Biomedical subjects
Publications and source records attributed to S Sano.
Fourteen year old female visited our hospital suffering from anterior chest pain. Chest CT revealed anterior mediastinal mass which had multiple cystic lesions, 8.5 x 7.0 x 5.5 cm in size. Tumor extirpation had performed by median sternotomy and pathological diagnosis was mature teratoma. CA 19-9 and CEA in the cystic fluid had elevated 32,790 U/ml and 768 ng/ml, respectively.
Between November 1992 and February 1996, 84 patients (less than 3 months of age) underwent open heart surgery. Among 76 patients except 8 who required mechanical circulatory support, the sternum was left open. The indication of open sternotomy was hypoplastic left heart syndrome in 14 patients and unstable hemodynamics in 4 patients. Three patients died before delayed sternal closure. Delayed sternal closure was carried out in 15 patients with a mean of 4.7 days postoperatively. By the time of sternal closure, blood pressure, left atrial pressure and respiratory parameters improved and inotropics were reduced with the minus fluid balance. One patient died of sepsis 4 days after delayed sternal closure. Delayed sternal closure was effective modality to neonates or early infants after complex open heart surgery.
BIT/SHPS-1/SIRPalpha/P84 is a unique molecule with a high degree of homology with immune antigen recognition molecules (immunoglobulin, T-cell receptor and MHC), and is highly expressed in the brain. The extracellular region contains three immunoglobulin-like domains (V-type, C1-type and C1-type), and the intracellular region contains two signalling motifs that interact with SHP-2 protein tyrosine phosphatase. BIT-coated plates support cell-substrate adhesion and neurite extension of neurons, and BIT participates in neuronal signal transduction. Diversity of the V-type domain sequences of human BIT has been reported. In the present study we analysed the structure of the mouse BIT gene (Bit). The protein coding region consists of eight exons corresponding to a signal peptide, a V-type domain, a C1-type domain, a C1-type domain, a transmembrane region and three parts of one cytoplasmic region. The two signalling motifs are encoded in one exon. Four splicing forms of mouse BIT were revealed. We also found the sequence diversity in three mouse strains, namely BALB/c, 129/Sv and C57BL/6. The substitution patterns of amino acids and nucleotides indicate positive pressure to alter the amino acids in the V-type domain in evolution. Immunoblot analyses showed that mouse BIT and human BITalpha are predominantly expressed in the brain. On the bases of these findings we discuss the possibility that BIT contributes to the genetic individuality and diversity of the brain.
To elucidate the biological role of Stat3 in the skin, conditional gene targeting using the Cre-loxP system was performed as germline Stat3 ablation leads to embryonic lethality. K5-Cre;Stat3(flox/-) transgenic mice, whose epidermal and follicular keratinocytes lack functional Stat3, were viable and the development of epidermis and hair follicles appeared normal. However, hair cycle and wound healing processes were severely compromised. Furthermore, mutant mice expressed sparse hair and developed spontaneously occurring ulcers with age. Growth factor-dependent in vitro migration of Stat3-disrupted keratinocytes was impaired despite normal proliferative responses. We therefore conclude that Stat3 plays a crucial role in transducing a signal required for migration but not for proliferation of keratinocytes, and that Stat3 is essential for skin remodeling, including hair cycle and wound healing.
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We analyzed total Ca handling of the left ventricle (LV) in the mildly failing heart preparation induced by a temporary intracoronary Ca overloading intervention in eight excised and cross-circulated canine hearts. This Ca intervention consisted of interruption of coronary blood perfusion by Ca-free oxygenated Tyrode perfusion for 10 min followed by high-Ca (16mmol/l) oxygenated Tyrode perfusion for 5 min. This intervention decreased the LV contractility index, Emax (end-systolic maximum elastance), by 40% after restoration of the blood cross-circulation. We expected a Ca overload or paradox failing heart resembling the postischemic stunned heart and being characterized by an increased O2 cost of Emax. However, LV O2 consumption under mechanically unloading conditions decreased by 30% from control without increasing the O2 cost of Emax. To obtain a mechanistic view of this failing heart, we investigated cardiac total Ca handling by our integrative analysis method. In this method, we obtained the internal Ca recirculation fraction (RF) from the decay beat constant of the postextrasystolic potentiation following each sporadic spontaneous extrasystole in these failing LVs. We combined the RF with the decreased Emax and the unchanged O2 cost of Emax in our recently developed formula of total Ca handling. We found that these failing LVs had a slightly but significantly increased RF accompanied by either a slightly increased futile Ca cycling or a slightly decreased Ca reactivity of Emax, or both. Any of these three possible changes can account for the unchanged O2 cost of Emax. This result indicates that the present mildly failing heart has not yet fallen into a typical Ca overload or paradox by the temporary Ca overloading intervention.
