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Biomedical subjects

M Isobe

Publications and source records attributed to M Isobe.

At least 181 records · Page 10Linked to original sources
PubMed1997

Heart rate variability in patients with familial amyloid polyneuropathy.

The purpose of this study was to evaluate heart rate variability (HRV) in patients with familial amyloid polyneuropathy (FAP) using the time- and frequency-domain analysis. The study population consisted of 19 patients with FAP, and 19 age and sex matched normal volunteers. The 24-hour Holter recordings of all subjects in sinus rhythm and off medication were analyzed. Five time-domain indices of HRV were computed. The frequency component of HRV was calculated by fast Fourier transform analysis of the RR intervals. The power spectrum of the low frequency (LF) between 0.04-0.15 Hz and high frequency (HF) between 0.15-0.40 Hz and the LF/HF ratio was calculated. Global measures of HRV including the standard deviation of the mean of RR intervals (SDNN) and the standard deviation of 5-minute mean RR intervals (SDANN) were decreased in patients with FAP. Specific vagal influences on HRV including the proportion of RR intervals more than 50 milliseconds different (pNN50) and the HF power on spectral analysis were less in patients with FAP. LF power and LF/HF ratio were more decreased in patients with FAP at the advanced stage than at the early stage. In conclusion, HRV was significantly decreased in patients with FAP at the early stage, and sympathetic activity was more decreased in patients at the advanced stage. These findings suggest that the decrease of the HRV is an indicator of this disease and the power spectral analysis of the HRV is beneficial in assessing the severity of the autonomic dysfunction.

Adult↗
PubMed1997

Recent progress in treating patients with cleft palate.

Over the last 4 decades remarkable progress has been made in the treatment of cleft palate: the rate of attaining normal or nearly normal speech after surgery has risen from about 65% 40 years ago to nearly 90% or more nowadays. One of the main factors is intratracheal intubation anesthesia that has made the surgery much safer and easier. Improved surgical technique and speech therapy also played a great role. This paper deals with two problems: (1) Slight velopharyngeal incompetence: The combined use of fiberscopy and fluorovideoscopy can provide useful information as to: (a) the exact place of the faulty articulation, (b) the detailed pattern of inconsistent velopharyngeal function, (c) changes in articulation induced by speech therapy, and (d) the relation between velopharyngeal function and faulty articulation. All the above information greatly facilitates speech therapy for cleft palate speech. It should be done with utmost care though due to possible adverse effects of radiation. (2) Analysis of faulty articulation. It was revealed that faulty articulations such as laryngeal fricative and affricates, pharyngeal stop, and glottal stop in cleft palate speech, secondary to velopharyngeal incompetence, were produced by articulation in the larynx at various sites such as the epiglottis, arytenoids, aryepiglottic folds and vocal folds. These faulty articulation points were located lower than supposed on the basis of auditory perception.

Adolescent↗
PubMed1997

Application of PCR-RFLP and MASA analyses on 18S ribosomal RNA gene sequence for the identification of three Ginseng drugs.

In order to develop convenient and reproducible methods for the identification of Ginseng drugs at a DNA level, PCR-Restriction fragment length polymorphism (PCR-RFLP) and Mutant allele specific amplification (MASA) analyses were applied, based on differences of the 18S rRNA gene sequence among three Panax species. The PCR product of each species on the 18S rRNA gene was digested with the restriction enzymes Ban II and Dde I. Each fragment gave unique electrophoretic profiles for each species (PCR-RFLP analysis). The extracted DNA of each species was amplified by PCR using a designed species-specific oligonucleotide primer. The expected size of the fragments corresponding to each species were detected only when the optimum temperature and reaction time for annealing and extension were established (MASA analysis). These two analytical methods were carried out on three Ginseng drugs and the same results as in their original plants were obtained. The results suggest that PCR-RFLP and MASA analyses under the established conditions are convenient for identifying three Ginseng drugs. Moreover, to insure completion of the identification, a partial sequence of the plastid gene matK was determined in addition to the 18S rRNA gene. The gene sequences of three Panax species were of 1259 base pairs and that of P. quinquefolius was different from the other two at nucleotide position 102.

Panax↗
PubMed1997

Differences in enzymatic properties of flavin-containing monooxygenase in brain microsomes of rat, mouse, hamster, guinea pig and rabbit.

To characterize flavin-containing monooxygenase (FMO) in brain microsomes of rat, mouse, hamster, guinea pig and rabbit, profiles of its enzyme activities were investigated by HPLC-fluorometrical assay using benzydamine (BZY) as a substrate. The optimum pH of BZY N-oxidation activity in brain microsomes from rat, mouse, hamster or guinea pig was between 8.5 and 9, though that of the rabbit brain microsomes was near 10.0. The activities were thermally unstable in brain microsomes from all the species examined in the absence of NADPH, but the activity in rabbit brain microsomes was rather thermostable in the presence of NADPH. The activity in rabbit brain microsomes was depressed in the presence of 5 mM n-octylamine. In the presence of MnCl2, the enzyme activity in rabbit brain microsomes was markedly decreased. ZnCl2 markedly decreased the enzyme activities in brain microsomes from rat, mouse and rabbit. It was concluded that BZY N-oxidation activity in brain microsomes from rat, mouse, hamster and guinea pig are similar in enzymatic properties but different from the activity of that of rabbit. These results suggest that common FMO isoform(s) other than FMO4 might exist in the brains of the four rodent species tested.

Animals↗
PubMed1997

Synthesis and biological evaluation of novel cyclic enediyne compounds related to dynemicin A as antitumor agents.

