[Biogenesis and morphogenesis of vacuolar compartment].
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Cell Compartmentation↗
Biomedical subjects
Y Wada
Publications and source records attributed to Y Wada.
Vascular response to vasoactive agents in dialysed patients with chronic renal failure with and without diabetes mellitus.
Using a muscle bath technique the vascular response to KCl, noradrenaline, angiotensin II, acetylcholine, and sodium nitroprusside were evaluated in 13 patients with diabetes mellitus (DM group) and 15 nondiabetic (non-DM group) chronic renal failure patients treated with haemodialysis. There were no differences in age, duration of haemodialysis, blood pressure and the levels of plasma renin activity, noradrenaline, and parathyroid hormone between groups. After informed consent was obtained, a small piece of forearm vein was resected during the blood access surgery. The ring preparation of the blood vessel was sustained in the muscle bath filled with Krebs-Henseleit solution and the isometric tension development was recorded. All drugs produced concentration dependent responses in the ring preparations of both groups. Although there were no significant differences in Emax values for KCl- and angiotensin-II-induced contractions between groups, the value for noradrenaline in the DM group was significantly less than that in the non-DM group. Sodium nitroprusside completely relaxed the ring preparation precontracted by 10(-5) M noradrenaline. However, the response to acetylcholine in the DM group was significantly weaker than that in the non-DM group. These results suggest a reduced vascular response to noradrenaline and acetylcholine in dialysed diabetic renal failure patients, which may relate to the autonomic nervous system dysfunction.
Adult↗
[A histopathological study on the biological behavior of carcinoma in situ of the uterine cervix].
Fifty-two cases of carcinoma in situ (CIS) of the uterine cervix were examined histopathologically and compared with seventeen cases of microinvasive carcinoma of the uterine cervix (restricted to the general rules for clinical and pathological management of uterine cervical cancer of the Japan Society of Obstetrics and Gynecology) in order to investigate the influence of the patient's age on the intraepithelial extension of CIS. The results were summarized as follows. 1. There was a positive correlation between circular spread and longitudinal spread of the lesion in CIS cases. 2. There was a positive correlation between circular spread and the depth of gland involvement of the lesion in CIS cases. 3. Circular spread of the lesion in microinvasive carcinoma cases was significantly more extensive than that in CIS cases. 4. Circular spread of the lesion in microinvasive carcinoma at menopause was significantly more extensive than that in microinvasive carcinoma at sexual maturity. These results suggest that CIS has intraepithelial extensibility, and that in CIS at sexual maturity there is a higher risk of invading stroma when circular spread of the lesion becomes greater than one fourth of the whole circle in the cervix, whereas CIS at menopause is more likely to invade the stroma when the circular spread of the lesion becomes greater than half of the whole circle in the cervix. In this respect we can find the influence of the patient's age on the biological behavior of CIS of the uterine cervix.
Adult↗
[The effects of cardioplegic solution with Ni2+ upon ischemia-reperfusion in the isolated rat hearts: preliminary report].
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Animals↗
[A histopathological study on intraepithelial extensivity of carcinoma in situ of the uterine cervix in the period of sexual maturity].
To investigate intraepithelial extension of CIS, thirty-two cases of carcinoma in situ (CIS) of the uterine cervix in the period of sexual maturity were examined histopathologically and compared with ten cases of microinvasive carcinoma of the uterine cervix (restricted to Japanese criteria). The results were summarized as follows. 1) A positive correlation was found between the circular spreads and longitudinal ones in the lesion in CIS cases. 2) A positive correlation was found between circular spread and the depth of gland involvement in the lesion in CIS cases. 3) Circular spread of the lesion in microinvasive carcinoma cases was significantly more extended than that in CIS cases. These results suggest that CIS in the period of sexual maturity is intraepithelially extensive and that there is a high risk possibility of invading stroma when circular spread of the CIS lesion is greater than one fourth of the whole circle of the uterine cervix.
Adult↗
A neo-Darwinian algorithm: asymmetrical mutations due to semiconservative DNA-type replication promote evolution.
Evolution is, in a sense, to resolve optimization problems. Our neo-Darwinian algorithm based on the mechanics of inheritance and natural selection uses double-stranded DNA-type genetic information to resolve the "knap-sack problem." The algorithm with asymmetrical mutations due to semiconservative DNA-type replication most effectively resolved the problem. Our results strongly suggest that disparity in mutations caused by the asymmetric machinery of DNA replication promotes evolution, in particular of diploid organisms with a high mutation rate, in a small population, and under strong selection pressure.