This study was designed to verify the effect of reperfusion of donor hearts in a perfusion apparatus after 60 min of global ischemia prior to heart transplantation. Thirteen dogs were exsanguinated from the femoral artery and cardiac arrest was achieved. The hearts were left in situ at room temperature (25 degrees C) for 60 min. In group A (n = 7), the hearts were excised and reperfused 60 min after cardiac arrest in the perfusion apparatus with substrate-enriched warm blood cardioplegia (WBCP) containing a hydroxyl radical scavenger, EPC, followed by 45 min of blood perfusion. Next, the hearts were preserved in cold (4 degrees C) University of Wisconsin (UW) solution. In group B (n = 6), the hearts were perfused with cold (4 degrees C) St. Thomas' solution 60 min after cardiac arrest and preserved in cold UW solution. Thereafter, all hearts in both groups were transplanted orthotopically to recipient dogs. In group A, 6 of 7 dogs were weaned from cardiopulmonary bypass (CPB). In group B, only 2 of 6 dogs were weaned from CPB. Moreover, 3 of the 6 hearts in group B did not start beating after transplantation (stone heart). This study suggested reperfusion of the donor heart in the perfusion apparatus with WBCP to be a beneficial preconditioning method when utilizing 60-min arrested hearts for transplantation.
PURPOSE: To measure the dynamic penetration process of lidocaine, lidocaine concentration (Ci) and pH (pHi) in squid giant axon, and to determine the times and Ci of disappearance and reappearance of action potentials (AP). METHODS: Lidocaine solutions adjusted to four different pHs (pH = 5.5, 6.8, 7.8 and 9.0) were externally administered to the axon and Ci and pHi were measured using lidocaine and pH microsensors. The times and Ci when the AP just disappeared and reappeared were recorded. In addition, for comparison with Ci, the lidocaine content in the whole axon (Cw) was measured with high-performance liquid chromatography (HPLC). RESULTS: The Ci (charged plus uncharged) was 1.5 times greater than the uncharged form of administered lidocaine. The changes in pHi depended on the increase in Ci. The AP disappeared only after administration of high pH lidocaine solutions (pH = 7.8, 9.0) and reappeared by washing out the solution in the chamber. Nerve block occurred more rapidly at pH 9.0 than at pH 7.8, and the time after washing out the lidocaine was longer at pH 9.0 than at pH 7.8. The mean Ci and charged lidocaine concentration in the axoplasm, when the AP disappeared or reappeared, were lower at pH 9.0 than at pH 7.8 (P < 0.05). CONCLUSION: Uncharged lidocaine penetrates the axon membrane to the axoplasm where it changes to the charged form and is concentrated in the axon membrane and axoplasm. External application of uncharged lidocaine plays a role in modulating nerve conduction.
The antiarrhythmic effect of magnesium sulfate (Mg) as well as the hemodynamics were studied using the coronary ligation and reperfusion models in rats. In the study on coronary ligation arrhythmia, i.v. administration of Mg (0.6, 2, 6, 20 and 60 micromol) was conducted at 5 min after coronary ligation. Mg had an action to decrease the total number of premature ventricular contraction (PVC), the duration of ventricular tachycardia (VT), the frequency of VT and ventricular fibrillation (Vf) and the mortality ratio for 30 min after coronary ligation. In the 6-60 micromol groups, significant antiarrhythmic action (p < 0.01 vs. control) was attained. In the study on reperfusion arrhythmia, i.v. administration of Mg (20, 60 and 200 micromol) was conducted at 4 min after coronary ligation, and at 1 min after ligation, the coronary artery was reperfused. Mg had an action to decrease the frequency of Vf, the mortality ratio and the duration of VT and Vf and to extend the interval between the initiation of reperfusion and the occurrence of VT and Vf for 10 min after reperfusion. In the 200 micromol group, significant antiarrhythmic action (p < 0.05 vs. control) was attained. Administration of Mg decreased the heart rate and blood pressure. We concluded that Mg can control myocardial ischemia-induced and reperfusion-induced arrhythmia and that sudden cardiac death which occurs as a result of arrhythmia can be prevented.
