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Biomedical subjects

K Kitajima

Publications and source records attributed to K Kitajima.

At least 109 records · Page 6Linked to original sources

Organogenesis of the liver, thymus and spleen is affected in jumonji mutant mice.

The recessive mutant mouse jumonji (jmj), obtained by a gene trap strategy, shows neural tube defects in approximately half of homozygotes with a Balb/cA and 129/Ola mixed background. Here, we show that no neural tube defects are observed with a Balb/cA background. We also found hypoplasia of the liver, thymus and spleen with full penetrance with a Balb/cA background. In the livers of homozygous embryos we found excessive cell death in the peripheral region. In both the thymus and spleen, the accumulation of hematopoietic cells is affected in mutant embryos. These phenotypes were also observed with C57BL/6J and DBA/2J backgrounds, suggesting that the jmj gene plays an essential role in the organogenesis of these tissues.

Animals↗

Proton NMR study of triantennary complex type N-linked glycan chains: assignment of proton chemical shifts of the beta-Man residue in a basic unit of the triantennary glycan chain having a GlcNAc beta 1-->6 Man alpha 1-->6 Man beta-->sequence.

The chemical shifts of ring protons of the beta-Man residue in a triantennary complex type N-linked glycan chain having a GlcNAc beta 1-->6(GlcNAc beta 1-->2)Man alpha 1-->6 Man beta sequence were unambiguously determined by two-dimensional proton nuclear magnetic resonance (1H-NMR) spectroscopic methods. The chemical shift of H4 (3.84 ppm) of the beta-Man residue was for the first time revealed to be different from those (approximately 3.77 ppm) of biantennary and alternative type of triantennary glycans having a GlcNAc beta 1-->2 Man alpha 1-->6 Man beta sequence, but quite close to that (3.86 ppm) of a pentaantennary glycan containing a GlcNAc beta 1-->6 residue on the Man alpha 1-->6 Man beta sequence. Thus, the addition of GlcNAc beta 1-->6 residue on the Man-4' residue, whose formation is catalyzed by GlcNAc transferase V, is considered to cause a down-field shift of beta-Man H4 in the complex-type N-glycan chains. One possible explanation of this phenomenon is that the conformation of Man alpha 1-->6 arm is folded back toward the proximal core region, as is the case with the complex-type N-glycan chains with the bisecting GlcNAc residue.

Acetylglucosamine↗

Occurrence of terminal alpha 2-->8-linked disialylated poly-N-acetyllactosamine chains with Le(X) and I antigenic glycotopes in tetraantennary arms of an N-linked glycoprotein isolated from rainbow trout ovarian fluid.

The Pronase digestion of a 54K glycoprotein present in ovarian fluid of rainbow trout yielded a major glycopeptide. Carbohydrate compositional analysis revealed that this glycopeptide was likely to possess a single large N-glycan chain having low molecular weight oligomers of N-acetylneuraminic acid (oligoNeu5Ac). Structural studies of this glycopeptide revealed novel alpha 2-->8-linked disialylated poly-N-acetyllactosamine chains with Le(X) and I antigenic determinants on the N-linked tetraantennary core glycan. In our recent studies (Kitazume,S., Kitajima,K., Inoue,S., Inoue,Y. and Troy,F.A. (1994) J. Biol. Chem. 269, 10330-10340) we presented evidence that synthesis of alpha 2-->8-linked polysialic acid (polySia) chains is a two-step process in which chain initiation is catalyzed by an alpha 2-->8-sialyltransferase (alpha 2-->8-ST; initiase) that catalyzes synthesis of the first Sia alpha 2-->8-linkage, forming the disialic acid (diSia) unit, Sia alpha 2-->8-Sia alpha 2-->6-Gal-. Chain polymerization is then postulated to be catalyzed by a second enzyme, an alpha 2-->8-polyST ("polymerase") that converts the diSia units to polySia chains. The present structural studies leading to the discovery of alpha 2-->8-linked disialylated units that terminate poly-N-acetyllactosamine chains in an N-linked glycoprotein is further evidence in support of our hypothesis that more than one sialyltransferase activity is required for polySia chain synthesis and polymerization.

Animals↗

REM sleep motor dysfunction in multiple system atrophy: with special emphasis on sleep talk as its early clinical manifestation.

