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Biomedical subjects

J Suzuki

Publications and source records attributed to J Suzuki.

At least 253 records · Page 14Linked to original sources
PubMed1997

[Pharmacological characteristics of the long-acting beta-blocker "bopindolol"].

The non-selective beta-blocker bopindolol, which was developed as a pro-drug, possessed 50-60 times more potent long-acting hypotensive effects on the blood pressure than those of atenolol or propranolol. Because this drug has only a mild partial agonist activity, it did not cause the rapid decrease in heart rate observed with atenolol or propranolol or the increase in heart rate induced by pindolol. These hypotensive effects are due to beta 1-antagonistic effects, not effects on beta 2- or beta 3-adrenoceptors. In addition to these effects, benefits of this drug include the following: slow dissociation rate from beta-adrenoceptors in tissues, high affinity to 5-HT1A subtypes, less clinical effects on lipid metabolism and the inhibition of renin release. It is possible that this drug possesses different pharmacological characteristics from other beta-blockers.

Adrenergic beta-Antagonists↗
PubMed1997

Interleukin-13 but not interleukin-4 prolongs eosinophil survival and induces eosinophil chemotaxis.

The effects of recombinant human (rh) interleukin (IL)-4 or rhIL-13 on survival, and chemotactic activity of human eosinophils were examined. Only rhIL-13 prolonged eosinophil survival in a dose-dependent manner above 3 ng/ml. Eosinophil survival induced by rhIL-13 was inhibited by monoclonal antibodies (mAbs) against IL-3 (p < 0.01) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (p < 0.05), suggesting that rhIL-13 induced IL-3 and GM-CSF production from eosinophils and an autocrine mechanism is responsible for the eosinophil survival. The effects of rhIL-13 on eosinophil chemotactic activity were also examined. rhIL-13 showed chemotactic activity for eosinophils in a dose-dependent manner. Checkerboard analysis revealed that eosinophil migration was dependent on the concentration gradient, confirming that rhIL-13 is a chemotactic factor. rhIL-4 showed no effects. IL-13 may play an important role in the survival and recruitment of eosinophils in allergic diseases.

Cell Degranulation↗
PubMed1997

Inhibitory effects of theophylline and procaterol on eosinophil function.

Eosinophils play a crucial role in bronchial asthma. As theophylline and procaterol (beta 2-agonist) are used for the treatment of bronchial asthma, the specific functions of eosinophils in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) or platelet activating factor (PAF) were examined using theophylline and procaterol alone and in combination. Eosinophil degranulation induced by PAF or GM-CSF was inhibited by theophylline (10(-6) M-10(-3) M and 10(-6) M to 10(-3) M, respectively) and procaterol (10(-7) M-10(-5) M and 10(-7) M-10(-5) M, respectively). The combination of 10(-4) M theophylline and various concentrations of procaterol provided higher inhibition than 10(-4) M theophylline or procaterol (10(-7) M-10(-5) M). CD11b, which is a triggering molecule for human eosinophil degranulation, showed a significantly inhibited expression of PAF stimulation with 10(-4) M theophylline. CD11b and another triggering molecule for eosinophil degranulation, CD18, showed a significantly inhibited expression of PAF stimulation using a combination of 10(-4) M theophylline and various concentrations of procaterol (10(-5) M-10(-7) M) compared with the inhibition of 10(-4) M theophylline or procaterol (10(-5) M-10(-7) M), but GM-CSF-stimulated eosinophils were not inhibited. Taken collectively, theophylline and/or procaterol have anti-inflammatory effects.

Asthma↗
PubMed1997

Eighteen cases exposed to sarin in Matsumoto, Japan.

Forty-six patients who were exposed to sarin consulted our hospital because of darkness of vision, and ocular pain, vomiting, dyspnea and headaches on June 27 and 28, 1994. Eighteen patients were admitted and 4 of them were in the critical state. There were 6 features: 1) depression of plasma cholinesterase activity (17 of 18 patients, 94%), 2) hypokalemia (4/18, 22%), 3) depression of triglyceride (12/18, 67%), 4) hypocapnia (5/17, 29%), 5) partial pressure of oxygen (PaO2) <80 mmHg, or requirement of O2 inhalation (15/18, 83%), 6) white blood cells (WBC) >9,000 per mm3 (13/18, 72%). Seventeen patients were discharged from hospital, but one patient is still suffering from akinetic mutism after two years.

