Significant chemo- and regioselectivies in the Ru(II)-catalyzed [2+2+2] cycloaddition of 1,6-diynes with dicyanides.
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Letter↗
Biomedical subjects
R Ogawa
Publications and source records attributed to R Ogawa.
Intra-bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice.
Intractable autoimmune diseases in chimeric resistant MRL/lpr mice were treated by a new bone marrow transplantation (BMT) method consisting of fractionated irradiation, 5.5 Gy x 2, followed by intra-bone marrow (IBM) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice (5.5 Gy x 2 + IBM). In MRL/lpr mice treated with this method, the number of donor-derived cells in the bone marrow, spleen, and liver rapidly increased (almost 100% donor-derived cells by 14 days after the treatment), and the number of donor-derived hemopoietic progenitor cells concomitantly increased. Furthermore, donor-derived stromal cells were clearly detected in the cultured bone pieces from MRL/lpr mice treated with 5.5 Gy x 2 + IBM. All the recipients thus treated survived more than 1 year (> 60 weeks after birth) and remained free from autoimmune diseases. Autoantibodies decreased to almost normal levels, and abnormal T cells (Thy1.2(+)/B220(+)/CD4(-)/CD8(-)) disappeared. Hematolymphoid cells were reconstituted with donor-derived cells, and newly developed T cells were tolerant to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex determinants. Successful cooperation was achieved among T cells, B cells, and antigen-presenting cells when evaluated by in vitro antisheep red blood cell responses. These findings clearly indicate that this new strategy (IBM-BMT) creates the appropriate hemopoietic environment for the early recovery of hemopoiesis and donor cell engraftment, resulting in the complete amelioration of intractable autoimmune diseases in chimeric resistant MRL/lpr mice without recourse to immunosuppressants. This strategy would therefore be suitable for human therapy.
Animals↗
Comparison of control of Listeria by nitric oxide redox chemistry from murine macrophages and NO donors: insights into listeriocidal activity of oxidative and nitrosative stress.
The physiological function of nitric oxide (NO) in the defense against pathogens is multifaceted. The exact chemistry by which NO combats intracellular pathogens such as Listeria monocytogenes is yet unresolved. We examined the effects of NO exposure, either delivered by NO donors or generated in situ within ANA-1 murine macrophages, on L. monocytogenes growth. Production of NO by the two NONOate compounds PAPA/NO (NH2(C3H6)(N[N(O)NO]C3H7) and DEA/NO (Na(C2H5)2N[N(O)NO]) resulted in L. monocytogenes cytostasis with minimal cytotoxicity. Reactive oxygen species generated from xanthine oxidase/hypoxanthine were neither bactericidal nor cytostatic and did not alter the action of NO. L. monocytogenes growth was also suppressed upon internalization into ANA-1 murine macrophages primed with interferon-gamma (INF-gamma) + tumor necrosis factor-alpha (TNF-alpha or INF-gamma + lipid polysaccharide (LPS). Growth suppression correlated with nitrite formation and nitrosation of 2,3-diaminonaphthalene elicited by stimulated murine macrophages. This nitrosative chemistry was not dependent upon nor mediated by interaction with reactive oxygen species (ROS), but resulted solely from NO and intermediates related to nitrosative stress. The role of nitrosation in controlling L. monocytogenes was further examined by monitoring the effects of exposure to NO on an important virulence factor, Listeriolysin O, which was inhibited under nitrosative conditions. These results suggest that nitrosative stress mediated by macrophages is an important component of the immunological arsenal in controlling L. monocytogenes infections.
2-Naphthylamine↗
Syntheses of two deacetyl-thymosin beta4 analogs and their anti-inflammatory effect on carrageenin-induced edema in the mouse paw.
Two [Met(0)6]deacetyl-thymosin beta4 analogs containing Phe(4F) or Tyr(Me) at position 12 were synthesized by the manual solid-phase method, and their anti-inflammatory effect on carrageenin-induced edema in the mouse paw was studied. Fluorination of the para-position of Phe12 resulted in a marked antiinflammatory effect on carrageenin-induced edema in the mouse paw compared with that of our synthetic [Met(0)6]deacetyl-thymosin beta4, but the other analog, [Met(0)6, Tyr(Me)12]deacetyl-thymosin beta4, showed a marked reduction of the anti-inflammatory effect.
