Biomedical subjects
Y Yokota
Publications and source records attributed to Y Yokota.
Oligomeric structures required for complement activation of serum mannan-binding proteins.
Serum mannan-binding protein (S-MBP) comprises a series of homooligomers, and activates complement when it binds to appropriate carbohydrate ligands. In this study, the structural requirements necessary for complement activation were examined for rat, rabbit, and human S-MBPs. On SDS-PAGE under non-reducing conditions, the S-MBPs gave three major bands: large, middle, and small oligomers. Since three subunits (23-25 kDa) form a triple helix (the base structural unit) at the collagen-like domain within the S-MBP molecule, it was estimated that human and rabbit S-MBPs comprise a mixture of pentamers, tetramers, and trimers of the respective structural units. In contrast, rat S-MBP is composed of tetramers, trimers, and dimers. The large and middle oligomers were almost equal in their ability to activate complement, whereas the small oligomers had very low or no activity. Upon digestion with bacterial collagenase, the large and small oligomers were degraded almost completely. In contrast, the middle oligomers remained largely intact, and the surviving middle oligomers retained complete ability to activate complement. The degraded product, trimers of the carbohydrate recognition domain (CRD), did not show any complement activating activity. These data indicate that not only the structural integrity of the S-MBP collagen-like domain and CRD, but also a unique conformational structure present in the middle oligomers are critically important for carbohydrate-mediated complement activation.
Disappearance of neutrophil fluctuations in a child with cyclic neutropenia by combination therapy of granulocyte colony-stimulating factor and high-dose immunoglobulin.
We report on a patient with cyclic neutropenia who was treated by granulocyte colony-stimulating factor (G-CSF) and high-dose immunoglobulin. The serial examination revealed cyclic fluctuations in the numbers of neutrophils, monocytes, platelets in peripheral blood, and in the serum G-CSF concentration. Bone marrow examination confirmed a cyclic fluctuation of both progenitor cells (CFU-GM) and CD10-positive B cells. The therapy of G-CSF followed by high-dose immunoglobulin achieved a disappearance of neutrophil oscillations. It suggested that the combination therapy of G-CSF with high-dose immunoglobulin might be effective for cyclic neutropenia.
Familial aggregation of dilated cardiomyopathy--evaluation of clinical characteristics and prognosis.
To investigate the prevalence, clinical characteristics, and prognosis of familial cases of idiopathic dilated cardiomyopathy (IDC), family screenings were carried out in 117 IDC patients and their relatives. Familial occurrence was suspected in 29 families (25%). Ten families (9%) with 24 patients were confirmed to be familial, but the other 19 families (16%) remained suspected. The age at the time of diagnosis was lower and the cardiac symptoms tended to be milder in the familial group than in the non-familial group, but there were no differences in other clinical parameters. There was also no difference in the survival rate. However, when only NYHA class III and IV patients were selected, the 1-year and 5-year survival rates were lower in the familial group than in the non-familial group. Congestive heart failure was the most common cause of death in the non-familial group, while sudden death was the most common cause of death in the familial group. Among familial IDC patients who were deceased, the left ventricular end-diastolic pressure was higher and the cardiac index was lower at the time of diagnosis than those in patients who were still alive. We conclude that, since the prognosis of familial IDC patients is poor once their cardiac symptoms become severe, early diagnosis and treatment are extremely important.
Characterization of a wild poliovirus type 3 isolated Japan in 1993.
A wild poliovirus type 3 was isolated from a throat swab of a patient with upper respiratory symptoms without paralysis in Shiga Prefecture, in 1993. Wild poliovirus has never been isolated in these nine years in Japan. The most recent isolation of wild poliovirus was of type 1 in 1984 from a case of encephalomyelitis in Aichi Prefecture. Antigenic and PCR-restriction fragment length polymorphism analyses revealed that the Shiga strain was non-Sabin origin. Sequence analysis of the VP1 region confirmed that the isolate was a wild poliovirus type 3. Furthermore, this isolate had higher homology to the isolates from North Vietnam than those from Pakistan or Finland, suggesting that the Shiga strain was imported from Asian area. This strain was also shown to be neurovilurent in transgenic mice carrying human poliovirus receptor gene.
[Comparison of the long-term results of intra or extracardiac implanted bioprosthetic valves].