Various neurodegenerative diseases involving brainstem structures as one of the main pathological lesions are reported to be associated with REM sleep behaviour disorder. Full blown REM sleep behaviour disorder can be diagnosed clinically, but REM sleep motor dysfunction, a pathophysiological basis of REM sleep behaviour disorder, is difficult to detect without all night polysomnography. Twenty one consecutive patients with multiple system atrophy with no complaints of nocturnal abnormal behaviours were clinically evaluated to determine the presence of sleep related symptoms. All night polysomnography with video monitoring was performed to investigate REM sleep characteristics and patients' behaviours. In 85.7% (18 of 21) of the patients' sleep talk started or increased around or after the clinical onset of the primary diseases. REM sleep without atonia occupied more than 15% (16.2%-100%) of the REM sleep time in all but one patient. In 90.5% (19 of 21) of patients, motor events such as sleep talk and various combinations of craniofacial, orofacial, or limb movements occurred at various frequencies mostly during REM sleep without atonia. In patients with multiple system atrophy, REM sleep motor dysfunction is a common polysomnographic finding which is otherwise overlooked, and sleep talk may be its early clinical manifestation.

Aged↗

Effects of transglottal pressure change on fundamental frequency of phonation: preliminary evaluation of the effect of intraoral pressure change.

The effect of transglottal pressure on the fundamental frequency of phonation was investigated in 14 subjects (12 adults and 2 children). A sudden change in intra-oral pressure was produced during sustained phonation. The effects of this pressure change were not monotonic, even within the modal register (around the upper end of the speaking range). The physical properties of the vocal folds related to the cricothyroid and thyroarytenoid muscles seemed to be important.

Adult↗

[Influence of transglottal pressure on vocal fundamental frequency changes with stiffness of vocal folds].

We have described the influence (dF/dP) of transglottal pressure on vocal fundamental frequency (F0). It was previously reported that dF/dP varied with the stiffness of the vocal folds, and that the vocal fold membrane when dry was stiffer than when wet. Normal subjects were injected with atropine sulfate in order to dry their larynx, as a model of stiffer-than-normal vocal folds. Transglottal pressure changes during sustained phonation were applied by partially closing a shutter valve mounted on a mouthpiece. Both before and after atropine sulfate injection, the values of dF/dP, in modal register, decreased and increased as F0 increased, and the smallest values of dF/dP were negative in all subjects. The absolute values of both the largest and smallest dF/dP in subjects with atropine sulfate were smaller than those in normal subjects. These finding indicated that dF/dP is correlated with the stiffness of the vocal folds.

Adult↗

[Differences in temporal bone development in various ear diseases].

To investigate the differences in temporal bone development in various ear diseases--bilateral Meniere's disease (n = 13), unilateral Meniere's disease (n = 41), unilateral chronic otitis media (COM) (n = 25), temporal bone fracture (n = 9) and otosclerosis (n = 12)--the following 4 distances on a temporal bone CT slice encompassing the lateral semicircular canal (LSC) were measured by using the NIH Image program. These distances included the minimal distance between the posterior semicircular canal (PSC) and the posterior petrous surface (PPS) (P-P distance), the minimal distance between the PSC and the LSC (P-L distance), the minimal distance between the vestibule and the PPS (V-P distance) and the minimal distance between the PSC and the anterior margin of the sigmoid sinus (P-S distance). Both the P-P and V-P distances showed significant differences among the ear diseases, but the P-L and P-S distance did not. Meniere's disease showed significantly shorter P-P and V-P distance especially in bilateral Meniere's disease than those in COM and otosclerosis (p < 0.05). Affected ears in unilateral Meniere's disease showed a shorter P-P distance than non-affected ears (p < 0.01). In contrast, both ears with otosclerosis showed significantly longer P-P and V-P distances than those in Meniere's disease, COM (p < 0.01) and temporal bone fracture (p < 0.05). COM and temporal bone fracture showed intermediate P-P and V-P distances, without a difference between the affected and non-affected ears. In conclusion, the development of the posterior part of the temporal bone is reduced in Meniere's disease and greatly increased in otosclerosis. These findings by CT may be useful for diagnosing ear diseases.

Ear Diseases↗

[Clinical features of Sjögren syndrome].