Animals↗
T lymphocyte activation and restenosis after percutaneous transluminal coronary angioplasty.
We investigated the relation between the activation of T lymphocytes and the occurrence of restenosis after percutaneous transluminal coronary angioplasty (PTCA) in 10 stable angina patients. Recent studies have suggested that PTCA causes an inflammatory response, which may affect restenosis after angioplasty. Soluble interleukin-2 receptor (sIL-2R) is a useful marker to evaluate the activation of T lymphocytes. sIL-2R was measured before and 2 h after successful PTCA, and 3-month follow-up coronary angiography was done to observe restenosis. Four of 10 patients showed restenosis. The restenosis group of 4 patients had a higher level of sIL-2R after PTCA than the no-restenosis group of 6 patients (495 vs. 274 U/ml, p < 0.01). This study suggests that sIL-2R may offer prognostic information after elective PTCA and identify a subgroup of patients at high risk for clinical restenosis in a few months.
Aged↗
The effects of diltiazem on hemodynamics and seizure duration during electroconvulsive therapy.
UNLABELLED: Electroconvulsive therapy (ECT) is often associated with acute hyperdynamic responses, and we hypothesize that diltiazem can blunt this response. We measured the effect of a 10-mg dose of diltiazem on heart rate and mean arterial pressure during ECT. Furthermore, we assessed seizure duration by using both the cuff method and two-lead electroencephalogram. We studied 18 patients with a randomized, double-blinded, placebo-controlled cross-over study design. Diltiazem significantly reduced heart rate and mean arterial pressure just after medication, and it also significantly reduced the increases in these variables after ECT, as compared with the placebo. The use of diltiazem was, however, associated with a shortened seizure duration, possibly making ECT less effective. Because of the reduction in seizure duration, the routine administration of diltiazem may not be advisable because it can possibly interfere with the psychotherapeutic efficacy of ECT. However, diltiazem medication for ECT is potentially useful for reducing tachycardia and hypertension in high-risk patients. IMPLICATIONS: Diltiazem can blunt acute hyperdynamic responses after electroconvulsive therapy, but seizure duration is also significantly reduced, possibly making this therapy less effective.
Adult↗
Molecular mechanisms for alpha2-adrenoceptor-mediated regulation of synoviocyte populations.
The sympathetic nervous system has been indicated to influence the severity of inflammatory disease including rheumatoid arthritis. In this study, we elucidated the effects of catecholamine on the synovial cell populations. Stimulation with epinephrine or norepinephrine for 1-2 weeks dose- and time-dependently increased the number of synovial A (macrophage-like) cells but decreased that of B (fibroblast-like) cells. These responses in A and B cells were inhibited by the alpha2-antagonist yohimbine, the G-protein inactivator pertussis toxin and the phospholipase C (PLC) inhibitor U-73122. Furthermore, the protein kinase C (PKC) inhibitor calphostin C and mitogen-activated protein (MAP) kinase inhibitors PD98059 and wortmannin also abolished the norepinephrine effects on A and B cell numbers. In A cells cloned from an A and B cell mixture, norepinephrine also increased the cell number. In immunoblotting and immunocytostaining analyses, among the PKC isozymes, only PKC betaII immunoreactivity was observed in the cytoplasm of unstimulated A and B cells. After alpha2-adrenoceptor stimulation, PKC betaII immunoreactivity increased in the plasma membranes of both A and B cells with decreases in the cytoplasm. These findings indicated that alpha2-adrenoceptor stimulation of type A and B synoviocytes produced an increase and a decrease in the respective cell number, probably through Gi-coupled PLC activation and the resulting stimulation of the PKC betaII/MAP kinase.
Adrenergic alpha-Agonists↗
Activation of the adenosine triphosphate sensitive mitochondrial potassium channel is involved in the cardioprotective effect of isoflurane.
