Polarized XAFS study of the atomic displacements and phase transitions in KNbO3.
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Journal Article↗
Biomedical subjects
K Yanagi
Publications and source records attributed to K Yanagi.
Estrogen deficiency accelerates autoimmune exocrinopathy in murine Sjögren's syndrome through fas-mediated apoptosis.
Estrogenic action has been suggested to be responsible for the strong female preponderance of autoimmune diseases, but the role of estrogens in the female has not been well characterized. We evaluated the effects of estrogen deficiency in a murine model for autoimmune exocrinopathy of Sjögren's syndrome (SS). Severe destructive autoimmune lesions developed in the salivary and lacrimal glands in estrogen-deficient mice, and these lesions were recovered by estrogen administration. We detected an intense estrogen receptor in splenic CD8(+) T cells compared with that in CD4(+) T cells, and concanavalin-A-stimulated blastogenesis of splenic CD8(+) T cells with estrogens was much higher than that of CD4(+) T cells. We found a significant increase in serum autoantibody production against the organ-specific autoantigen alpha-fodrin. Moreover, an increased proportion of TUNEL+ apoptotic epithelial duct cells was observed in estrogen-deficient mice. It was demonstrated that Fas-mediated apoptosis in cultured salivary gland cells was clearly inhibited by estrogens in vitro. These results indicate that dysfunction of regulatory T cells by estrogen deficiency may play a crucial role on acceleration of organ-specific autoimmune lesions, and estrogenic action further influences target epithelial cells through Fas-mediated apoptosis in a murine model for SS.
Animals↗
Development of a packed-bed type bioartificial liver: tissue engineering approach.
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Animals↗
Requirement for splenic CD4+ T cells in the immune privilege of the anterior chamber of the eye.
Injection of antigen into the anterior chamber of the eye induces suppression of antigen-specific DTH, called anterior chamber-associated immune deviation (ACAID). It has been shown that the spleen is required for the induction of ACAID and detecting the ACAID-inducing signal from the eye. To examine the in vivo role of spleen cells, fractions of spleen cells were adoptively transferred into splenectomized mice. The present study showed that DTH was not suppressed in splenectomized mice, but was inhibited in splenectomized mice transferred with a primed CD4+ T cell-containing fraction of spleen cells. This indicates that the splenic CD4+ T cells comprise the regulatory T cells for the DTH response. When we examined the cytokine profile of the infiltrating T cells in the eye of primed mice by reverse transcriptase-polymerase chain reaction (RT-PCR), we found that they expressed IL-4, IL-10 mRNA (Th2 type), but not IL-2 and interferon-gamma (IFN-gamma) mRNA (Th1 type). By contrast, T cells which can elicit normal DTH response expressed IL-2 and IFN-gamma mRNA. These results suggest that splenic CD4+ T cells comprising the regulatory phenotype are required for the induction of ACAID, and that a DTH response to the antigen may be prevented by Th2-dominant CD4+ T cells.
Animals↗
[New operative technique to resect of peripheral bronchogenic carcinoma with chest wall invasion using Kent's retractor].
We report the new operative technique for resection of peripheral bronchogenic carcinoma with chest wall invasion using Kent's retractor and hook suspender. Standard muscle sparing thoracotomy cannot obtain the adequate operative field in the posterior chest wall under the scapula because of sparing the latissimus dorsi muscle. To obtain a sufficient operative field at the operation for en bloc chest wall resection, especially with the area of the posterior chest wall under the scapula, resection of the trapezius muscle, rhomboideus major muscle, and latissimus dorsi muscle has been added to muscle-sparing thoracotomy. Through our new technique using Kent's retractor and hook suspender that has been used in the abdominal surgery, assistant surgeon can be eliminated in favor of hanging up the scapula, which is able to be performed much easier to obtain a good operative field. To use the Kent's retractor and hook suspender, the scapula is lifted upward and cranially. With these procedures, the proximal portion of the first, second and third ribs in the posterior chest wall covering by the scapula is able to resect from vertebrocostal junction with muscle-sparing thoracotomy. We examined the apparatus for a case of the right upper lung carcinoma with invasion to the posterior chest wall. We performed right upper lobectomy with chest wall in the area of the second, third and forth ribs with suspending the scapula by Kent's retractor after muscle-sparing thoracotomy.