Between 1985 and 1995, 134 patients presented to our clinic with complaints of either dry mouth, decreased salivary flow or salivary gland swelling of unknown origin. These patients were diagnosed retrospectively based on the criteria established by the Sjögren's disease research committee (1977), and 30 patients were definitively diagnosed with Sjögren's disease while 23 were considered suspect. The gender distribution of these 30 patients was 25 female (83%) and 5 male (17%). The average patient age was 55.8 years for females and 42.6 years for males. Of 30 patients, 10 (33.3%) had only sicca syndrome and the other 20 (66.7%) had various complications such as collagen diseases, autoimmune diseases, and malignant lymphoid infiltration. Subjects included 14 cases of rheumatoid arthritis (RA), 1 case of systemic lupus erythematosus (SLE), 1 case of RA with periarteritis nodosa (PN), 1 case of progressive systemic sclerosis (PSS) with SLE, 1 case of PSS with Hashimoto disease, 1 case of malignant lymphoma and 1 case of RA with Waldenström's macroglobulinemia. Positive blood tests showed a relatively high incidence of elevated erythrocyte sedimentation ratios (ESR) (75%), elevated IgG levels (69.2%), positive anti-nuclear antibody (52.3%), positive anti SS A antibody (75%) and positive anti-SS B antibody (50%).

Adolescent↗

[Two cases of tracheal injuries secondary to blunt trauma].

We present two cases of injury to the cervical trachea and the tracheal bifurcation due to blunt trauma. A 20-year-old man sustained complete disruption of the cervical trachea during a traffic accident. He underwent end-to-end anastomosis of the disrupted trachea. Nevertheless, 3 weeks after the initial surgery, tracheostomy was required because of suture failure. Two months after the second procedure, he underwent closure of the tracheostoma. Granulation developed temporarily, but diminished thereafter. The second case was a 14-year-old boy. He sustained a longitudinal laceration about 3 cm from the tracheal over the membranous portion during a traffic accident. The laceration was successfully repaired by interrupted sutures with absorbable materials. Our experiences emphasize the importance of debridement of the injured cartilageous portion during treatment of tracheal injury due to blunt trauma and the difficulty in managing complete disruption of the cervical trachea with bilateral paralysis of the recurrent nerve.

Accidents, Traffic↗

Characterization of the major core structures of the alpha2-->8-linked polysialic acid-containing glycan chains present in neural cell adhesion molecule in embryonic chick brains.

To gain more insight into the possible functional significance of the core glycan chain(s) on which polysialylation takes place in polysialic acid (poly-Sia)-containing glycoproteins, the structure of the core glycans in the embryonic form of chick brain neural cell adhesion molecule (N-CAM) were examined using chemical and instrumental techniques. The following new structural features, which had not been reported by the early pioneering study by Finne (Finne, J. (1982) J. Biol. Chem. 257, 11966-11970), were revealed (Structure I). (i) Two distinct types of multiantennary N-linked glycans, i.e. tri- and tetra-antennary structures, are present; (ii) an alpha1-->6-linked fucosyl residue is attached to the proximal GlcNAc residue of the di-N-acetylchitobiosyl unit; (iii) that the action of GlcNAc-transferase V, which catalyzes the attachment of the beta-(1-->6)-linked GlcNAc residue on the (1-->6)-alpha-linked mannose (Man) arm, appears to be essential for polysialylation to occur on the core glycan chain is suggested by the fact that the Man residue alpha1-->6-linked to the beta-linked Man residue is invariably 2,6-di-O-substituted by the GlcNAc residue; (iv) both type 1 (Galbeta1-->3GlcNAc) and type 2 (Galbeta1-->4 GlcNAc) sequences are present in the peripheral portion of the core glycan structure. An extended form of the type 2 chain, i.e. Galbeta1-->4GlcNAcbeta1-->3Galbeta1-->4GlcNAc, is also expressed on the (1-->3)- and (1-->6)-alpha-linked Man arms; (v) on average about 1.4 mol of sulfate is attached to the type 2 N-acetyllactosamine chain(s), where in the extended form the sulfate group is probably substituted at the O-3 position of the outmost GlcNAc residue, i.e. Galbeta1-->4(HSO3-->3)GlcNAcbeta1-->3Galbeta1--> 4GlcNAcbeta1-->Man. It is possible that the unusual structural features identified in this study might play a role in the initiation of polysialylation and our data should facilitate future research regarding the signals that control polysialylation.

Acetylation↗

Identification of 2-keto-3-deoxy-D-glycero--galactonononic acid (KDN, deaminoneuraminic acid) residues in mammalian tissues and human lung carcinoma cells. Chemical evidence of the occurrence of KDN glycoconjugates in mammals.