The adenosine triphosphate-dependent potassium (K(ATP)) channel has been proposed to play an important role in the cardioprotective effect of isoflurane (ISO). However, the question of whether the K(ATP) channel, sarcolemmal or mitochondrial is the main contributor to the effect has not been clarified. The major aim of the present study was to determine whether or not the mitochondrial potassium channel was a site of action for ISO. Whether there was an acute "memory phase", in which drugs were not detected in the tissues, but the protective effect still remained in the ischemic preconditioning (IP) -like effect of ISO was also investigated. Dangling participle isolated rat hearts, a 20-min normothermic nonperfused phase was maintained to produce a global ischemia. Under these ischemic conditions, the effects of ISO, sodium 5-hydroxydecanoate (5HD: a selective mitochondrial K(ATP) channel antagonist), and ISO combined with 5HD on cardiac performance were examined. To all these four groups, (non-treated group, ISO group, 5HD group and ISO plus 5HD group, n=6 each) drugs were given for 30 min. After 10 min of drug-free perfusion (pre-ischemia restabilization period), 20 min of ischemia followed. Then the cardiac performance and the creatine kinase (CK) release during the reperfusion period were tested. In the non treated group and 5HD group, cardiac performance was stable during the treated period and pre-ischemia the restabilization period. In the ISO group and ISO plus 5HD group, heart rate (HR), left ventricular (LV) systolic pressure, and LV maximum rate of development of tension (dP/dtMax) during the drug-treated period became gradually and linearly worse. However, these values were the same as in the non-treated group and 5HD group at the end of the pre-ischemia restabilization period. So 5HD itself had no hemodynamic effect; nor did it have any influence on the actions of ISO. At the end of the pre-ischemia restabilization period, the significant hemodynamic differences among the groups diminished and ISO was not detected in the solution. In the post-reperfusion period, except for the ISO group, (non treated group, 5HD group and ISO plus 5HD group) cardiac performances were drastically decreased. ISO significantly ameliorated the dysfunction of cardiac output, LV systolic pressure and LV+dP/dtMax. The CK level in the coronary effluent during reperfusion was also significantly reduced by ISO. 5HD completely inhibited these cardiac effects of ISO. Activation of the adenosine triphosphate sensitive mitochondrial potassium channel is involved in the cardioprotective effect of ISO, and the action of this agent has an acute"memory phase" like ischemic preconditioning.
Adenosine Triphosphate↗
von Recklinghausen disease complicated by pulmonary hypertension.
Two patients with von Recklinghausen disease (neurofibromatosis type 1) were admitted to the hospital because of progressive heart failure. Both patients had prominent pulmonary hypertension revealed on cardiac catheterization. A lung perfusion scan did not show any gross defect. There were no underlying causes of pulmonary hypertension in either patient, such as chronic lung disease, congenital or acquired heart disease, deep vein thrombosis, or systemic hypercoagulable states. There may be an unrecognized association between von Recklinghausen disease and pulmonary hypertension.
Adult↗
Crucial role of donor-derived stromal cells in successful treatment for intractable autoimmune diseases in mrl/lpr mice by bmt via portal vein.
We have recently established a new bone marrow transplantation (BMT) method for the treatment of intractable autoimmune diseases in MRL/lpr mice; the method consists of fractionated irradiation (5.5 Gy x 2), followed by BMT of whole bone marrow cells (BMCs) from allogeneic C57BL/6 mice via the portal vein (abbreviated as 5.5 Gy x 2 + PV). In the present study, we investigate the mechanisms underlying the early engraftment of donor-derived cells in MRL/lpr mice by this method. In the mice treated with this method, the number of donor-derived cells possessing the mature lineage (Lin) markers rapidly increased in the BM, spleen, and liver; almost 100% were donor-derived cells by 14 days after the treatment. The number of donor-derived hemopoietic progenitor cells (defined as c-kit(+)/Lin(-) cells) increased in the BMCs, hepatic mononuclear cells, and especially spleen cells by 14 days after the treatment. Simultaneously, hemopoietic foci adjoining donor-derived stromal cells were observed in the liver when injected via the PV, but not via the peripheral vein (i.v.). When adherent cell-depleted BMCs were injected via the PV, recipients showed a marked reduction in the survival rate. However, when mice were transplanted with adherent cell-depleted BMCs with cultured stromal cells, all the recipients survived. These findings suggest that not only donor hematopoietic stem cells (HSCs) but also donor stromal cells administered via the PV were trapped in the liver, resulting in the early engraftment of donor HSCs in cooperation with donor-derived stromal cells. This new strategy to facilitate the early recovery of hemopoiesis would therefore be of great advantage in human application.