Adenocarcinoma↗
[A case of traumatic aneurysm of innominate artery with occlusion of right subclavian artery].
A 42-year-old woman with history of chest blunt trauma from an automobile accident 250 days earlier had suffered easy fatigability of the right upper extremity. She had difference of blood pressure between upper extremities, 94/60 mmHg in the right and 126/70 mmHg in the left. Chest CT showed dilation of the innominate artery which compressed the trachea. Aortography showed an aneurysm of the innominate artery and occlusion of the right subclavian artery at its origin. The aneurysm of the innominate artery was resected and replaced with a 6 mm Dacron graft with aid of the external shunt. The right subclavian artery was also reconstructed with same graft. The aneurysm of the innominate artery should be suspected as a rare complication in blunt trauma of the chest.
Adult↗
Localization of GABA receptor rho 2 and rho 3 subunits in rat brain and functional expression of homooligomeric rho 3 receptors and heterooligomeric rho 2 rho 3 receptors.
Ionotropic GABA receptors that are composed of rho subunits act to gate bicuculline-insensitive Cl- currents. Reverse transcription-polymerase chain reaction analysis revealed that the expression of rho 2 mRNA in adult rat brain was approximately eight times higher than mRNA in the rat brain at embryonic day 16, while that of rho 3 in the embryonic brain was approximately six times higher than in the adult brain. In the adult rat brain the rho 3 mRNA was present in the mesencephalon, hippocampus, cerebellum, thalamus and basal ganglia. In situ hybridization has been used to demonstrate the presence of rho 2 mRNA in the hippocampal CA1 region of the 8-day-old rat, and in the CAl region of the hippocampus, lateral geniculate nucleus, superficial gray layer of the superior colliculus and the pars compacta of the substantia nigra of the adult rat. When the homooligomeric rho 3 receptors were expressed in Xenopus oocytes, applications of agonists induced ionic currents. The order of potency of the agonists was muscimol > GABA = trans-4-amino-crotonic acid > cis-4-aminocrotonic acid. The ionic currents induced by GABA were blocked by picrotoxinin and Zn2+ in dose-dependent manner. In heterooligomeric rho 2 rho 3 receptors, picrotoxinin sensitivity was significantly reduced.
Amino Acid Sequence↗
Anti-120-kDa alpha-fodrin immune response with Th1-cytokine profile in the NOD mouse model of Sjögren's syndrome.
Our recent study suggested that the 120-kDa alpha-fodrin molecule may be an important autoantigen in the pathogenesis of Sjögren's syndrome, and anti-120-kDa alpha-fodrin antibodies have been detected in patients with Sjögren's syndrome. Here we have analyzed anti-120-kDa alpha-fodrin immune responses during development of spontaneous autoimmune sialadenitis in NOD mice as a model of Sjögren's syndrome. We found specific autoantibody production against 120-kDa alpha-fodrin, and its production correlated closely with autoimmune sialadenitis. A specific T cell response of splenocytes against the 120-kDa alpha-fodrin autoantigen was observed in NOD mice from the early onset of autoimmune sialadenitis. In addition, production in vitro by splenic T cells of cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), but not IL-4, was detected by enzyme-linked immunosorbent assays. We found up-regulation of local cytokine genes, including those of Th1 type (IL-1beta, TNF-alpha, IL-2, IFN-gamma, IL-6), as well as IL-10 and IL-12(p40), in the tissue-infiltrating cells during the course of autoimmune sialadenitis. These findings suggest that in spontaneous autoimmune sialadenitis in NOD mice, there may be a specific anti-120-kDa alpha-fodrin immune response in the development of autoimmune lesions resembling human Sjögren's syndrome, and that the autoreactive Th1 cells possess an up-regulated cytokine profile besides IL-10 and IL-12.
Amino Acid Sequence↗
Actions of cyclic esters, S-esters, and amides of phenyl- and phenylthiophosphonic acids on mammalian and insect GABA-gated chloride channels.