Algorithms↗
Fibrinogen Mitaka II: a hereditary dysfibrinogen with defective thrombin binding caused by an A alpha Glu-11 to Gly substitution.
A new type of A alpha Glu-11 to Gly substitution has been identified in a congenitally abnormal fibrinogen, fibrinogen Mitaka II, derived from a 14-year-old female suffering from easy bruising since childhood. Plasma of the patient and fibrinogen purified therefrom were found to clot slowly by thrombin but in a normal fashion by ancrod, a thrombin-like snake venom enzyme. The ancrod-clotted fibrin gels were normally solid and turbid, whereas the thrombin-clotted gels were initially fragile and transparent but became gradually normalized during further incubation. On reverse-phase high-performance liquid chromatography, there was an additional peptide group eluted distinctly later than the corresponding normal fibrinopeptide A in the clot-liquor of the patient's samples. Sequence analysis of these aberrant peptides and isolated A alpha chains of the patient's fibrinogen showed that Glu at position 11 of the abnormal A alpha chain had been replaced by Gly. Studies using 125I-labeled thrombin showed that the binding with thrombin was evidently reduced for her fibrinogen and the aberrant fibrinopeptide A as compared with that for the normal controls, indicating that A alpha Glu-11 may be critical for the fibrinogen-thrombin interaction. Indeed, A alpha Glu-11 of fibrinogen has recently been proposed to stabilize the local conformation, including the beta-turn, and to form a salt bridge between its side-chain carboxyl group and the guanidino group of Arg-173 of thrombin based on crystallographic analyses using analogs of fibrinopeptide A complexed with thrombin (Stubb et al, Eur J Biochem 206:187, 1992 and Martin et al, J Biol Chem 267:7911, 1992).
Adolescent↗
Site-directed mutagenesis in hemoglobin: functional and structural study of the intersubunit hydrogen bond of threonine-38(C3)alpha at the alpha 1-beta 2 interface in human hemoglobin.
To clarify the functional and structural roles of Thr-38 alpha at the alpha 1-beta 2 interface, two artificial alpha-chain mutants, in which Thr-38 alpha is replaced by Ser (Hb T38 alpha S) or Val (Hb T38 alpha V), were prepared. Thr-38 alpha is one of the highly conserved amino acid residues in hemoglobins and forms a hydrogen bond to Asp-99 beta, which is a crucial residue to stabilize the T state, via a water molecule in the deoxygenated form. We investigated their oxygen binding properties together with structural consequences of the mutations by using various spectroscopic probes. Their oxygen equilibrium curves showed small changes in the oxygen binding properties. Structural probes such as ultraviolet-region derivative and oxy-minus-deoxy difference spectra, resonance Raman scattering, and 1H-NMR spectra also indicated that the oxy and deoxy forms of these mutants show spectra characteristic of the R and T states, respectively, and the R-T transition is not very disturbed. The present structural and functional data of the mutants imply that the hydrogen bond between Thr-38 alpha and Asp-99 beta does not play a key role in stabilizing the deoxy T structure, which is in sharp contrast to the role of the hydrogen bond between Tyr-42 alpha and Asp-99 beta, and suggest that the interactions via the intersubunit hydrogen bonds are highly site-specific, depending on the amino acid residue which participates in them.
Globins↗
A synthetic model of collagen structure taken from bovine macrophage scavenger receptor.
A putative collagen structure from macrophage scavenger receptors binds to a wide range of ligands. In order to elucidate the ligand's binding mode, this collagen structure was constructed using short peptides. This was accomplished by the reaction of a tri-bromoacetylated branched peptide with a purified unprotected 25-residue peptide, which contained Cys, 4 repeats of triplet, Gly-Pro-Hyp, and 12 residues from the bovine of the N-terminus cross-linked tripeptide show that it forms a collagen structure below 10 degrees C and an extended structure at high temperature with a midpoint of 20 degrees C.
Amino Acid Sequence↗
Molecular cloning of a cDNA encoding human histidase.
We isolated overlapping cDNA clones encoding human histidase (histidine ammonia-lyase) from a human lambda gt10 library. The cDNA predicted a 657 amino acid protein of 72,651 Da. The human histadase amino acid sequence was 93% conserved with both rat and mouse histidase sequences, including four N-glycosylation consensus sites.
Amino Acid Metabolism, Inborn Errors↗
Increase in housing temperature can alleviate decrease in white blood cell counts after energy restriction in C57BL/6 female mice.