Animals↗
Serum levels of interleukin 6 and stress related substances indicate mental stress condition in patients with rheumatoid arthritis.
OBJECTIVE: To evaluate the influence of mental stress on the neuroendocrine-immune system in patients with rheumatoid arthritis (RA). METHODS: Twenty-two patients with RA and 8 patients with osteoarthritis (OA) who underwent total knee or hip arthroplasties under general anesthesia were enrolled in the study. The blood levels of interleukin 6 (IL-6) and other substances related to stress were measured just before administering anesthesia on the day of the operation when the patients lay on the operating table and roughly 30 min later when the patients were under general anesthesia without mental stress. These values were compared with those at the same time on the day before the operation, which were considered the control levels. RESULTS: In patients with RA, the levels of IL-6, cortisol, and epinephrine in the peripheral blood were significantly increased under mental stress, before anesthesia (p < 0.01). However, under general anesthesia, the IL-6, cortisol, and epinephrine were significantly decreased, compared with the levels before anesthesia (p < 0.01). Such changes were not apparent in patients with OA. The levels of other substances in the peripheral blood known to be related to stress, such as corticotropin-releasing factor, dopamine, and norepinephrine, showed no changes in patients with RA or OA. CONCLUSION: In patients with RA, excessive mental stress should be eliminated to modify the interaction between the stress-immune system and stress-endocrine system as a method to better control disease activity.
Aged↗
Lean body mass and body fat distribution in participants with chronic low back pain.
BACKGROUND: Loss of muscle mass and central obesity progress with aging, but the effect of muscle loss on chronic low back pain has not been precisely evaluated. METHODS: Three hundred thirty Japanese persons aged 45 to 69 years, with a complaint of low back pain for longer than 3 months (n = 203) and age- and sex-matched healthy control subjects (n = 127), were enrolled in this study. Participants with chronic low back pain were classified into the following groups: (1) women with a positive straight leg raise test result, (2) women with a negative straight leg raise test result, (3) men with a positive straight leg raise test result, and (4) men with a negative straight leg raise test result. Controls were classified by sex into a female and a male group. Anthropometric data, consisting of body mass index, percentage body fat, waist-hip ratio, and lean body mass of the upper extremities, trunk, and lower extremities divided by body weight, were measured in participants with low back pain, and the results were compared with those of controls. RESULTS: The waist-hip ratio in women with a negative straight leg raise test result was significantly higher than those in the female control group (P<.001) and in the women with a positive straight leg raise test result (P =.04). The lean body mass of the trunk and lower extremities divided by body weight of women with a negative straight leg raise test result was significantly lower than that of female controls (P =.03 for the trunk and P<.001 for the lower extremities). However, no significant differences were detected between the female negative straight leg raise test result group and the female control group for lean body mass of the upper extremities divided by body weight or body mass index. There were no significant differences in anthropometric data between the male test and control groups or between the female positive straight leg raise test result group and the female control group. CONCLUSION: Trunk and lower extremity loss of muscle mass and central obesity may be risk factors for chronic low back pain without a positive straight leg raise test result in women aged 45 to 69 years. Arch Intern Med. 2000;160:3265-3269.
Adipose Tissue↗
Treatment of intractable autoimmune diseases in MRL/lpr mice using a new strategy for allogeneic bone marrow transplantation.