Cyclic esters, S-esters, and amides of phenyl(thio)phosphonic acid were synthesized to probe the interaction between noncompetitive antagonists of ionotropic gamma-aminobutyric acid (GABA) receptors and their binding site. Some of these compounds competitively inhibited the specific binding of [3H]EBOB, a noncompetitive GABA antagonist, to rat-brain and housefly-head membranes. The trans isomer of the ester bearing a tert-butyl group at the 5-position and a bromine atom at the p-position (5t) was most potent in rat receptors with an IC50 value of 40 nM, while the trans isomer of the S-ester bearing the same substituents (10t) was most potent in housefly receptors with an IC50 value of 55 nM. In both cases, the corresponding amide analogue (12t) was less potent. The potencies of 5t and 12t tended to decrease in the presence of GABA, particularly in housefly receptors, while that of 10t remained unchanged. The rank order of activity in inhibiting [3H]EBOB binding to housefly-head membranes in the presence of GABA (10t > 5t > 12t) was in accord with that of insecticidal activity. S-Ester 10t depressed 10 microM and 300 microM GABA-induced 36Cl- influx into mouse cerebral synaptoneurosomes, whereas ester 5t depressed 10 microM GABA-induced 36Cl- influx but not 300 microM GABA-induced flux. Amide 12t was inactive at both GABA concentrations. These findings indicate that six-membered cyclic phenylthiophosphonic acid derivatives act as noncompetitive antagonists of GABA receptors and suggest that 10t is able to bind to the receptor in the open, desensitized, and closed states, whereas the affinity of 5t and 12t is lower in the open and desensitized states than in the closed state. The derivatives have similar structures except for the heteroatoms at the 1- and 3-positions, so that the heteroatoms may play a unique role when antagonists bring the open state of the GABA-gated channel to the desensitized or closed state.
Affinity Labels↗
Identification of Streptococcus mutans PAc peptide motif binding with human MHC class II molecules (DRB1*0802, *1101, *1401 and *1405).
A surface protein antigen (PAc) of Streptococcus mutans, in particular the A-region of this PAc molecule, has been noted as a possible target in research for an effective dental caries vaccine. To identify the antigenic peptide binding to major histocompatibility complex (MHC) class II (HLA-DR) molecules in the A-region, we prepared a panel of overlapping synthetic peptides in the second unit of the A-region, and established that a simple enzyme-linked immunosorbent assay (ELISA) binding assay could be achieved by incubating the DR-crude. Binding to DR molecules of these peptides from nine donors was investigated by using the ELISA binding assay. It was revealed that the PAc(316-334) peptide bound more strongly to the HLA-DR molecule in seven out of nine subjects. In particular, DR8 (DRB1*0802), DR5 (DRB1*1101) and DR6 (DRB1*1402 and *1405), which bound strongly to PAc(316-334) peptide, were identified. Moreover, we synthesized glycine-substituted peptide analogues of the peptide and examined the binding motif of the binding region. As a result, the multiple binding motif in DR8, DR5 and DR6 was found in L-RV-K-A. It is suggested that a peptide vaccine for dental caries that is more effective for humans, with fewer adverse side-effects, could be designed by combining the multiple binding motif with the B-cell epitope to produce only the inhibiting antibody against dental caries. The peptide could therefore be useful for peptide vaccine development in the general human population.
Adult↗
Neonatal lupus erythematosus: maternal IgG antibodies bind to a recombinant NH2-terminal fusion protein encoded by human alpha-fodrin cDNA.
IgG antibodies to a cleavage product of alpha-fodrin (120 kDa alpha-fodrin) have recently been identified as organ-specific autoantibodies in primary Sjögren's syndrome. In this study, we examined seroreactivity of mothers and infants with neonatal lupus erythematosus (NLE) to a recombinant NH2-terminal protein (120 kDa alpha-fodrin) of human alpha-fodrin. Serum samples were collected during the perinatal period in seven pregnancies of five mothers delivering offspring with NLE. Anti-120 kDa alpha-fodrin antibodies were identified by immunoblotting in six of seven perinatal maternal sera of offspring with NLE: one of two congenital heart block offspring and all five offspring with cutaneous NLE. These antibodies were placentally transmitted to infants. One of the five mothers had primary Sjögren's syndrome, and four were asymptomatic. One asymptomatic mother did not demonstrate anti-120 kDa alpha-fodrin activity at the time of the first delivery of a congenital heart block infant, but was found to be positive at the time of subsequent delivery of a second child with cutaneous NLE. We propose that maternal antibodies to 120 kDa alpha-fodrin may be an additional serologic marker for the risk of NLE in anti-Ro/SS-A positive women.
