hydroxydopamine.

1. The in vitro effects of 6-hydroxydopamine (6-OHDA) and 5-hydroxydopamine (5-OHDA) on 3H-efflux from rabbit pulmonary artery after incubation with [3H]noradrenaline ([3H]NA) or [3H]adenosine were assessed. 2. 6-OHDA (100 microM) or 5-OHDA (100 microM) enhanced not only [3H]noradrenaline efflux, but also [3H]purines efflux. 3. Following Ca2+-removal, [3H]NA and [3H]purine effluxes evoked by these hydroxydopamines were moderately and considerably diminished, respectively. In addition, the 6-OHDA-evoked [3H]purine efflux was significantly decreased by W-7 (30 microM), a calmodulin inhibitor. 4. The 6-OHDA or 5-OHDA-evoked purine release was almost insensitive for prazosin (0.3 microM), indicating a neuronal release. 5. The peak [3H]purine efflux evoked by 6-OHDA or 5-OHDA occurred in the corresponding fraction number to that for the [3H]NA efflux. 6. These results suggest that 6-OHDA and 5-OHDA may expel NA together with purines from the amine stored sites (probably, in axoplasm) in the adrenergic nerves.

Adenosine↗

Antiviral activities of human monoclonal antibodies to herpes simplex virus.

Hybridomas producing human monoclonal antibodies (MAbs) against herpes simplex virus (HSV) were established by fusing human tonsillar lymphocytes with mouse myeloma cells. Three hybridomas have been stably producing MAbs for more than 16 months. All three MAbs--H1, H2, and H3--were of the IgG1 isotype and recognized the gB glycoprotein of HSV types 1 and 2 (HSV-1 and HSV-2). MAbs H2 and H3 not only bound to the surface membrane of HSV-infected cells but also neutralized both HSV-1 and HSV-2, whereas MAb H1 had neither activity. In mouse infection experiments, MAbs H2 and H3 showed a potent protective effect against HSV-1 infection, whereas MAB H1 was less protective. Furthermore, the development of zosteriform skin lesions in athymic nude mice was suppressed by administering MAb H2. These results suggest that human MAbs might provide passive immunization against HSV infections in humans.

Animals↗

Reverse-flow island flap: clinical report and venous drainage.

Twenty-two reverse-flow island flaps were transferred. These included peroneal, forearm, anterior tibial, and temporal flaps. Sixteen of 22 flaps survived completely. We encountered partial necrosis in 4 flaps and total necrosis in only 2 flaps. We credit this success to the reliability and availability of the peroneal, forearm, and temporal flaps; but we do not encourage use of the anterior tibial flap. The flaps that survived well did not show any signs of venous congestion. The advantage of the reverse-flow island flap is that it can be transferred from a proximal to a distal location. Using cadavers and fresh amputated limbs, studies on venous drainage of the reverse-flow island flap were performed. The venae comitantes had numerous venous valves and communicating branches, but more than sufficient reflux of the venous blood occurred through the valves at pressures of 90 to 105 cmH2O. We believe that the venous drainage of the reverse-flow island flap occurs as a result of reflux actions at the valve, communicating branches between the venae comitantes, and bypass vessels around the valves.

Adult↗

Pharmacological effects of the antianxiety compound suriclone and its principal metabolites.

The pharmacodynamic effects of 4-methyl-1-piperazinecarboxylic acid ester with (+/-)-6-(7-chloro-1,8-naphthyridin-2-yl)-2,3,6,7-tetrahydro-7-h ydr oxy-5H-p- dithiino[2,3-c]pyrrol-5-one (suriclone, RP-31264) and its principal metabolites M1 and M2 on respiration, cardiovascular system, autonomic nervous system, smooth muscle and other physiological parameters were investigated in various animal species. Suriclone, 1 mg/kg i.v., increased the amplitude of respiratory movement, decreased the respiratory rate and blood pressure and increased the heart rate in conscious rabbits. The respiratory and depressor effects were more evident in pentobarbital anesthetized rabbits. In anesthetized dogs, suriclone, 0.05 or 0.5 mg/kg i.v., produced essentially the same effects as seen in the anesthetized rabbits. The ECG pattern was not significantly changed in any animal. Such effects on respiration and on the cardiovascular system of metabolites M1 and M2 in the rabbits were weak. In the isolated guinea-pig atria, suriclone, 10(-6) g/ml, had no effect but increased contractility and decreased heart rate at a high concentration of 10(-5) g/ml. Both M1 and M2 had weak effects. Suriclone had no action on flow rate of the perfusate through the blood vessels of the isolated rabbit ear. In anesthetized dogs, suriclone 0.5 mg/kg i.v., did not affect the responses to vagal stimulation or to pre- and postganglionic stimulation of cardiac ganglion. Suriclone instilled onto the eye or i.v. had no appreciable effect on pupillary diameter or the miotic response in rabbits, but an abnormal oculogyration was evoked when the drug was given i.v. at 1 mg/kg. M1 or M2 had no such effect. Suriclone did not exert analgesic effects in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antithrombin III loss in patients with nephrotic syndrome or receiving continuous ambulatory peritoneal dialysis. Evidence of inactive antithrombin III in urine of patients with nephrotic syndrome.