A new bone marrow transplantation (BMT) method for treating severe autoimmune diseases in chimeric resistant MRL/lpr mice is presented. The method consists of fractionated irradiation (5.5 Gy x 2), followed by portal venous (PV) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice and intravenous (IV) injection of whole B6 BMCs 5 days after the PV injection (abbreviated as 5.5 Gy x 2 + PV + IV). All recipients survived more than 1 year after this treatment (more than 64 weeks after birth). Abnormal T cells (Thy1.2(+)/B220(+)/CD3(+)/CD4(-)/CD8(-)) present in MRL/lpr mice before the treatment disappear, and hematolymphoid cells are reconstituted with donor-derived cells. The treated mice are free from autoimmune diseases. Levels of autoantibodies (IgG/IgM anti-ssDNA antibodies and IgG/IgM rheumatoid factors) decrease to normal levels. Successful cooperation is achieved among T cells, B cells, and antigen-presenting cells (APCs) of the treated MRL/lpr mice when evaluated by in vitro anti-SRBC responses. Newly developed T cells are tolerant to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex (MHC) determinants. These findings clearly indicate that severe autoimmune diseases in MRL/lpr mice are completely ameliorated by the treatment without recourse to immunosuppressants, and that the treated MRL/lpr mice show normal immune functions, strongly suggesting that this strategy would be applicable to humans. (Blood. 2000;95:1862-1868)
Animals↗
Control engineering and electromyographic kinesiology analyses of normal human gait.
In this study, we analyzed the electrical activity patterns of the antagonistic bi-articular and mono-articular muscles of both legs during normal gait cycles, in terms of electromyographic (EMG) kinesiology and control engineering. For control engineering analyses, we utilized a mechanical two-joint link model equipped with antagonistic pairs of bi-articular and mono-articular muscles. It was confirmed that the coordinated activity pattern, in which the bi-articular muscles of the rectus femoris (Rf) and the medial hamstrings (Mh) showed criss-cross EMG patterns, and the mono-articular muscles of the gluteus maximus and the vastus medialis showed sustained activities during the early stance phase in the gait cycle, contributed to the output force control and the output force direction control. Reversal of Rf and Mh activities was responsible for changes in the output force direction during the heel contact period. The results obtained here strongly highlight the importance of and necessity for control engineering evaluation of coordinated muscle activities of bi-articular and mono-articular antagonistic muscles for analyses not only of gait but also of sports injuries.
Adolescent↗
Biomechanical study of gait using an intelligent brace.
We have developed a new long leg brace fitted with a computer-controlled knee joint that allows the user to go up and down a slope and stairs. Using this new brace, we analyzed gait under various conditions in ten normal men in terms of dynamic electromyography. Walking up a slope with normal step produced discharges in the leg muscles other than the gastrocnemius lateral head before and after the heel-strike on the ground, which indicated the absorption of the impact of landing. Going down a slope with controlled step resulted in lower activities of the tibialis anterior and the gastrocnemius lateral head than doing so with non-locked step or locked step. In subjects walking up stairs with tandem gait, the large discharges of the gastrocnemius lateral head that were observed in the late stance phase with normal step disappeared when the brace was applied. These results indicated that the muscle activity levels decreased during controlled walking with this new brace, and that the new brace can compensate for reduced muscle strength of the lower leg during walking. Kinematic analysis of walking revealed no significant difference between normal walking and controlled walking under any walking conditions.
Adult↗
Minor cardiac troponin T release in patients undergoing coronary artery bypass graft surgery on a beating heart.