Adult↗
PubMed1997

Chronic cold exposure stimulates microvascular remodeling preferentially in oxidative muscles in rats.

The effects of 4-week cold exposure on capillary geometry, particularly in terms of the distribution of arteriolar and venular capillaries and their capillary domain areas, were studied for different types of skeletal muscles in male Wistar rats. Morphological data for capillaries and muscles were obtained from muscle cross-sections exposed to a double-staining method that distinguishes arteriolar portions from venular portions of capillaries. In soleus (SOL; type I fibers) and the deep portion of gastrocnemius (GASd; type I and IIa fibers) muscles, total capillary density and density of arteriolar capillary were significantly greater in cold-acclimated (CA) rats than in warm control (WC) rats (p < 0.05). In the superficial portion of the gastrocnemius (GASs; type IIb fibers), however, these changes in capillarity were not observed. After cold acclimation, fiber cross-sectional area was significantly decreased by 21, 28 and 15% in SOL, GASd and GASs (p < 0.05), respectively. In SOL and GASd but not in GASs, capillary domain areas of arteriolar, intermediate and venular portions in CA were significantly smaller than those of the respective portions in WC (p < 0.05). Succinate dehydrogenase activity was significantly increased after cold acclimation, by 31% in SOL and 21% in GASd (p < 0.05). In GASs, however, the activity remained unchanged after cold acclimation. These results suggest that adaptive changes in the oxygen transport system were observed after cold acclimation in the skeletal muscles that are mainly composed of oxidative fibers. These adaptive changes may improve the effective oxygen supply to muscle tissues that contribute to thermogenesis in a cold atmosphere.

Acclimatization↗
PubMed1997

[A case of paraneoplastic retinopathy with serum antibody against retinal soluble 70 kDa protein].

We report a case of paraneoplastic retinopathy in a patient who was found to have small cell carcinoma of the lung and was shown to have serum antibody against retinal soluble 70 kDa protein. A 71-year-old woman visited her ophthalmologist for gradual visual loss in both eyes. Although she underwent uncomplicated cataract surgery in her left eye, she was referred to our hospital because of progressive visual deterioration in November 1994. On admission, her corrected visual acuity was 0.3 OD and hand motion OS. Funduscopic examination showed narrowing retinal arteries, pigment epithelial mottling in the posterior retina bilaterally, and optic disc pallor in the left eye. An electroretinogram demonstrated marked reduction in the a and b waves. Bilateral central scotomas were detected by kinetic perimetry. We pursued further examination for systemic disease, and identified increased serum level of neuron specific enolase and radiographically abnormal shadow in the chest. Transcutaneous needle biopsy of the mediastinum confirmed small cell carcinoma. In western blot analysis the patient's serum reacted strongly with soluble retinal proteins of 70 kDa molecular weight, although the 26 kDa CAR antigen was not labeled. This patient was diagnosed as having paraneoplastic retinopathy due to small cell carcinoma and unusual serum protein which responded to an antigen with a molecular weight of 70 kilodaltons.

Aged↗
PubMed1997

[Cancer-associated retinopathy].

A variety of paraneoplastic syndromes affect the central nervous system including eye. So far, two types of retinopathy are known to be associated with patients with malignancies, cancer-associated retinopathy (CAR), and melanoma-associated retinopathy (MAR). CAR is associated with epithelial cancers, mostly lung small cell carcinoma, and is characterized by retinitis pigmentosa-like retinal degeneration. Usually CAR can be found before an underlying primary cancer is diagnosed. MAR is associated with cutaneous malignant melanoma and is characterized by the relatively sudden onset of photophobia and nyctalopsia. The flash electroretinogram (ERG) of MAR patients shows a negative waveform, reduced b-wave amplitude, and reservation of a-wave amplitude, suggesting that bipolar cells may be affected. CAR and MAR are believed to result from an autoimmune response. In CAR, a calcium binding protein called recoverin, a 70 kDa protein, and neurofilaments are the retinal antigens recognized by the patient's serum. In contrast, the retinal antigens in MAR have not yet been identified, although patient sera specifically recognized retinal bipolar cells in immunocytochemistry.