Autoantibodies↗
[Removal of bile duct stones by endoscopic papillary balloon dilatation (EPBD) of papilla of Vater].
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Adult↗
[Guideline for macrolide treatment of chronic paranasal sinusitis (draft)].
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Adult↗
[Dorsal sympathectomy for palmar hyperhidrosis by the thin thoracoscope].
The purpose of this study was to examine the efficiency to use by the thin thoracoscope for the palmar hyperhidrosis. General anesthesia with double lumen endotracheal intubation was used in all cases. A 2 mm incision made in the anterior axillary line in the third intercostal space. Pneumothorax was obtained by insufflation 1.5-2 L of CO2. A 2 mm endoscopic trocar was inserted through this incision, and a 2 mm, 0-degree scope (Autosuture, USA) was introduced. A second 2 mm trocar was inserted in the middle axillary line in the fourth intercostal space, through which a straight endoscopic seizer was introduced. The chain was dissected by electrocutting the white and gray rami and was incised over the second and third ribs. To avoid puemothorax, 8 F thoracic catheter was introduced through a guide wire which was inserted through a 2 mm trocar. The lung was expanded, and then the thoracic catheter was removed. We performed six sympathectomies on three female patients. All patients was satisfied of their results. This technique used by thin thoracoscope was cosmetic and a skin incision did not need to close too small.
Endoscopy↗
Characteristics of coronary artery disease and lipoprotein abnormalities in patients with heterozygous familial hypercholesterolemia associated with diabetes mellitus or impaired glucose tolerance.
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of serum low density lipoprotein (LDL) cholesterol and premature coronary atherosclerosis. In order to elucidate the influence of abnormal glucose metabolism on the development of coronary artery disease (CAD) in FH patients, we examined the prevalence of CAD and characteristics of lipoprotein abnormalities in patients with heterozygous FH who were accompanied by diabetes mellitus (DM) or impaired glucose tolerance (IGT). The subjects of the present study were 150 patients with heterozygous FH, all over 40 years of age. Oral glucose tolerance tests demonstrated that 15 patients had DM and 27 had IGT. The combination of DM or IGT with FH was associated with a further increase in the prevalence of CAD (DM:IGT:normal glucose tolerance (N), 87:59:43%). Furthermore, the prevalence of the stenoses in the distal coronary arteries was significantly higher in the DM group than in the N group, while there was no significant difference in the prevalence of proximal and middle lesions. Serum triglyceride levels were significantly higher in the DM and IGT groups than in the N group (P < 0.01, DM versus N group; P < 0.01, IGT versus N group), while total cholesterol levels were not significantly different. When lipoproteins were analyzed by polyacrylamide gel electrophoresis, the frequency of midband appearance, which implies an increase in remnant lipoproteins, was significantly higher in the DM and IGT groups than in the N group (DM:IGT:N, 87:72:29%, P < 0.01, DM versus N group; P < 0.01, IGT versus N group). Ultracentrifugation analysis of lipoproteins revealed that intermediate density lipoprotein cholesterol was increased in DM and IGT groups compared with the N group. These data suggest that abnormal glucose metabolism may accelerate the development of CAD in FH patients due to an increase in atherogenic remnant lipoproteins in addition to high concentration of LDL. Special attention should be paid in the treatment of FH patients with impaired glucose metabolism, to avoid the advancement of coronary atherosclerosis.
Adult↗
Identification of alpha-fodrin as a candidate autoantigen in primary Sjögren's syndrome.