The long-term results following intra or extracardiac implanted bioprosthetic valves were compared. Forty-one patients, whose average age at the operation was 43.3 +/- 10.7 (mean +/- SD) year-old, were implanted 33 Hancock and 11 Carpentier-Edwards porcine valves, 35 in mitral, 6 in aortic and 3 in tricuspid position. Twenty-five children, whose average age was 6.0 +/- 3.5 year-old (p < 0.01) at the operation, underwent right ventricular-pulmonary artery conduit repair with 16 Hancock, 7 Carpentier-Edwards porcine valves and 2 Ionescu-Shiley pericardial valves. There were only one late death and one operative death in the patients implanted intracardiac bioprosthetic valves. Seven intracardiac and 12 extracardiac implanted bioprosthetic valves were removed at the reoperation for prosthetic valve dysfunction. The probabilities free from reoperation after 7 and 9 years of follow-up was 91% and 82%, respectively, with intracardiac implanted valves, on the other hand 51% (p < 0.05) and 8.6% (p < 0.05), respectively, with extracardiac implanted valves. Valve dysfunction in extracardiac implantation was mainly related to the stenosis due to fusion of comissure and/or calcification. Regurgitation due to tear and/or perforation was mainly associated with intracardiac implanted bioprosthetic valves.
[The influence of electrical time interval indices and aging on the left atrial systolic time intervals].
The influence of aging and heart rate on left ventricular systolic time intervals is well known, but the effects on left atrial systolic time intervals, a new index of left atrial function, remain unknown. The influence of aging and heart rate on left atrial systolic time intervals was investigated in 43 normal subjects (13-72 years of age) by Doppler echocardiography. Atrial pre-ejection period, atrial ejection time, and corrected atrial pre-ejection period were obtained by transmitral Doppler echocardiography. Simple regression analysis showed atrial pre-ejection period significantly correlated with P wave duration (PP; r = 0.78), and PR interval (PR; r = 0.60), but not with RR interval (RR). However, multiple regression analysis showed atrial pre-ejection period significantly correlated only with PP. Simple regression analysis found atrial ejection time significantly correlated with PP (r = 0.38), and PR (r = 0.39), but not with RR. However, multiple regression analysis found atrial ejection time did not correlate with any factor significantly. Aging was significantly correlated with corrected atrial pre-ejection period (r = -0.37), but not with corrected atrial ejection time and atrial pre-ejection period. Atrial ejection time significantly correlated with corrected atrial pre-ejection period (r = -0.37), but not with atrial pre-ejection period. Corrected atrial pre-ejection period is a clinically useful index of left atrial systolic function.
Monozygotic twins of different apparent sex.
We report on twins of unlike sex who shared a 45,X/46,X,+mar karyotype. The mar chromosome was found to be Yq- by DNA analysis. Marker studies, including 8 VNTR loci, yielded a probability of monozygosity of 0.99999996.
Endothelium-derived relaxing factor released by 5-HT: distinct from nitric oxide in basilar arteries of normotensive and hypertensive rats.
1. The role of the endothelium in cerebrovascular responses to 5-hydroxytryptamine (5-HT) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in vitro. 2. Cumulative addition of 5-HT caused concentration-dependent contractions in ring preparations of SHR basilar arteries; the contractile response was smaller in WKY basilar arteries. 3. Removal of the endothelium enhanced markedly the contractile responses to 5-HT in WKY arteries but had only a slight effect in SHR arteries. The responsiveness to 5-HT in WKY arteries after removal of endothelium was comparable to that in SHR arteries. 4. The endothelium-dependent relaxation induced by acetylcholine in WKY basilar arteries was almost abolished by treatment with 10 microM methylene blue or 10 microM NG-nitro-L-arginine (L-NOARG). However, the response to 5-HT was not affected by treatment with methylene blue, L-NOARG or indomethacin. 5. Application of 10-20 mM K+ or 3.2 mM tetraethylammonium (TEA) did not change significantly, or only increased slightly, the resting tension, but markedly enhanced the contractile response to 5-HT in WKY arteries with endothelium. In contrast, the submaximal response to 5-HT in SHR arteries with endothelium was significantly enhanced by 0.3 mM TEA. 6. In the presence of 1 mM TEA, the application of 10 microM L-NOARG further enhanced the responses of 5-HT in WKY arteries with endothelium. In SHR arteries with endothelium, 10 microM L-NOARG per se enhanced slightly but significantly the responses to 5-HT. 7. These results indicate that 5-HT-induced contraction in basilar arteries is substantially attenuated by an endothelium-dependent mechanism in WKY, but to a much lesser extent in SHR. The major relaxing factor released by 5-HT from endothelium in WKY is distinct from NO and may exert its effect by activating K+ channels.