Novel cyclic enediyne compounds, which are simple functional analogs of dynemicin A (1) having the bicyclo-[7.3.1]tridec-4-ene-2,6-diyne system, were synthesized and evaluated for the DNA-cleaving ability, in vitro cytotoxicity and in vivo antitumor activity. All of the sulfones 19-24, which were equipped with a 2-(arylsulfonyl)-ethoxycarbonyl group or the 2-(methylsulfonyl)ethoxycarbonyl group as a triggering device, showed both potent DNA-cleaving activity and cytotoxicity against various tumor cell lines. However, these compounds were entirely inactive or only slightly active against murine P388 leukemia in mice. On the other hand, the enediyne 2a having a phenyl carbamate moiety as a stable N-protecting group showed effective antitumor activity both in vitro and in vivo. In particular, it exhibited significant antitumor activity against Lewis lung carcinoma in mice. These results show that the character of the carbamate moiety of the cyclic enediynes strikingly affects their biological activities, that is, the sulfonylethyl carbamate moiety is an effective triggering device for both DNA-cleaving activity and cytotoxicity, and the phenyl carbamate moiety is significant for antitumor activity in vivo. As part of a mechanistic study, the reactivities of 2a and 21 were examined under a weakly basic condition (pH 9.3); both compounds failed to give the Bergman cycloaromatization product.

Alkynes↗
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

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

Subaortic stenosis due to accessory tissue of the mitral valve associated with Ebstein's anomaly in an adult.

A 26-year-old man with a history of effort-induced syncopal attacks was found to have Ebstein's anomaly. A cardiac catheterization revealed a pressure gradient of 77 mmHg between the left ventricle outflow tract which was caused by mitral accessory tissue. The accessory tissue was resected, the aortic valve was replaced, and the Ebstein's anomaly was corrected. The degree of mitral regurgitation was seen to increase following surgery. This is the first reported case of an accessory mitral valve complicated with Ebstein's anomaly.

Adult↗
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↗
PubMed1996

An efficient short-step total synthesis of ganglioside GM3: effective usage of the neighbouring group participation strategy.

We have developed an efficient methodology for highly stereoselective sialylation using 3-position substituted sialic acids and have prepared 2a having a 3 beta-phenylthio group as a sialic donor. Glycosylation of suitably protected lactoside 3 with 2a gave only the alpha-sialyl trisaccharide 16 in good yield. Condensation of the azidosphingosine 4 with the acetate 17 using promotors, DMTST or NIS-TfOH, afforded the glycolipid 18, which was directly transformed to 20 by reduction with Bu3P and subsequent acylation with octadecanoic acid in the presence of WSC. Removal of the protecting groups generated ganglioside GM3 (1).

Carbohydrate Sequence↗
PubMed1996

Bone morphogenetic protein encapsulated with a biodegradable and biocompatible polymer.

To develop a controlled release system for bone morphogenetic protein (BMP), poly(DL-lactide-co-glycolide) (PLGA) capsules containing BMP were prepared by an interfacial precipitation method using a water-in-oil-in-water emulsion. The surface morphology, particle size distribution, and hydrolytic degradation rate of the PLGA capsules were examined. The encapsulation yield and release rate of BMP in vitro were measured using fluorescein isothiocyanate-labeled BMP. The amount of BMP released from PLGA capsules increased between days 3 and 5. In addition, the effectiveness of BMP encapsulated in PLGA to induce bone formation in vivo was also examined by subcutaneous implantation in rats. Complete digestion of the capsules and new bone formation including bone marrow were identified by histologic examination of harvested tissues at 3 weeks after implantation. These results demonstrated that encapsulation of BMP with PLGA could be a promising method to induce bone in clinics.

Animals↗
PubMed1996

Cardiac sarcoidosis: diagnostic, prognostic, and therapeutic considerations.

Cardiac involvement in patients with sarcoidosis is an important consideration for those who are concerned with this strange disease. Sarcoidosis is not an acute malignant disease but may be noticed at the time of sudden, expected death as fatal myocardial sarcoidosis at autopsy. Even with modern advances in our ability to diagnose heart disease, cardiac sarcoidosis is still often overlooked because of its subclinical disease progression. In view of this, an extensive review of previously published literature and of our own case analyses has been carried out because of the authors' long-term experience with performing Konno's endomyocardial biopsy, which was originally developed in 1962 at the author's institution. However, the sensitivity of endomyocardial biopsy in detecting sarcoid granuloma is low (20-30%), and, instead, various kinds of nongranulomatous pathologies are often seen. During the course of our research it was found that there might exist a racial difference in cardiac sarcoidosis. Cardiac death was much more frequent in Japanese patients. The possibility that heart disease in sarcoidosis is caused by cor pulmonale due to advanced pulmonary fibrosis should be reevaluated because only a limited amount of background data is available. The author's review clarified the fact that cardiac sarcoidosis is caused by myocardial or pericardial involvement, resulting in various kinds of bradyarrhythmias or tachyarrhythmias and/or congestive heart failure. Electrocardiographic (ECG) and Holter monitor readings provide a simple and effective method for early detection of this disease. The incidence of ECG abnormalities in a total of 963 sarcoidosis patients was 22.1%, which was more frequent than that of the sex- and age-matched healthy control subjects (17.9%; p < 0.025). Echocardiography and radionuclide studies also provide useful clinical information. Careful follow-up and early corticosteroid administration followed by small maintenance doses may prevent the progression of the disease and improve prognosis. Owing to the progress in antiarrhythmic drugs and pacemaker implantation, the primary cause of death in cardiac sarcoidosis has changed from sudden death (1976 report) to congestive heart failure (1985 report).

Adrenal Cortex Hormones↗