White blood cell (WBC) counts decrease after energy restriction (ER) in both rodents and humans. ER reduces cellular proliferation rates in various organs of rodents. Increases in housing temperatures can cancel this inhibitory effect of ER. We investigated whether a high housing temperature can alleviate decreases in WBC counts after ER, since peripheral WBC counts at basal levels are considered to represent cellular proliferation rates in the bone marrow. C57BL/6 female mice were allocated to three groups: the control (397 kJ/week), the ER (176 kJ/week) and the ER housed-in-incubator group (ERI: 134 kJ/week). The former two groups were housed at 21-23 degrees C and the third group was housed at 30 degrees C. At 4 and 13 months of age, WBC counts were significantly lower in ER or ERI mice than in control mice. WBC counts, however, were significantly higher in ERI mice (194%) than in ER mice at 13 months of age. A high housing temperature was proved to antagonize the effect of ER on WBC counts, as it antagonizes suppressive effects of ER on cellular proliferation rates in various organs.
Animals↗
Intra-hippocampal injection of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) inhibits partial and generalized seizures induced by kindling stimulation in cats.
This study assessed the effects of microinjections of a serotonin (5-HT) 1A agonist, 8-OH-DPAT, into the feline hippocampus (HIP) on seizure response induced by electrical stimulation of this region. Intra-HIP injection of 8-OH-DPAT (10 nmol) produced a significant elevation in the afterdischarge threshold of partial HIP seizures, with a significant reduction in the duration of focal afterdischarge. Similarly, microinjection of 8-OH-DPAT at the same dose significantly raised the seizure threshold for eliciting generalized seizures in HIP-kindled cats. The present results demonstrate that focally applied 8-OH-DPAT possesses a potent anticonvulsant action, and provide further evidence for the inhibitory role of 5-HT1A receptors in the generation of HIP seizures.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
A new type of congenital dysfibrinogen, fibrinogen Bremen, with an A alpha Gly-17 to Val substitution associated with hemorrhagic diathesis and delayed wound healing.
We have identified a new type of A alpha Gly-17 to Val substitution in a congenital dysfibrinogen, fibrinogen Bremen, derived from a 15-year-old boy having manifested easy bruising and delayed wound healing. The functional abnormality was characterized by altered fibrin monomer polymerization, which became evident by increasing the salt concentration and pH. A synthetic tetrapeptide with a sequence of the amino-terminal segment of normal fibrin alpha-chain, Gly-Pro-Arg-Val, substantially inhibited polymerization of both normal and the patient-derived fibrin monomers. A synthetic tetrapeptide with the Bremen type sequence of Val-Pro-Arg-Val inhibited polymerization of the patient's fibrin monomers partially at a peptide: fibrin monomer molar ratio of 4,000:1, and that of normal one at a much higher ratio of 10,000:1. Likewise, a synthetic peptide Ala-Pro-Arg-Val with a replacement of the Gly residue by another aliphatic amino acid Ala inhibited similarly the patient's fibrin monomer polymerization. Thus, the hypothetical two-pronged socket-like structure consisting of the alpha-amino group of the amino-terminal Gly and the guanidino group of an Arg at position 3 of the normal fibrin alpha-chain seems to be restored considerably in the mutant fibrin alpha-chain at low ionic strengths and pH's, despite the replacement of the amino-terminal Gly by another aliphatic amino acid Val.
Adolescent↗
Hereditary nodular heterotopia accompanied by mega cisterna magna.
This is the first report of hereditary nodular heterotopia accompanied by mega cisterna magna. Magnetic resonance imaging documented multiple bilateral subependymal nodules, which were isointense to gray matter. This disease entity is considered a dominant trait, since the mother and two daughters, half-sisters, were affected.
Adult↗
Synthesis of the laminara-oligosaccharide methyl beta-glycosides of dp 3-8.
Ethyl 2,3,4,6-tetra-O-acetyl-1-thio-alpha-D-glucopyranoside has been prepared in a good yield by anomerization of the corresponding beta-thioglucoside with tin(IV) chloride and transformed, in three steps, into ethyl 2-O-benzoyl-4,6-O-benzylidene-1-thio-alpha-D-glucopyranoside (18). Chloroacetylation of 18, followed by treatment of the product with chlorine gave crystalline 2-O-benzoyl-4,6-O-benzylidene-3-O-chloroacetyl-beta-D-glucopyranosyl chloride (20). This was coupled with methanol in the presence of silver carbonate-silver perchlorate and the product was O-dechloroacetylated to afford methyl 2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranoside (22). Silver triflate-promoted glucosylation of 18 with 20 gave a beta-(1-->3)-linked disaccharide derivative, reaction of which with chlorine yielded crystalline O-(2-O-benzoyl-4,6-O-benzylidene-3-O-chloroacetyl-beta-D-glucopyranosyl) - (1-->3)-2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl chloride (24). Likewise, condensation of 22 with 20 gave a beta-(1-->3)-linked disaccharide glycoside, which was partially deprotected to give methyl O-(2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl)-(1-->3)-2-O-benz oyl- 4,6-O-benzylidene-beta-D-glucopyranoside (26). The methyl beta-glycosides of a homologous series of (1-->3)-linked beta-D-gluco-oligosaccharides from the tri- to the octa-saccharide have been synthesized in a blockwise manner by using 22 and 26 as the glycosyl acceptors, 24 as the disaccharide donor, and silver triflate as the promoter.