Since the discovery of KDN glycoprotein in 1986, the occurrence of KDN (= 2-keto-3-deoxy-D-glycero-D-galactonononic acid) glycan chains has been reported for different organisms ranging from bacteria to lower vertebrates, including amphibians and fish. Recently, the presence of alpha2-->8-linked oligo/polyKDN groups in mammalian tissues was shown by immunohistochemical and immunoblotting methods. In this communication we report the detection and quantitation of the KDN residues in glycoprotein and glycolipid fractions of rat tissues and human lung cancer cell lines by a highly sensitive fluorometric high-performance liquid chromatography (HPLC) method. We now provide unequivocal chemical proof of the occurrence of KDN in mammals by isolation of KDN from pig submaxillary gland and by structural assignment using chemical methods including fast atom bombardment-mass spectrometry, fluorescence-assisted HPLC analysis, gas-liquid chromatography, and 1H NMR spectroscopy.

Adenocarcinoma↗

Morphological and electrophysiological properties of ACCx nociceptive neurons in rats.

A total of 33 neurons with cutaneous receptive fields were recorded from the anterior cingulate cortex (ACCx) and successfully injected with neurobiotin. All neurons were in area 24 of the ACCx. Neurons from the ACCx had large receptive fields (RFs), usually bilateral, and some had RFs covering the whole body surface. Most of the neurons were in the deep laminae and had a pyramidal soma with thick apical dendrites and many spines. Thirteen of 33 neurons were classified as pyramidal nociceptive specific (NS) neurons and 12 as noxious-tap neurons, 3 neurons received inhibitory input and were in lamina V. Two non-pyramidal noxious-tap neurons were located in lamina V and 1 pyramidal noxious-tap neuron was located in lamina VI, and 2 pyramidal NS neurons were in lamina III. Axon collaterals of NS neurons were mainly distributed around the soma, whereas those of noxious-tap neurons were also distributed far from the soma. A large number of varicosities were observed on the axon collaterals of both NS and noxious-tap neurons. Our results suggest that NS neurons in the ACCx send information locally to the vicinity of the soma, while noxious-tap neurons send information to a wider area of the ACCx.

Animals↗

Occurrence and structural analysis of highly sulfated multiantennary N-linked glycan chains derived from a fertilization-associated carbohydrate-rich glycoprotein in unfertilized eggs of Tribolodon hakonensis.

This study represents the first detailed investigation of the nature of highly sulfated (keratan-sulfate-like) complex-type asparagine-linked glycans having a tetraantennary core structure and shows the effectiveness of fast-atom-bombardment mass spectrometric (FAB-MS) methods incorporating derivatization and mild methanolysis for analyzing such complex types of sulfated glycans. The structure of the N-glycan chains was unambiguously established by a combination of compositional analysis, methylation analysis, mild methanolysis for desulfation, hydrazinolysis/nitrous acid deamination, enzymatic (endo-beta-galactosidase and peptide:N-glycosidase F) digestions, and instrumental analyses (1H-NMR spectroscopy and FAB-MS) which revealed the novel repeating sulfated carbohydrate sequences, +/- Gal beta 1-->4Gal beta 1[-->(HSO3-->6)GlcNAc beta 1-->3(+/- Gal beta 1-->4)Gal beta 1]n--> (see Structure I; p + q + r + s approximately 14). This sequence is unique in: (a) the skeletal structure is similar to that of keratan sulfate but is completely devoid of 6-O-sulfated Gal residues and (b) the presence of branched Gal residues in the sequence -->4GlcNAc beta 1-->3(Gal beta 1-->4)Gal beta 1-->. [formula: see text]

Animals↗

Second zinc finger mutants of thyroid hormone receptor selectively preserve DNA binding and heterodimerization but eliminate transcriptional activation.

Transcriptional regulation by thyroid hormone is mediated through its nuclear receptors (TRs), which bind to target responsive elements as homodimers or as heterodimers with 9-cis retinoic acid receptors (RXRs). We examined the dimerization and functional properties of TRs containing mutations in the first and second zinc finger regions of the DNA binding domain. Interestingly, a mutation (R158G) in the loop of second zinc finger, or a chimeric mutant in which the second zinc finger of the glucocorticoid receptor (GR) was substituted for that of the TR, did not form homodimer, but still bound as a heterodimer with RXR alpha. Despite the presence of heterodimer formation, these mutants were functionally inactive in transfection assays. We conclude that sequences within the loop of the second zinc finger may play an important role in stability in vivo or transcriptional activation of the TR.

Amino Acid Sequence↗

Occurrence of poly(alpha2,8-deaminoneuraminic acid) in mammalian tissues: widespread and developmentally regulated but highly selective expression on glycoproteins.