Left atrial backward ejection in symptomatic hypertrophic cardiomyopathy--assessment by transthoracic and transesophageal Doppler echocardiography.
BACKGROUND: During atrial contraction, the left atrium produces both forward ejection to the left ventricle and backward ejection to pulmonary veins. PURPOSE: To determine quantitatively left atrial ejection performance in symptomatic hypertrophic cardiomyopathy (HCM) patients by using left atrial systolic time intervals. METHOD: Thirty-one patients with symptomatic HCM and sinus rhythm and 31 normal subjects were studied with transthoracic and transesophageal Doppler echocardiography. Left atrial pre-ejection period (APEP), corrected atrial pre-ejection period (APEPc), and the duration (AET) and the time velocity integral (IA) of the atrial contraction wave in transmitral flow were determined. The duration (PV-AET) and the time velocity integral (PV-IA) of reverse pulmonary venous flow during atrial contraction were also determined. RESULTS: For normal subjects, significant correlations were found between APEP and electrocardiographic P wave duration (r = 0.78, p < 0.001), and between APEPc and left atrial forward ejection indices (AET: r = -0.42, p = 0.01, IA: r = -0.54, p < 0.05, respectively), but not between APEP and either of the two latter indices. These findings indicate that, for normal subjects, APEPc is a better index of left atrial systolic function than APEP. In contrast, for HCM patients, significant correlations were found between APEPc and left atrial backward ejection indices (PV-AET: r = -0.49; p < 0.005, PV-IA: r = -0.66; p < 0.001, respectively), but not between APEPc and left atrial forward ejection indices. CONCLUSION: Augmentation of left atrial afterload may result in decreased left atrial forward ejection and increased left atrial backward ejection. Thus, both left atrial forward ejection and left atrial backward ejection must be considered in the assessment of left atrial ejection performance in patients with symptomatic HCM.
Binding epitopes for peptide and non-peptide ligands on the NK1 (substance P) receptor.
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Two nonpeptide tachykinin antagonists act through epitopes on corresponding segments of the NK1 and NK2 receptors.
The molecular mechanism of action for two chemically distinct and highly selective, nonpeptide antagonists, CP-96,345 and SR-48,968, was studied by development of a series of chimeric constructs between their respective target receptors, the NK1 (substance P) and NK2 (neurokinin A) receptors. The binding affinities of the natural peptide ligands, substance P and neurokinin A, were not affected by exchanging almost the entire C-terminal half of the NK1 receptor with the corresponding segment of the NK2 receptor. In contrast, it was found that transfer from the NK2 to the NK1 receptor of a segment corresponding to transmembrane segment VI, the amino-terminal half of transmembrane segment VII, and the connecting extracellular loop 3 completely switched the susceptibility for the nonpeptide antagonists. This chimeric exchange, corresponding to 17 nonconserved residues, conveyed full susceptibility for the NK2-specific compound SR-48,968 to the previously unresponsive NK1 receptor--i.e., the Ki value for inhibition of binding of 125I-labeled substance P decreased from > 10,000 to 0.97 nM. At the same time the affinity for the NK1-selective compound CP-96,345 decreased > 30-fold. The actual binding site for SR-48,968 was localized to this region of the NK2 receptor by use of [3H]SR-48,968, which did not bind to the NK1 receptor but bound with similar high affinities to the wild-type NK2 receptor and to the chimeric NK1 receptor with the NK2 receptor segment incorporated around transmembrane segments VI and VII, Kd = 1.5 nM and 1.0 nM, respectively. Our data indicate that two chemically very different nonpeptide antagonists, CP-96,345 and SR-48,968, act through epitopes located around transmembrane segment VI on their respective target receptors and that at least the nonconserved residues in these epitopes are not important for the binding of the natural peptide ligands, substance P and neurokinin A.
[A case of Pulmonary infiltration with eosinophilia syndrome induced by serrapeptase].
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Properties of plasma membrane-induced amylase release from rat parotid secretory granules: effects of Ca2+ and Mg-ATP.