It is unclear whether organ-specific autoantigens are critical for the development of primary Sjögren's syndrome (SS). A 120-kilodalton organ-specific autoantigen was purified from salivary gland tissues of an NFS/sld mouse model of human SS. The amino-terminal residues were identical to those of the human cytoskeletal protein alpha-fodrin. The purified antigen induced proliferative T cell responses and production of interleukin-2 and interferon-gamma in vitro. Neonatal immunization with the 120-kilodalton antigen prevented the disease in mice. Sera from patients with SS reacted positively with purified antigen and recombinant human alpha-fodrin protein, whereas those from patients with systemic lupus erythematosus and rheumatoid arthritis did not. Thus, the immune response to 120-kilodalton alpha-fodrin could be important in the initial development of primary SS.
Amino Acid Sequence↗
Dietary effect of a symmetrical triacylglycerol, 1,3-biseicosapentaenoyl-2-gamma-linolenoyl glycerol, on fatty acid composition of guinea pigs.
The dietary effect of 1,3-biseicosapentaenoyl-2-gamma-linolenoyl glycerol (STG) on the fatty acid composition of guinea pigs was examined and compared with that of an eicosapentaenoic acid ethyl ester (EPA-E) and of a soybean oil (SBO) diet. In terms of content of plasma lipid, EPA-E had a greater hypolipidemic effect than STG. On the other hand, in terms of EPA incorporation, contents of EPA in liver lipid were almost the same in the STG and EPA-E groups. Considering that the amount of EPA administered in the EPA-E group was almost 1.5 times that of the STG group, EPA may be absorbed more effectively as the glycerol ester than as the ethyl ester in guinea pigs. In all the tissue lipids, the STG group had a higher unsaturation index (UI) than the EPA-E group even though there is a lower UI in the STG diet than the EPA-E diet. These results suggest that greater amounts of desaturase products as a whole were synthesized in the STG group than in the other two groups. The dihomo-gamma-linolenic acid/arachidonic acid (DGLA/AA) ratio in plasma total lipids in the STG group was 3.5 times that of SBO group, and the DGLA/AA ratio in the EPA-E group was half that of the SBO group. In liver lipid, the ratios of DGLA/AA and EPA/AA in the STG group were 0.687 and 0.488 (phosphatidylcholine fraction) and 0.237 and 0.752 (phosphatidylethanolamine fraction), respectively. The ratio of DGLA/AA as well as the high EPA/AA ratio obtained in the present study with the STG diet may lead to physiological alterations, including enhanced synthesis of 1- and 3-series eicosanoids.
8,11,14-Eicosatrienoic Acid↗
Increased serum remnant lipoproteins in patients with apolipoprotein E7 (apo E Suita).
Apolipoprotein (apo) E7 was originally identified by Yamamura et al. in subjects with atherosclerotic cardiovascular diseases (J. Clin. Invest. 1984;74:1229). However, the lipoprotein abnormalities associated with apo E7 phenotype have not been elucidated. In the current study, to clarify the physiological roles of apo E7, lipoprotein abnormalities were studied in 12 apo E7 heterozygotes. A total of seven subjects were hyperlipidemic and five subjects were normolipidemic. The apo E phenotype was apo E7/3 in 11 subjects and apo E7/4 in one subject. Polymerase chain reaction revealed that all of the subjects with apo E7 phenotype had the same mutation as that of apo E(Suita) as reported previously (J. Biochem. 1989;105:249). All the hyperlipidemic subjects were over 40 years of age and two of them also had and severe coronary heart disease. Ultracentrifugal analysis revealed that the cholesterol level both in very low density lipoprotein and in intermediate density lipoprotein (IDL) was substantially higher in hyperlipidemic apo E7 heterozygotes, compared with control subjects and that the IDL cholesterol was also increased even in normolipidemic apo E7 heterozygotes. Polyacrylamide gel electrophoresis of lipoproteins showed a midband, which implies the increase of remnant lipoproteins, in 11 subjects out of 12, irrespective of the presence or absence of hyperlipoproteinemia. In two cases, a broad beta pattern was observed similar to that seen in type III hyperlipoproteinemia. Dietary therapy was dramatically effective for the treatment of hyperlipidemia in patients with apo E7. These findings confirm that apo E is crucial for remnant lipoprotein metabolism and that apo E7 is related to the increase in serum remnant lipoproteins, which leads to hyperlipoproteinemia in association with obesity, aging and impaired glucose metabolism.
Adult↗