In tissues of higher organisms homopolymers of alpha2,8-linked N-acetylneuraminic acid can be found as a posttranslational modification on selected proteins. We report here the discovery of homopolymers of alpha2,8-linked deaminoneuraminic acid [poly(alpha2,8-KDN)] in various tissues derived from all three germ layers in vertebrates including mammals. The monoclonal antibody kdn8kdn in conjunction with a bacterial KDNase permitted the detection of poly(alpha2,8-KDN) by immunohistochemistry and immunoblotting. Further evidence for the existence of poly(alpha2,8-KDN) was obtained by gas/liquid chromatography. The poly(alpha2,8-KDN) glycan was detectable in all tissues studied with the exception of mucus-producing cells present in various organs, the extracellular matrix, and basement membranes. However, in certain organs such as muscle, kidney, lung, and brain its expression was developmentally regulated. Despite its widespread tissue distribution, the poly(alpha2,8-KDN) glycan was detected on a single 150-kDa glycoprotein except for a single >350-kDa glycoprotein in kidney, which makes it most distinctive among polysialic acids. The ubiquitous yet selective expression may be indicative of a general function of the poly(alpha2,8-KDN)-bearing glycoproteins.

Animals↗

The occurrence of novel 9-O-sulfated N-glycolylneuraminic acid-capped alpha2-->5-Oglycolyl-linked oligo/polyNeu5Gc chains in sea urchin egg cell surface glycoprotein. Identification of a new chain termination signal for polysialyltransferase.

We report the isolation and structural characterization of an oligo/polysialic acid-containing glycopeptide fraction (designated ESP-Sia) prepared from the egg cell surface complex of the sea urchin, Hemicentrotus pulcherrimus, by exhaustive pronase treatment. The carbohydrate chains isolated from ESP-Sia were shown to consist of O-linked oligo/polysialic acid-containing glycan units and N-linked carbohydrate chains. The present studies have revealed that the O-linked oligo/polysialic acid-containing glycan chains derived from the ESP-Sia were similar to those present in egg jelly coat polysialylated glycoprotein in being composed of tandem repeats of N-glycolylneuraminic acid (Neu5Gc) glycosidically linked in a novel fashion through the glycolyl group, (-->5-OglycolylNeu5Gcalpha2-->)n. However, they differ from the egg jelly coat in two key respects. First, the average degree of polymerization of the oligo/polysialic acid chains of ESP-Sia is only 3; a value far lower than that found in the jelly coat glycoprotein (average degree of polymerization was about 20). Second, ESP-Sia is uniquely characterized by the presence of 9-O-sulfated N-glycolylneuraminic acid (Neu5Gc9HSO3) residues at the nonreducing termini of the (-->5-OglycolylNeu5Gcalpha 2-->)n chains. The terminal sialyl residues in the Neu5Gc9HSO3 alpha2-->(-->5-OglycolylNeu5Gcalpha2-->)n chains were totally resistant to exosialidases. The discovery of Neu5Gc9HSO3 as the nonreducing terminal residue of oligo/poly(-->5-OglycolylNeu5Gcalpha 2-->) group is especially noteworthy in that Neu5Gc9HSO3 appears to be of limited distribution among glycoconjugates. Following the earlier discovery of oligo/polysialic acid chains capped with KDN, i.e. KDN alpha2-->(-->8Neu5Gcalpha2-->)n, found in rainbow trout egg polysialoglycoproteins, it now appears that the sulfated Neu5Gc can serve a similar capping function.

Acetylation↗

Substrate specificity of rainbow trout testis CMP-3-deoxy-D-glycero-D-galacto-nonulosonic acid (CMP-Kdn) synthetase: kinetic studies of the reaction of natural and synthetic analogues of nonulosonic acid catalyzed by CMP-Kdn synthetase.

In this report we present kinetic data of the activation reaction of several synthetic 3-deoxy-D-glycero-D-galacto-nonulosonic acid (Kdn) and N-acetylneuraminic acid (Neu5Ac) analogues catalyzed by the rainbow trout testis CMP-Kdn synthetase. This enzyme showed broad substrate specificity in terms of substitutions at C4 or C5 position of Kdn and Neu5Ac. In contrast, calf brain CMP-N-acylneuraminic acid synthetase had narrow substrate specificity, being active only on various N-acyl analogues of Neu5Ac and only slightly active on Kdn derivatives. Usefulness of the trout testis enzyme for synthesis of various CMP-sialate analogues, which could be donor substrates for sialyltransferases, was demonstrated.

Animals↗