A secretory granular fraction (SG) and a plasma membrane rich fraction (PM) have been isolated from rat parotid gland by differential and Percoll gradient centrifugation. With these two fractions, a cell-free interaction system has been reconstituted to clarify the exocytotic interaction between the secretory granules and plasma membranes, and the conditions of amylase release from SG have been characterized in vitro. The addition of PM into this assay system induced a rapid and transient release of amylase from SG. Some other membranes such as erythrocyte ghosts also mimicked the effect of PM. This release was increased by Ca2+, but was not completely blocked by EGTA. Simultaneous addition of 1 mM ATP with 1 mM MgCl2 (Mg-ATP) in the presence of Ca2+ reduced this release. However, in spite of the existence of Mg-ATP, the stimulation of PM-induced amylase release was caused by Ca2+ in a concentration-dependent manner (10(-7)-10(-3) M). These results suggest that Ca2+ and Mg-ATP should participate as important regulators in the exocytotic interaction between secretory granules and plasma membranes in this system. Furthermore, the differences between our system and intact cells are also discussed.
[Case of von Recklinghausen disease with bullous lung cyst and large cell carcinoma].
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Delineation of structural domains involved in the subtype specificity of tachykinin receptors through chimeric formation of substance P/substance K receptors.
The mammalian tachykinin receptors belong to the family of G protein-coupled receptors and consist of the substance P, substance K and neuromedin K receptors (SPR, SKR and NKR). We constructed 14 chimeric receptors in which seven transmembrane segments were sequentially exchanged between the rat SPR and SKR and examined the subtype specificity of the chimeric receptors by radioligand binding and inositol phosphate measurements after transfection into COS cells. All chimeric receptors showed maximum responses in agonist-induced inositol phosphate stimulation. Detailed analysis of five receptors with agonist selectivity similar to SPR indicated that the selectivity is mainly determined by the region extending from transmembrane segment II to the second extracellular loop together with a minor contribution of the extracellular N-terminal portion. This conclusion was more directly confirmed by an additional chimeric formation in which the introduction of the above middle portion of SPR into the corresponding region of SKR conferred a high affinity binding to substance P. The tachykinin receptors can thus be divided into two functional domains: the region covering transmembrane segments V-VII and responsible for fundamental recognition of the common tachykinin sequence; and its preceding portion involved in evoking subtype specificity by interacting with the divergent sequences of the peptides.
T-independent polyclonal activation of B cells in vitro by immunoglobulin binding substance (IBS) from the granary weevil.
Experiments are described for T-independent polyclonal activation of B cells in vitro by the immunoglobulin binding substance (IBS) from the granary weevil. The affinity-chromatographically purified IBS was used. IBS is a heat-, alkali- and acid-stable glucopeptide which is characterized by non-specific immunoglobulin binding to the Fab fragment. The purified IBS consists of three polymer homologues whose molecular weights are 12-14,000, 25-30,000 and more than 150,000 Da. IBS did not stimulate DNA synthesis by murine T cells, macrophages or plasma cells whereas it did stimulate that by mature B cells without any help from T cells or macrophages. IBS also stimulated both in vitro IgG production by spleen cells and in vitro sensitization of spleen cells by sheep red cells (SRBC). IBS was found to stimulate DNA synthesis by B cells mediated by binding to surface immunoglobulins of B cells. IBS is thought to be a useful amplifier for inducing human hybridomas and a valuable tool for examining mature B cells, both diagnostically and experimentally.
Ontogenic expression of somatostatin-messenger RNA in the intestinal tract of neonatal rats.
Ontogenic expression of somatostatin (SRIF) -messenger RNA (mRNA) in the gastrointestinal tract was examined in neonatal rats aged from 1 day preterm to 60 days postpartum in comparison with that in the hypothalamus. SRIF-mRNA in the hypothalamus was already expressed in prenatal rats and its developmental change was relatively small. In contrast, a unique pattern of SRIF-mRNA expression was seen in the different intestinal regions, gastric antrum, duodenum, jejunum and colon. In the duodenum, SRIF-mRNA level was low at birth, markedly increased during the postnatal 3 days and declined to the previous level by day 21. Jejunal SRIF-mRNA was found in neonates but progressively decreased in a similar way to duodenum. On the contrary, gastric SRIF-mRNA level, which was low during early development, rose rapidly to a peak on day 21 and gradually declined to an adult level. In the colon age-related change was not conspicuous, remaining at a low level. These results indicate that (1) expression of SRIF gene in the intestinal tract is regulated by local factor(s) as well as developmental stage, and (2) shift of SRIF-mRNA pattern occurs during weaning from the duodenum-dominant infantile pattern to the gastric-dominant adult pattern.