Carbohydrate Conformation↗
Structure, organization, and chromosomal mapping of the human macrophage scavenger receptor gene.
Macrophage scavenger receptors (MSR) mediate the binding, internalization, and processing of a wide range of negatively charged macromolecules. Functional MSR are trimers of two C-terminally different subunits that contain six functional domains. We have cloned an 80-kilobase human MSR gene and localized it to band p22 on chromosome 8 by fluorescent in situ hybridization and by genetic linkage using three common restriction fragment length polymorphisms. The human MSR gene consists of 11 exons, and two types of mRNAs are generated by alternative splicing from exon 8 to either exon 9 (type II) or to exons 10 and 11 (type I). The promoter has a 23-base pair inverted repeat with homology to the T cell element. Exon 1 encodes the 5'-untranslated region followed by a 12-kilobase intron which separates the transcription initiation and the translation initiation sites. Exon 2 encodes a cytoplasmic domain, exon 3, a transmembrane domain, exons 4 and 5, an alpha-helical coiled-coil, and exons 6-8, a collagen-like domain. The position of the gap in the coiled coil structure corresponds to the junction of exons 4 and 5. These results show that the human MSR gene consists of a mosaic of exons that encodes the functional domains. Furthermore, the specific arrangement of exons played a role in determining the structural characteristics of functional domains.
Amino Acid Sequence↗
Charged collagen structure mediates the recognition of negatively charged macromolecules by macrophage scavenger receptors.
Macrophage scavenger receptors mediate the recognition of a wide range of negatively charged macromolecules including modified low density lipoproteins (LDL). Truncated bovine receptors lacking residues 330-342, which include the conserved lysine cluster of a collagen-like domain, were unable to degrade modified LDL in spite of their expression on the cell surface. Substitution of lysine 337 into alanine abolished the acetyl-LDL degradation and binding at 37 degrees C, but did not abolish the 4 degrees C binding. In contrast, substitution of more than 2 lysines in this region are needed to abolish the oxidized LDL degradation and 37 degrees C binding. Based on computational modeling of this domain, we propose that a "charged collagen" structure containing a lysine cluster forms a positively charged groove which specifically interacts with negatively charged ligands.
Amino Acid Sequence↗
Two-dimensional elution map of GalNAc-containing N-linked oligosaccharides.
We have previously published a two-dimensional (2-D) mapping technique for N-linked oligosaccharides using pyridylaminated derivatives (PA-oligosaccharides) (N. Tomiya et al. Anal. Biochem. 171, 73-90, 1988). We now report an extension of this method to GalNAc-containing N-linked oligosaccharides. The new 2-D map was prepared from the elution data of 40 different GalNAc-containing oligosaccharides, 16 of which were obtained directly from human urinary kallidinogenase by digestion with glycopeptidase A. The other 24 oligosaccharides were derived by subsequent digestion of the 16 original oligosaccharides with beta-galactosidase or alpha-fucosidase. Each of the 40 oligosaccharide derivatives was separated by high-performance liquid chromatography using ODS-silica and amide-silica columns. The 2-D map constructed by plotting elution position of each oligosaccharide (expressed in terms of glucose units) can be useful as such in delineating the structure of an unknown oligosaccharide by direct placement of its elution positions in the 2-D map. Multiple regression analysis of the data as performed previously yielded parameters related to the contribution of each component monosaccharide unit to the elution profile. The best results were obtained when the GalNAc-containing PA-oligosaccharides were classified into an F-series (those containing Fuc alpha 6GlcNAc-PA) and a Z-series (all others), based on our previous classification method. These calculated values are useful in predicting oligosaccharide structure from known elution values as well as to predict elution volumn from a known structure. The structure of a minor GalNAc-containing oligosaccharide in human urinary kallidinogenase was elucidated using these newly calculated values.
Acetylgalactosamine↗