Antithrombin III (AT III) was measured as antigen (Ag) and as heparin cofactor (HC) in plasma and urine or dialysate from nine patients with nephrotic syndrome and nine patients receiving continuous ambulatory peritoneal dialysis (CAPD), respectively. Crossed immunoelectrophoresis on heparin-agarose (H-CIE) and crossed immunoelectrofocusing (CIEF) runs were carried out on plasma and urine or dialysate samples. AT III plasma levels of the patients receiving CAPD were in the normal range, whereas levels in the patients with nephrotic syndrome showed a significant reduction. Nevertheless the AT III Ag daily loss was the same in both patient groups, so that an additional AT III loss caused by renal metabolism was suggested in patients with nephrotic syndrome. No alteration in the isoantithrombin plasma distribution was found in any patient. The AT III recovered in urine was almost all inactive, as demonstrated by the quantitative assays and by the H-CIE runs; on the contrary, the findings obtained by functional assays, H-CIE, and CIEF runs on dialysate samples failed to demonstrate any major alteration in the AT III molecule. In urine the AT III CIEF pattern displayed a more acid distribution (pH 4.9 to 4.5) in respect to the plasma AT III (pH 5.2 to 4.6); this pattern was suggested to be related to the renal AT III functional inactivation, whose exact mechanism remains to be clarified.

Adult↗

[Morphological and functional study of deep veins in the reverse flow island flap].

Reid and Biemer in 1983 introduced the reverse flow forearm flap and Yoshimura in 1984 reported the reverse flow peroneal flap. No problems were experienced in any of our cases by drainage from valves of the concomitant veins. From our experiments on one cadaver and eight freshly amputated limbs the following comments may be made about the mechanism of drainage in reverse flow in the concomitant vein: Each concomitant vein has many anastomoses and there are resulting by-passes which go around the valves. For that reason, the reflux does not always occur in all valves. It is believed that special valves only in certain parts of the vein are triggered to open when there is a 90-100 cm H2O pressure and at that time reflux occurs.

Arm↗

Immunogenicity of purified glycoprotein gB of herpes simplex virus.

The efficacy of a herpes simplex virus (HSV) component vaccine consisting of viral glycoprotein gB was examined in a mouse system. Immunization of mice with HSV type 1 (HSV-1) gB emulsified in Freund's complete adjuvant or with HSV-1 gB adsorbed to aluminum gel was fully protective against subsequent challenge with HSV-1 or HSV type 2. Latent infection in the trigeminal ganglion was also prevented by immunization with gB.

Animals↗

Role of epidermal Langerhans cells in resistance to herpes simplex virus infection.

To investigate the role of epidermal Langerhans cells (LC) in resistance to herpes simplex virus (HSV) infection, nonadherent spleen cells taken from BALB/c mice immunized with HSV were cultured with syngeneic epidermal cells (EC) and ultraviolet light-inactivated HSV antigen. After five days of culture, T cell-dependent proliferative response was determined by 3H-thymidine incorporation. Treatment of EC with anti-Iad monoclonal antibody plus complement before cultivation prevented this proliferation, which suggested that LC induced stimulation of immune T cells. When these stimulated spleen cells were transferred to intracutaneously infected nude mice, the virus titer in the skin was reduced markedly and the formation of zosteriform skin lesions was completely inhibited. On the other hand, transfer of unstimulated cells, which were cultured with HSV antigen only or with HSV antigen and EC treated with anti-Iad monoclonal antibody plus complement, resulted in delayed viral clearance and development of the lesions. These results indicate that LC are of importance as accessory cells in the control of cutaneous HSV infection. Furthermore, Lyt 1+ T cells in the stimulated population were shown to have greater protective activity than Lyt 2+ T cells.

Animals↗