Animals↗
PubMed1997

[Comparison of retinal breaks between patients with atopic dermatitis and mentally retarded patients with self-inflicted ocular injury].

We compared the distribution of retinal breaks in retinal detachment between patients with atopic dermatitis (AD) and mentally retarded patients who had self-inflicted ocular injury (MR). The cases of AD were 16 eyes in 14 patients (six males and eight females, ranging in age from 15 to 52 years, mean 24.5) and the cases of MR were 6 eyes in 5 patients (5 males, ranging in age from 14 to 25 years, mean 20.2). There was no corneoscleral laceration in either group. In the patients with AD, 14 (87.5%) of 16 eyes had retinal breaks at the vitreous base, and 21 (87.5%) of 24 retinal breaks in 16 eyes were at the vitreous base. In the patients with MR, five (83.3%) of 6 eyes had retinal breaks at the vitreous base and 6(66.7%) of 9 retinal breaks in 6 eyes were at the vitreous base. In both groups, ciliary epithelial breaks and peripheral retinal tears were frequently observed, suggesting that retinal detachment in AD has a pathophysiology similar to traumatic retinal detachment with repeated ocular contusion (self-inflicted injury).

Adolescent↗
PubMed1997

[A study of gastroesophageal reflux by 24-hour esophageal pH monitoring in patients with bronchial asthma].

To evaluate the incidence of abnormal gastroesophageal reflux in patients with bronchial asthma and the influence of drug therapy on the gastroesophageal reflux, we investigated the gastroesophageal reflux patterns using an ambulatory 24-hour esophageal monitoring in 25 healthy volunteers and 58 asthmatics. All the patients were stable conditions at the time of the study. Bronchodilator therapy was continued, if necessary along with steroid inhalation and xanthines. Compared with healthy volunteers, the asthmatics had significantly greater esophageal acid exposure time, more frequent reflux episode, and longer single reflux time. About 70% of asthmatics had abnormal gastroesophageal reflux. Asthma medications were not associated with the incidence of abnormal gastroesophageal reflux. However, asthmatics receiving beta(2)-stimulants therapy (n = 27) had significantly greater esophageal reflux exposure time than those not receiving (n = 31). Our study suggested that most asthmatics have abnormal gastroesophageal reflux unrelated to asthma attack or asthma medications and that beta(2)-stimulants used in asthmatics may worsen gastroesophageal reflux.

Adult↗
PubMed1997

Effect of oxidized low density lipoprotein on thrombomodulin expression by THP-1 cells.

We have investigated the effects of oxidized low density lipoproteins (oxidized LDL) on the expression of TM by THP-1 monocytic cells. TM antigen levels and its cofactor activity for thrombin-dependent protein C activation were increased by oxidized LDL and accompanied by an increase in TM mRNA levels. Incubation of THP-1 cells with 300 microg/ml oxidized LDL for 24 h resulted in an 80% increase of cellular TM antigen levels. Native LDL and acetylated LDL did not affect the TM expression by these cells. The resultant aqueous phase after extraction of oxidized LDL by chloroform/methanol increased the TM antigen levels as well as oxidized LDL. Phorbol 12-myristate 13-acetate (PMA) also increased the TM antigen level 2.1 times the control and was accompanied by the adhesion of cells to plastic dishes and increasing macrophage cell surface antigen CD14 levels. In contrast, oxidized LDL did not induce differentiation to the macrophage. The present results indicate that oxidized LDL increases cellular TM antigen without cellular differentiation and that up-regulation of TM by oxidized LDL in monocytes may have some implication in atherosclerosis.

Arteriosclerosis↗
PubMed1997

[Usefulness of magnetic resonance imaging for managing patients with prosthetic carbon valve in the mitral position].