OBJECTIVES: To determine whether and to what extent coronary artery bypass graft (CABG) surgery without extracorporeal circulation is associated with cardiac troponin T (TnT) release. DESIGN: Prospective study. SETTING: A single university hospital. PARTICIPANTS: Twenty-three patients scheduled for minimally invasive CABG surgery. Sixteen patients received one coronary anastomosis, and seven received two. INTERVENTIONS: TnT and creatine kinase-MB (CK-MB) levels were determined immediately before induction of anesthesia (baseline) and at 0, 12, and 24 hours after surgery. Hemodynamic measurements were made, and 5-lead electrocardiograms with continuous automated ST-segment trends were analyzed. MEASUREMENTS AND MAIN RESULTS: All patients had a good cardiac outcome. Median cumulative coronary artery occlusion time was 27 minutes (range, 10 to 49 minutes). TnT levels were undetectable in 91.3% of patients at baseline when a detection limit of 0.01 ng/mL was employed. TnT and CK-MB showed significant elevations at 12 and 24 hours versus baseline. Postoperatively, TnT was detectable in 91.3% of patients, and 17.4% suffered minor myocardial damage, as evidenced by an abnormal increase in TnT greater than 0.2 ng/mL, excluding those exhibiting myocardial infarction. ST segment changes developed in seven patients, persisting for 13.0 minutes (range, 9.5 to 15.8 minutes) and disappearing immediately after coronary artery clamp release. There were no significant correlations between cumulative coronary occlusion time and peak TnT or CK-MB levels. CONCLUSIONS: TnT was detected after surgery in most patients, and significant TnT levels indicative of myocardial injury (>0.2 ng/mL) were detected in only 17% of patients, probably as a result of brief periods of coronary artery occlusion.
Adult↗
Suppression of surgical hyperaldosteronism by potassium canrenoate during gynecologic surgery under sevoflurane anesthesia.
BACKGROUND: Surgical hyperaldosteronism leads to sodium and water retention during surgery and often causes postoperative edema. This study investigated the effect of potassium canrenoate (PC) on pituitary adrenocortical function in lower abdominal surgery under sevoflurane anesthesia. METHODS: Twenty patients were randomized to receive 400 mg of PC (the PC group, n=10) or saline (the control group, n=10) intravenously. The following parameters were determined: plasma aldosterone, adrenocorticotropic hormone (ACTH), plasma renin activity (PRA), serum sodium and potassium, urinary sodium and potassium, and urine output. RESULTS: The aldosterone and ACTH levels showed significant increases in the control group during surgery. Plasma ACTH also increased significantly in the PC group, but plasma aldosterone levels were unchanged during surgery. The urine Na/K ratio of the PC group was significantly higher than that of the control group. CONCLUSION: The present study suggested that PC suppresses the increase of plasma aldosterone caused by surgical stress. That may prevent sodium retention and potassium excretion during surgery.
Adrenocorticotropic Hormone↗
Role of inflammatory mediators in lipid A analogue (ONO-4007)-induced vascular permeability change in mouse skin.
1. Endotoxin shock is accompanied by an increase in peripheral vascular permeability. It has been postulated that most biological activities of LPS are derived from lipid A moiety. Here we examined the effect of lipid A analogue ONO-4007 in increasing vascular permeability and the possible mediators in mouse skin by a dye leakage method. 2. Subcutaneous injection of ONO-4007 (1 - 2 mg site(-1)) induced a dose-dependent increase in vascular permeability which was evident after 120 min. 3. ONO-4007-induced dye leakage was significantly attenuated by pretreatments with anti-tumour necrosis factor-alpha (TNF-alpha) and anti-interleukin-1alpha (IL-1alpha) antibodies, but not with indomethacin (5 mg kg(-1)) or diphenhydramine (10 mg kg(-1)). ONO-4007-induced dye leakage was significantly inhibited by a pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) (10 mg kg(-1)) but not with aminoguanidine (50 mg kg(-1)). In inducible nitric oxide synthase (iNOS)-deficient mice, ONO-4007 significantly increased the dye leakage, while ONO-4007 dilated rat thoracic aortic rings pre-contracted with phenylephrine, and the L-NAME pretreatment inhibited the dilation. 4. Thus, TNF-alpha, IL-1alpha and constitutive NOSs-derived nitric oxide but not prostaglandins or histamine play a role in ONO-4007-induced increase in vascular permeability. Although ONO-4007 mimics LPS in increasing vascular permeability, mechanisms of permeability change elicited by ONO-4007 were not identical to those of LPS.
Animals↗