Mycobacterium paratuberculosis has been suggested as a causative organism of Crohn's disease. Despite a long-term debate to prove this possibility, the role of this bacteria in the pathogenesis of Crohn's disease is still a subject of controversy. In the present study, serum antibodies (IgG, IgA, and IgM) to the protoplasmic antigen of M. paratuberculosis were quantified in patients with Crohn's disease and in control subjects by using an enzyme-linked immunosorbent assay whose specificity was increased by preabsorbing the sera with cell extracts of Mycobacterium phlei. As compared to normal controls (1/20; 0.062+/-0.022), a significant difference was seen in the antibody-positive prevalence rate and mean values of the serum IgG titer in patients with Crohn's disease (5/13; 0.102+/-0.039) (P < 0.05), but not in patients with ulcerative colitis (2/20; 0.065+/-0.035) and tuberculosis (0/4; 0.053+/-0.008). No significant differences were seen in the antibody-positive prevalence rate and mean values of the serum IgA and IgM titers among the four study groups. These results indicate the unique immune response to M. paratuberculosis in patients with Crohn's disease, suggesting that this organism may play some role in the pathogenesis of Crohn's disease.
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Shp2, a protein tyrosine phosphatase possessing SH2 domains, is utilized in the intracellular signaling of various growth factors. Shp2 is highly expressed in the CNS. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, which also shows high levels of expression in the CNS, exerts neurotrophic and neuromodulatory effects in CNS neurons. We examined how BDNF utilizes Shp2 in its signaling pathway in cultured cerebral cortical neurons. We found that BDNF stimulated coprecipitation of several tyrosine-phosphorylated proteins with anti-Shp2 antibody and that Grb2 and phosphatidylinositol 3-kinase (PI3-K) were coprecipitated with anti-Shp2 antibody in response to BDNF. In addition, both anti-Grb2 and anti-PI3-K antibodies coprecipitated Shp2 in response to BDNF. The BDNF-stimulated coprecipitation of the tyrosine-phosphorylated proteins, Grb2, and PI3-K with anti-Shp2 antibody was completely inhibited by K252a, an inhibitor of TrkB receptor tyrosine kinase. This BDNF-stimulated Shp2 signaling was markedly sustained as well as BDNF-induced phosphorylation of TrkB and mitogen-activated protein kinases. In PC12 cells stably expressing TrkB, both BDNF and nerve growth factor stimulated Shp2 signaling similarly to that by BDNF in cultured cortical neurons. These results indicated that Shp2 shows cross-talk with various signaling molecules including Grb2 and PI3-K in BDNF-induced signaling and that Shp2 may be involved in the regulation of various actions of BDNF in CNS neurons.
BIT (brain immunoglobulin-like molecule with tyrosine-based activation motifs) is a membrane glycoprotein that has two cytoplasmic TAMs (tyrosine-based activation motifs). We previously reported that tyrosine-phosphorylated TAMs of BIT interact with the Src homology 2 domain-containing protein tyrosine phosphatase SHP-2 both in vitro and in transfected cells, and this association results in a potent stimulation of the phosphatase activity of SHP-2. Both BIT and SHP-2 are highly expressed in the mammalian brain, and they may play important roles in the regulation of synaptic function. In this study, we found that nerve growth factor (NGF) treatment of PC12 cells leads to the tyrosine phosphorylation of BIT and a subsequent complex formation between BIT and SHP-2. Furthermore, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) also induced the tyrosine phosphorylation of BIT and the association with SHP-2 in primary cultured rat neurons. Our results suggest that the BIT-SHP-2 signaling pathway is a novel signal transduction mechanism of neurons that acts in response to neurotrophic factors such as NGF, BDNF, and NT-3.