The safety, findings and clinical usefulness of magnetic resonance (MR) imaging were assessed in patients with a prosthetic carbon valve in the mitral position. In vitro deflection, heating and image distortion due to the magnetic field of a 1.5 tesla MR machine were examined in three carbon valves (CarboMedics, St. Jude Medical and Björk-Shiley valves). In vivo MR imaging of the left ventricular horizontal long-axis, vertical long-axis and short-axis views was performed by electrocardiographically synchronized spin echo and field (gradient) echo techniques in eight patients with prosthetic mitral carbon valves, consisting of six CarboMedics valves, one St. Jude Medical valve and one Björk-Shiley valve. No deflection and significant heating was seen in all three valves in vitro. Although little image distortion was shown in the CarboMedics and St. Jude Medical valves, a small distortion toward the frequency encoded direction was seen in the Björk-Shiley valve but caused no difficulty in assessing the surrounding images. Four of the eight patients had normal sinus rhythm and the other four had atrial fibrillation. The prosthetic valves were depicted as signal voids in the images taken by both spin echo and field echo techniques in vivo. Clear structural information with little image distortion of the adjacent tissues of the prosthetic valves were obtained in all patients, although the image of the Björk-Shiley valve which contained stainless steel in the frame had a slightly stronger distortion than those of the CarboMedics and St. Jude Medical valves which contained titanium. The stainless wire suture material used to close the sternal incision was depicted as a signal void, and the areas of the signal loss were larger in the images taken by the field echo technique than those by the spin echo technique. The images taken by the spin echo technique in patients with atrial fibrillation had reduced quality due to the irregularity of repetition time. Cine MR imaging by the field echo technique showed physiological mitral regurgitant jets as signal loss within the flowing blood, which appeared as high signal intensity, bidirectionally in the bileaflet mechanical valve and unidirectionally in the monoleaflet mechanical valve. An abnormal cavity was seen behind the basal left ventricular myocardium in one patient with a CarboMedics valve. The wall of the abnormal cavity was disrupted abruptly and the rest of the wall consisted of pericardium and adjacent tissue in the image taken by the spin echo technique. The image taken by the field echo technique showed an abnormal jet flow from the basal part of the left ventricular cavity into the abnormal cavity, which was compatible with left ventricular pseudoaneurysm. Two-dimensional echocardiography and Doppler color flow mapping disclosed the abnormal cavity and the abnormal flow inside, but failed to show the connection between the left ventricle and the cavity due to reverberation of the ultrasound signal by the prosthetic valve. These findings suggest that MR imaging is a safe and promising method to assess the complications and valvular function in patients with a prosthetic carbon valve in the mitral position.

Aged↗
PubMed1997

Inhibition of accelerated coronary atherosclerosis with short-term blockade of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in a heterotopic murine model of heart transplantation.

BACKGROUND: Graft arteriopathy limits the long-term survival of allograft recipients. Cardiac allografts in mice develop graft coronary arteriopathy similar to that observed in clinical chronic rejection in human beings. We found that antiintercellular adhesion molecule-1 (ICAM-1) and antilymphocyte function-associated antigen-1 (LFA-1) monoclonal antibodies (mAbs) induce immunologic tolerance to mice with cardiac allografts. METHODS: To evaluate the effects of short-term administration of anti-ICAM-1 plus anti-LFA-1 mAbs in preventing graft arteriopathy, we treated C3H/He mice that received cardiac allografts from BALB/c mice with anti-ICAM-1 plus anti-LFA-1 mAbs for the first 5 days after transplantation. For control studies, FK506 was administered daily to other allograft recipients. Allografts were harvested on day 60. Immunohistochemical analysis was used to detect the expression of ICAM-1 and vascular cell adhesion molecule (VCAM)-1, and in situ reverse transcriptase polymerase chain reaction was performed to detect platelet-derived growth factor (PDGF)-B mRNA expression in the graft arteries. RESULTS: Allografts from mice that received FK506 treatment daily showed significant neointimal thickening with increased expression of ICAM-1, VCAM-1, and PDGF-B mRNA, whereas there was almost no intimal thickening and ICAM-1, VCAM-1, and PDGF-B mRNA expression in the mice that received anti-ICAM-1 plus anti-LFA-1 mAbs. CONCLUSION: Short-term blockade of ICAM-1 and LFA-1 adhesion not only induces immunologic tolerance to cardiac allografts but also prevents graft arteriopathy.

Animals↗
PubMed1997

Assessment of tolerance induction to cardiac allograft by anti-ICAM-1 and anti-LFA-1 monoclonal antibodies.

BACKGROUND: Transplantation tolerance is induced by selective manipulation of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) molecules in the adult mouse. However, the mechanism of this tolerance induction has not been elucidated. METHODS AND RESULTS: C3H/He mice were heterotopically transplanted with BALB/c hearts; recipients were injected with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies (mAbs). Of 3-day administration of both mAbs at 50 micrograms/day, all recipients accepted cardiac allografts indefinitely (n = 20); this also occurred in 5 of 10 mice that were not treated until day +4 or day +5. Long-term cardiac allograft acceptance was also achieved in thymectomized recipients. This tolerance could not be abrogated by the injection of either naive recipient lymphocytes or sensitized lymphocytes taken from the recipient strain mice that rejected the same donor strain hearts. Mixed lymphocyte culture showed that splenocytes from allograft recipient mice treated with the mAbs showed normal allogeneic response without donor alloantigen specificity. CONCLUSIONS: These results demonstrate the unique character of the peripheral tolerance induced by anti-ICAM-1 and anti-LFA-1 mAbs. Further studies are required to elucidate detailed mechanisms of transplantation tolerance development.

Animals↗
PubMed1996

Nonmuscle and smooth muscle myosin heavy chain expression in rejected cardiac allografts. A study in rat and monkey models.

BACKGROUND: Diagnosis of acute rejection and graft arteriosclerosis (chronic rejection) is critical to the success of cardiac transplantation, but accurate diagnosis is often difficult. We have reported that there are three types of vascular myosin heavy chain (MHC) isoforms: SM1, SM2, and SMemb. SM2 is specifically expressed in differentiated smooth muscle cells (SMCs). SMemb is a nonmuscle-type MHC abundantly expressed in SMCs of fetal aorta. METHODS AND RESULTS: To evaluate the usefulness of MHC expression for diagnosis and analysis of acute and chronic rejection, heterotopic cardiac transplantation was performed in rats and monkeys. Immunohistochemistry, electron microscopy, and Northern blot assay were performed to evaluate MHC expression. SMemb was expressed in spindle-shaped cells located in acutely rejected myocardium in the rats and monkeys. These cells were also observed in areas lacking cellular infiltration. These SMemb-positive cells were activated fibroblasts or myofibroblasts. SMemb mRNA was enhanced parallel to the progression of acute rejection. In the coronary arteries of chronically rejected allografts, enhanced SMemb and reduced SM2 expression was observed in both thickened intima and media. The reduced medial SM2 expression was observed before the intimal thickening occurred. These cells were phenotypically modulated SMCs. CONCLUSIONS: Altered expression of MHC isoforms is a sensitive indicator in the diagnosis of acute and chronic cardiac rejection. The pathophysiology of this alteration in MHC isoform expression should be studied further to elucidate the pathogenesis of cardiac rejection.

Animals↗
PubMed1996

Acceptance of primary skin graft after treatment with anti-intercellular adhesion molecule-1 and anti-leukocyte function-associated antigen-1 monoclonal antibodies in mice.

Although a short-term blockade of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) adhesion allows induction of specific tolerance to solid organs, their effect on primary skin allografts is not yet known. Effects of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies (mAb) on primary skin allograft survival were investigated. Recipient mice were treated with either a combination of anti-ICAM-1 and anti-LFA-1 mAbs or a control mAb for the first 22 days. The survival of BALB/c skin in the C3H/He recipient was not prolonged. Subsequently, MHC class I (bm1)- or class II (bm12)-disparate skin grafts were transplanted into C57BL/6 mice. Remarkable prolongation was observed in these combinations. Four of 10 bm12 grafts and 4 of 9 bm1 grafts were accepted for more than 120 days. These results suggest that mouse strain combination is an important factor for skin graft acceptance. We suggest that unique immunogenicity and a lack of vascularization of skin allografts account for the weak immunosuppression produced by anti-adhesion molecule mAbs.

Animals↗