OBJECTIVE: To investigate whether autonomic nervous activity is involved in the recurrence of spontaneous coronary spasm in variant angina. DESIGN: Retrospective analysis. SETTING: Cardiology department of a university hospital. PATIENTS: 18 patients with variant angina were divided into single attack group (SA; nine patients) and multiple attack group (MA; nine patients) according to the frequency of ischaemic episodes with ST segment elevation during 24 hour Holter monitoring. METHODS: Heart rate variability indices were calculated using MemCalc method, which is a combination of the maximum entropy method for spectral analysis and the non-linear least squares method for fitting analysis, at 30 second intervals for 30 second periods, from 40 minutes before the attack to 30 minutes after the attack. High frequency (HF; 0.04-0.15 Hz) was defined as a marker of parasympathetic activity, and the ratio of low frequency (LF; 0.15-0.40 Hz) to high frequency (LF/HF) as an indicator of sympathetic activity. The averaged value during the 40 to 30 minute period before an attack was defined as the baseline. RESULTS: Compared with baseline, the HF component decreased in both groups at two minutes before the attack (p < 0.01), and the LF/HF ratio decreased at three minutes before the attack (p < 0.01). The baseline LF/HF was lower in the MA group than in the SA group (p < 0. 01). CONCLUSIONS: A reduction of sympathetic activity may play a key role in determining the recurrence of transient ischaemic events caused by spontaneous coronary spasm in patients with variant angina.
Exercise seldom provokes tachycardia in patients with paroxysmal supraventricular tachycardia (PSVT). This report presents a case of exercise-induced uncommon atrioventricular nodal reentrant tachycardia (AVNRT) with sick sinus syndrome. Treadmill exercise testing provoked AVNRT of long RP' with good reproducibility. Uncommon AVNRT was confirmed by the lack of atrial pre-excitation during PSVT and para-Hisian pacing. The patient has been successfully treated with verapamil and DDD pacing for 5 years.
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To analyze the potential of the active oxygen-scavenging system of chloroplasts, we introduced Escherichia coli catalase into tobacco chloroplasts. Photosynthesis of transgenic plants was tolerant to high irradiance under drought conditions, while the wild plants suffered severe damage in photosynthesis under the same conditions. Irrespective of responses to the stress, ascorbate peroxidase was completely inactivated both in the transgenic and wild-type plants. These findings are contrary to the established idea that the ascorbate peroxidase-mediated antioxidative system protects chloroplasts from oxidative stress.
Culture of Desulfovibrio vulgaris in a medium supplemented with 5-aminolevulinic acid and L-methionine-methyl-d3 resulted in the formation of porphyrins (sirohydrochlorin, coproporphyrin III, and protoporphyrin IX) in which the methyl groups at the C-2 and C-7 positions were deuterated. A previously unknown hexacarboxylic acid was also isolated, and its structure was determined to be 12, 18-didecarboxysirohydrochlorin by mass spectrometry and 1H NMR. These results indicate a primitive pathway of heme biosynthesis in D. vulgaris consisting of the following enzymatic steps: (i) methylation of the C-2 and C-7 positions of uroporphyrinogen III to form precorrin-2 (dihydrosirohydrochlorin); (ii) decarboxylation of acetate groups at the C-12 and C-18 positions of precorrin-2 to form 12,18-didecarboxyprecorrin-2; (iii) elimination of acetate groups of the C-2 and C-7 positions of 12,18-didecarboxyprecorrin-2 to form coproporphyrinogen III; and (iv) conversion of coproporphyrinogen III to protoporphyrin IX via protoporphyrinogen IX. We isolated the following three enzymatic activities involved in steps i-iii from the soluble fraction of the cells by anion-exchange chromatography: S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase, precorrin-2 12,18-acetate decarboxylase, and 12, 18-didecarboxyprecorrin-2 2,7-decarboxymethylase; all enzymic products were converted into autooxidized methyl esters and analyzed by thin-layer chromatography, UV-visible (UV-VIS) absorption, and mass spectrometry. The enzymatic reactions in D. vulgaris shed new light on porphyrin biosynthesis at an early stage in the evolution of prokaryotes.